@article{giurgis_mccann-deshazer_gadsby_poole_2024, title={Impact of progesterone signaling on tumor necrosis factor-alpha synthesis by luteal macrophages}, volume={102}, ISSN={["1525-3163"]}, DOI={10.1093/jas/skae019.066}, abstractNote={Abstract}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Giurgis, Mariam and McCann-Deshazer, Madison and Gadsby, John E. and Poole, Daniel H.}, year={2024}, month={Mar}, pages={55–56} } @article{beachler_gracz_morgan_bembenek bailey_borst_ellis_von dollen_lyle_nebel_andrews_et al._2021, title={Plasma metabolomic profiling of healthy pregnant mares and mares with experimentally induced placentitis}, volume={53}, ISSN={["2042-3306"]}, DOI={10.1111/evj.13262}, abstractNote={Abstract}, number={1}, journal={Equine Veterinary Journal}, author={Beachler, T.M. and Gracz, H.S. and Morgan, D.R. and Bembenek Bailey, S.A. and Borst, L. and Ellis, K.E. and Von Dollen, K.A. and Lyle, S.K. and Nebel, A.M. and Andrews, N.C. and et al.}, year={2021}, month={Jan}, pages={85–93} } @article{beachler_bailey_gracz_morgan_von dollen_ellis_gadsby_lyle_2020, title={Metabolomic Profile of Allantoic and Amniotic Fluid in Late-term Gestational Mares Characterized by H-1-nuclear Magnetic Resonance Spectroscopy}, volume={94}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2020.103235}, abstractNote={The amniotic and allantoic fluid compartments in the mare serve essential roles throughout pregnancy and parturition. Although the global metabolomic profile of amniotic fluid in women has been extensively characterized, current data for equine fetal fluids are limited. Therefore, the goal of this study was to characterize the global metabolomic profile of equine allantoic and amniotic fluid through nuclear magnetic resonance spectroscopy. Fetal fluids were collected between 270 and 295 days of gestation from 12 pregnancies through ultrasound-guided transabdominal puncture. A total of 24 samples (n = 10 allantoic fluid; n = 9 amniotic fluid; n = 5 admixed fluid) were analyzed by one-dimensional proton (1H) and two-dimensional (1H-13 C) nuclear magnetic resonance spectroscopy. Metabolites were integrated and compared between fluid types using a Kruskal–Wallis test at P < .05 significance. A total of 28 distinct metabolites were found in allantoic and admixed fluid, whereas 23 metabolites were identified in amniotic fluid. Allantoic fluid contained significant elevations (P < .05) in the metabolites betaine, creatine, creatinine, citrate, histidine, nitrophenol, tryptophan, π-methylhistidine, and unknown metabolite #1 compared with amniotic fluid, whereas amniotic fluid contained statistically increased concentrations of the metabolite lactate compared with allantoic fluid (P = .003).}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Beachler, Theresa M. and Bailey, C. Scott and Gracz, Hanna S. and Morgan, Davic R. and Von Dollen, Karen A. and Ellis, Katey E. and Gadsby, John E. and Lyle, Sara K.}, year={2020}, month={Nov} } @article{beachler_gracz_long_borst_morgan_nebel_andrews_koipillai_frable_bailey_et al._2019, title={Allantoic Metabolites, Progesterone, and Estradiol-17 beta Remain Unchanged After Infection in an Experimental Model of Equine Ascending Placentitis}, volume={73}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2018.11.014}, abstractNote={The objective of this study was to characterize the metabolomic profile of equine allantoic fluid in the pregnant mare with and without experimentally induced ascending placentitis with the goal of identifying biomarkers of this disease. We compared the onset of metabolomic changes with common modalities for diagnosis of ascending placentitis, including measurement of the combined thickness of the uterus and placenta (CTUP), hormonal profiling, and measurement of serum acute phase proteins. Ten pregnant pony mares were randomly divided into two groups: five healthy control mares (CONT) and five mares induced to develop ascending placentitis (PLAC) via inoculation with Streptococcus equi subsp. zooepidemicus bacteria at Days 280–285 of gestation. Allantoic fluid, whole blood, and serum were collected from both groups at 270–275 days of gestation and at the following time points postinoculation: 4 hours, Days 2, 4, 6, and 10. Differences between groups in identified metabolites, progesterone, estradiol-17β, lactate, and serum amyloid A (SAA) were assessed using an analysis of variance with repeated measures. A total of 27 metabolites were identified in allantoic fluid. No differences were detected between groups at any time point (P > .05) for any identified metabolite, progesterone, estradiol-17β, or lactate concentrations. Significant elevations in CTUP (P = .003) and SAA (P = .0001) were detected by Days 4 and 6 postinoculation, respectively. The results of this study established a database of equine allantoic fluid metabolites and confirmed the utility of uteroplacental ultrasound for detection of placentitis before the onset of hematologic changes.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Beachler, Theresa and Gracz, Hanna and Long, Nathan M. and Borst, Luke and Morgan, David and Nebel, Amber and Andrews, Natalie and Koipillai, Joanna and Frable, Samantha and Bailey, Stasia Bembenek and et al.}, year={2019}, month={Feb}, pages={95–105} } @article{gadsby_frandsen_chang_celestino_tucker_poole_2019, title={Progesterone inhibits cytokine/TNF-α production by porcine CL macrophages via the genomic progesterone receptor}, volume={12}, ISSN={0739-7240}, url={http://dx.doi.org/10.1016/j.domaniend.2019.106426}, DOI={10.1016/j.domaniend.2019.106426}, abstractNote={In pigs, luteolytic sensitivity to PGF-2α (=LS) is delayed until d 13 of the estrous cycle. While the control of LS is unknown, it is temporally associated with macrophage (MAC; which secretes tumor necrosis factor [TNF]-α) infiltration into the corpora lutea (CL), and previous studies have shown that TNF-α induces LS in porcine luteal cells (LCs) in culture. This study was designed to explore the control of LS by CL macrophage (CL MAC)/TNF-α by progesterone (P4), and to examine the hypothesis that P4 acting via the genomic P4 receptor (PGR) inhibits CL MAC TNF-α and thus plays a key role in regulating LS during the pig estrous cycle. In experiment 1, the effects of LCs on CL MAC cytokine/TNF-α mRNA expression in co-culture were examined (MID cycle; ~d 7–12; no LS); results showed that LC was inhibitory to cytokine/TNF-α. In experiment 2, the effects of P4 or R5020 (PGR-agonist) on CL MAC cytokine/TNF-α mRNA expression were examined (MID cycle; ~d 7–12; no LS); results showed that both P4 and R5020 dose-dependently inhibited TNF-α. In experiment 3, CL MACs were isolated from CL at MID (~d 7–12; no LS) and LATE (~d 13–18; + LS) cycle, and TNF-α/PGR mRNA measured. Results indicated that while TNF-α mRNA was 4.2-fold greater in CL MACs from LATE vs MID cycle, PGR mRNA was 4.5-fold greater in CL MACs from MID vs LATE cycle. These data support our hypothesis and suggest that progesterone, acting via PGR, plays a critical physiological role in the control of TNF-α production by CL MACs and LS during the pig estrous cycle.}, journal={Domestic Animal Endocrinology}, publisher={Elsevier BV}, author={Gadsby, J.E. and Frandsen, S. and Chang, J. and Celestino, B. and Tucker, E. and Poole, D.H.}, year={2019}, month={Dec}, pages={106426} } @inbook{baeumer_bailey_gadsby_2018, place={New Jersey, USA}, edition={10th}, title={Hormones Affecting Reproduction}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Baeumer, W. and Bailey, C.S. and Gadsby, J.E.}, editor={Riviere, J. and Papich, M.Editors}, year={2018}, pages={674–690} } @article{chang_frandsen_d’annibale-tolhurst_palumbo_gadsby_2018, title={Prostaglandin (PTG) E and F receptors in the porcine corpus luteum; effect of tumor necrosis factor-α}, volume={195}, ISSN={0378-4320}, url={http://dx.doi.org/10.1016/J.ANIREPROSCI.2018.05.017}, DOI={10.1016/J.ANIREPROSCI.2018.05.017}, abstractNote={The porcine corpus luteum (CL) is NOT sensitive to the luteolytic effects of PGF-2α until days 12-13 of cycle. The control of "luteolytic sensitivity" (LS) of the pig CL to PGF-2α is unknown, but it is temporally associated with macrophage infiltration into the CL. Since macrophages are the predominant source of TNF-α in the porcine CL, in other studies we examined the effects of TNF-α on porcine luteal cells in culture and showed that TNF-α induces LS in vitro. In Experiment 1 of this study possible mechanisms involved in the control of LS were examined, and involved measurement of the protein levels of PTGER2/EP-2, and PTGER3/EP-3 in porcine CL collected before (days 7-10), versus after (day 13), the onset of the LS. In Experiment 2, an examination of potential mechanisms involved in the control of LS by TNF-α, was carried out in which the effects of TNF-α on mRNA and protein expression of EP-2, EP-3 and FP in cultured luteal cells, were examined. The results of Experiment 1 showed that PTGER-3/EP-3 (but not PTGER-2/EP-2) levels decreased in porcine CLs after (day 13) compared to before (day 7-10) LS. In Experiment 2, the data obtained showed that TNF-α decreased PTGER-3/EP-3 and increased PTGFR/FP protein (in EARLY stage CL). In conclusion, these studies suggest a role for PTGER-3/EP-3 in the acquisition of LS, and support the hypothesis that TNF-α from CL macrophages plays a critical role in the control of LS in the porcine CL, by increasing PTGFR/FP, and decreasing PTGER-3/EP-3 protein.}, journal={Animal Reproduction Science}, publisher={Elsevier BV}, author={Chang, J. and Frandsen, S. and D’Annibale-Tolhurst, M. and Palumbo, N. and Gadsby, J.}, year={2018}, month={Aug}, pages={139–148} } @article{chang_frandsen_gadsby_2017, title={Prostaglandin synthesis by the porcine corpus luteum: effect of tumor necrosis factor-alpha}, volume={58}, ISSN={["1879-0054"]}, DOI={10.1016/j.domaniend.2016.07.001}, abstractNote={The porcine corpus luteum (CL) displays delayed sensitivity to PGF-2α (luteolytic sensitivity, [LS]) until days 12 to 13 of cycle. The control of LS is unknown, but it is temporally associated with macrophage (which secrete tumor necrosis factor-α; TNF-α) infiltration into the CL. Other studies showed that TNF-α induces LS in vitro and that prostaglandins (PGs) may be involved in this mechanism. In experiment 1, PGF-2α and PGE secretion by luteal cells (LCs) was measured on days 4 to 14 of the estrous cycle, and the expression of PTGFS/AKR1B1 and PTGES/mPGES-1, determined by Western blot, before (day 7) vs after (day 13) the onset of LS. Results showed that the PGF-2α:PGE ratio increased significantly (P < 0.05) from day 4 to 13-14, and PTGFS/AKR1B1 and PTGES/mPGES-1 were significantly increased (P < 0.05) on day 13 (vs day 7). In experiment 2, LCs were collected from porcine CL at early (∼days 4-6) or mid (∼days 7-12) stages of the estrous cycle and cultured with 0, 0.1, 1, or 10 ng/mL TNF-α. Results showed that TNF-α significantly increased (P < 0.05) messenger RNA (mRNA) expression of cyclooxygenase (COX)-2 and mPGES-1 but not AKR1B1. TNF-α had no significant effects on AKR1B1 or mPGES protein abundance. TNF-α significantly increased (P < 0.05) PGE-2 but had no effect on PGF-2α secretion or on the PGF-2α:PGE2 ratio. In conclusion, although TNF-α increased COX2 and mPGES-1 mRNA, and PGE-2 secretion in vitro, it did not increase the PGF-2α:PGE2 ratio. Studies are currently directed toward exploring other pathways (eg, FP receptor signaling) by which TNF-α induces LS in the porcine CL.}, journal={DOMESTIC ANIMAL ENDOCRINOLOGY}, author={Chang, J. and Frandsen, S. and Gadsby, J. E.}, year={2017}, month={Jan}, pages={53–62} } @article{gadsby_nipper_faircloth_m. d'annibale-tolhurst_chang_farin_sheldon_poole_2017, title={Toll-like receptor and related cytokine mRNA expression in bovine corpora lutea during the oestrous cycle and pregnancy}, volume={52}, ISSN={["1439-0531"]}, DOI={10.1111/rda.12940}, abstractNote={Contents}, number={3}, journal={REPRODUCTION IN DOMESTIC ANIMALS}, author={Gadsby, J. E. and Nipper, A. M. Tyson and Faircloth, H. A. and M. D'Annibale-Tolhurst and Chang, J. and Farin, P. W. and Sheldon, I. M. and Poole, D. H.}, year={2017}, month={Jun}, pages={495–504} } @article{zorrilla_d'annibale_swing_gadsby_2013, title={Expression of Genes Associated with Apoptosis in the Porcine Corpus Luteum During the Oestrous Cycle}, volume={48}, ISSN={["1439-0531"]}, DOI={10.1111/rda.12156}, abstractNote={Contents}, number={5}, journal={REPRODUCTION IN DOMESTIC ANIMALS}, author={Zorrilla, L. M. and D'Annibale, M. A. and Swing, S. E. and Gadsby, J. E.}, year={2013}, month={Oct}, pages={755–761} } @article{zorrilla_sriperumbudur_gadsby_2010, title={Endothelin-1, endothelin converting enzyme-1 and endothelin receptors in the porcine corpus luteum}, volume={38}, ISSN={["0739-7240"]}, DOI={10.1016/j.domaniend.2009.08.006}, abstractNote={Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F-2alpha (PGF-2alpha) (ie, luteolytic sensitivity [LS]) until about day 12-13 of the estrous cycle. Although little is known of the control of LS in any species, endothelin-1 (EDN1) is believed to play a role in LS control in ruminants. Therefore, we measured mRNA and protein expression and examined the cellular localization of EDN1 precursor (pre-pro EDN1, or ppEDN1), EDN-converting enzyme-1 (ECE1), and EDN receptors (A, EDNRA and B, EDNRB) in porcine CLs collected on days 4, 7, 10, 13, and 15 of the estrous cycle to look for differences between CLs displaying (days 13-15) versus those lacking (days 4-10) LS. Abundance of ppEDN1 mRNA was greatest (and significant vs all other days) on day 7 of the cycle, whereas EDN1 protein expression did not vary during the cycle and was localized exclusively to endothelial cells (EC). Abundance of ECE1 mRNA was also greatest on day 7 (vs all other days), but ECE1 protein was significantly elevated on day 10 (vs day 4) and was immunolocalized to ECs and large luteal cells (LLC). Abundance of EDNRA mRNA was also maximal on day 7 (vs all other days) of the cycle, whereas EDNRA protein expression was not significantly changed during the cycle and was observed in LLCs, ECs, and small luteal cells (SLC). On day 13, EDNRB mRNA was significantly decreased (versus day 7). Expression of EDNRB protein was decreased on day 10 (versus all other days), and on days 13-15 (vs day 4), and was primarily localized to ECs. In conclusion, the observed elevation in ECE1 protein concentrations on day 10 and the presence of EDNRA on LLC suggests a possible role for EDN1 (resulting from the actions of ECE1) acting via EDNRA in the control of LS in the pig.}, number={2}, journal={DOMESTIC ANIMAL ENDOCRINOLOGY}, author={Zorrilla, L. M. and Sriperumbudur, R. and Gadsby, J. E.}, year={2010}, month={Feb}, pages={75–85} } @article{sriperumbudur_zorrilla_gadsby_2010, title={Transforming growth factor-beta (TGF beta) and its signaling components in peni-ovulatory pig follicles}, volume={120}, ISSN={["1873-2232"]}, DOI={10.1016/j.anireprosci.2010.03.003}, abstractNote={The present studies investigated the hypothesis that TGFβ plays a role in mediating LH/hCG-induced maturation, ovulation and/or luteinization of follicles in the pig. In Experiment 1, the temporal and spatial gene expression patterns of TGFβ signaling components were examined in pig follicles which had been induced to ovulate and luteinize in vivo by hCG treatment, or by the LH-surge. Pre-pubertal pigs were injected with PG-600 followed by hCG, and ovaries were collected surgically at 0, 1, 12, 24 and 48 h post-hCG. Post-ovulatory follicles were also collected from cycling gilts on Day 4 (D4) of the estrous cycle. Pre- and post-ovulatory follicles were used for the measurement of mRNA (PCR) and protein (Western blots) abundance and for protein localization by immunohistochemistry (IHC). Steady state amounts of mRNA for TGFβ3 and TGFβR2 were increased (P < 0.05, as compared to 0 h) at 12 h and on D4, respectively, while TGFβ2 protein showed a tendency to increase on D4. TGFβ signaling components did not change significantly. By IHC, the localization of TGFβ components was as follows: pre-ovulatory follicles; TGFβ1 – granulosa cells (GC), TGFβ2 – theca cells (TC), TGFβR1 and 2 – GC and TC: post-ovulatory follicles; TGFβ1 and 2 and TGFβR1 and 2 – luteinizing TC and GC. In Experiment 2, TGFβ1 (1–100 ng/ml) alone had no significant effect on progesterone (P4) secretion by pig GC in culture. Furthermore, while LH + IGF-1 (positive control) stimulated P4 ∼10-fold, TGFβ at 10 and 100 ng/ml added in combination with LH + IGF-1, had no effect on P4 accumulation. In conclusion, data from the present study on temporal and spatial patterns of expression of the TGFβ-system suggest that TGFβ may play a role in the overall process of luteinization, but it appears not to influence steroidogenesis in luteinizing pig follicles.}, number={1-4}, journal={ANIMAL REPRODUCTION SCIENCE}, author={Sriperumbudur, Rajagopal and Zorrilla, Leah and Gadsby, John E.}, year={2010}, month={Jul}, pages={84–94} } @inbook{reddy_gadsby_2009, place={New York, USA}, edition={9th Edition}, title={Hormones Affecting Reproduction}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Blackwell}, author={Reddy, D.S. and Gadsby, J.E.}, editor={Riviere, J. and Papich, M.Editors}, year={2009}, pages={717–733} } @article{sheldon_price_cronin_gilbert_gadsby_2009, title={Mechanisms of Infertility Associated with Clinical and Subclinical Endometritis in High Producing Dairy Cattle}, volume={44}, ISSN={["1439-0531"]}, DOI={10.1111/j.1439-0531.2009.01465.x}, abstractNote={Contents}, journal={REPRODUCTION IN DOMESTIC ANIMALS}, author={Sheldon, I. M. and Price, S. B. and Cronin, J. and Gilbert, R. O. and Gadsby, J. E.}, year={2009}, month={Sep}, pages={1–9} } @article{zorrilla_irvin_gadsby_2009, title={Protein kinase C isoforms in the porcine corpus luteum: Temporal and spatial expression patterns}, volume={36}, ISSN={["1879-0054"]}, DOI={10.1016/j.domaniend.2008.10.008}, abstractNote={Porcine corpora lutea (CL) fail to show a luteolytic response to prostaglandin-F-2α (PGF-2α) (ie, luteolytic sensitivity, or LS) until ∼day 13 of the estrous cycle. In view of the importance of protein kinase C (PRKC) in PGF-2α signal transduction, it was hypothesized that limiting levels of 1 or more PRKC isoforms may explain the lack of LS before day 13. This hypothesis was tested by examining expression of mRNA and protein, and the cellular localization patterns of the 11 PRKC isoforms throughout the porcine estrous cycle, to determine whether PRKC expression correlates with and thus may be associated with the control of the acquisition of LS in the pig. The expression patterns show that for most PRKC isoforms (ie, PRKC alpha, beta 1, beta 2, delta, epsilon, theta, iota, and zeta), mRNA was maximally expressed on day 7 or day 10 (protein kinase D1 only) of the cycle, whereas PRKCs gamma, eta, and lambda were unchanged. At the protein level, only PRKC epsilon (PRKCE) significantly changed during the estrous cycle and was elevated on day 13 (versus days 4, 7, and 15; P < 0.05). By immunofluoresence, most PRKC isoforms, including PRKCE, were localized to steroidogenic large luteal cells (LLC) and small (nonendothelial cell) luteal cell subtypes (SLC). In conclusion, since the increase in PRKCE protein expression (day 13) occurred coincidentally with the onset of LS (≥day 12), these results support a potential role for PRKCE in control of the acquisition of LS in the pig.}, number={4}, journal={DOMESTIC ANIMAL ENDOCRINOLOGY}, author={Zorrilla, L. M. and Irvin, M. S. and Gadsby, J. E.}, year={2009}, month={May}, pages={173–185} } @article{whang_vendeix_gracz_gadsby_tonelli_2008, title={NMR studies of the inclusion complex of cloprostenol sodium salt with beta-cyclodextrin in aqueous solution}, volume={25}, ISSN={["1573-904X"]}, DOI={10.1007/s11095-007-9493-z}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} Cloprostenol sodium salt (referred as cloprostenol) may be used for the synchronization of estrous cycles in farm animal species. Cyclodextrins (CDs) have potential as drug delivery systems through the formation of inclusion complexes between CDs and drugs. This is the first study of the inclusion complex of cloprostenol with beta-cyclodextrin (beta-CD) in aqueous solution using NMR and 3D molecular dynamics simulations. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} 1D proton NMR spectra of beta-CD, a complex of cloprostenol with beta-CD, and cloprostenol in D(2)O were assigned and confirmed. The cross relaxation interactions from ROESY were used as constraints for 3D molecular modeling studies. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} In the 2D ROESY of the complex, cross-peaks were observed between the aromatic protons of cloprostenol and protons of the beta-CD as well as between aliphatic protons and protons of the beta-CD. The stoichiometry of the complex was found that beta-CD forms a 1:1 inclusion complex with cloprostenol. The association constant K was 968 +/- 120 M(-1) at 298 K. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Aromatic side and/or aliphatic side chains of the cloprostenol is included in the beta-CD while aliphatic side and/or aromatic side chains wraps around beta-CD, respectively. The molecular modeling also confirms that beta-CD forms a 1:1 inclusion complex with cloprostenol.}, number={5}, journal={PHARMACEUTICAL RESEARCH}, author={Whang, Hyun Suk and Vendeix, Franck A. P. and Gracz, Hanna S. and Gadsby, John and Tonelli, Alan}, year={2008}, month={May}, pages={1142–1149} } @inbook{gadsby_rose_sriperumbudur_ge_2006, place={Nottingham, U.K}, title={The role of intra-luteal factors in the control of the porcine corpus luteum}, booktitle={Control of Pig Reproduction VII, Reproduction Supplement 62}, publisher={Nottingham University Press}, author={Gadsby, J. and Rose, L. and Sriperumbudur, R. and Ge, Z.}, editor={Ashworth, Eds C.J. and Kraeling, R.R.Editors}, year={2006}, pages={69–83} } @article{boonyaprakob_gadsby_hedgpeth_routh_almond_2005, title={Expression and localization of hypoxia inducible factor-1 alpha mRNA in the porcine ovary}, volume={69}, number={3}, journal={Canadian Journal of Veterinary Research}, author={Boonyaprakob, U. and Gadsby, J. E. and Hedgpeth, V. and Routh, P. A. and Almond, G. W.}, year={2005}, pages={215–222} } @article{boonyaprakob_gadsby_hedgpeth_routh_almond_2003, title={Cloning of pig prostaglandin F-2 alpha(FP) receptor cDNA and expression of its mRNA in the corpora lutea}, volume={125}, DOI={10.1530/rep.0.1250053}, abstractNote={Changes in the expression and localization of luteal mRNA for PGF(2alpha) (FP) receptors may be critical in determining the luteolytic action of PGF(2alpha) in pig corpora lutea. In this study, a full-length FP receptor (FPr) cDNA was isolated and cloned from pig corpora lutea. This isolate (GenBank accession no. U91520) contains an open reading frame of 1086 bases coding for a protein of 362 amino acids with seven potential transmembrane domains. The predicted amino acid sequence of this isolate was 83% identical to the FPr amino acid sequence of other species including sheep, cattle and humans. Northern blot analysis showed the presence of an FPr message of about 5 kb in mRNA from pig corpora lutea. Relatively weak FPr mRNA expression was detected on day 4 and day 7 of the oestrous cycle. The expression was greater (P < 0.05) on days 10, 13 and 15 than on days 4 and 7. In situ hybridization analysis revealed that mRNA for FPr was expressed predominantly in the steroidogenic large luteal subtype of cell, although there was some expression in small luteal cells, with histological appearance of steroidogenic small cells. Localization of hybridization signals of FPr was observed in luteal tissue at all stages examined. These data demonstrate that FPr is expressed in pig corpora lutea throughout the oestrous cycle and that upregulation of the FPr mRNA occurs when the corpora lutea becomes sensitive to PGF(2alpha). Direct luteal targets of PGF(2alpha) appear to be primarily large steroidogenic cells in this species.}, number={1}, journal={Reproduction (Cambridge, England)}, author={Boonyaprakob, U. and Gadsby, John and Hedgpeth, V. and Routh, P. and Almond, Glen}, year={2003}, pages={53–64} } @article{boonyaprakob_gadsby_hedgpeth_routh_almond_2003, title={Expression and localization of vascular endothelial growth factor and its receptors in pig corpora lutea during the oestrous cycle}, volume={126}, DOI={10.1530/rep.0.1260393}, abstractNote={Expression and localization of mRNAs for vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt) and VEGF receptor 2 (KDR) (VEGFR-1 and VEGFR-2, respectively) were investigated in pig corpora lutea. Northern blot analysis of total RNA indicated hybridization of pig VEGF, VEGFR-1 and VEGFR-2 cDNA probes to mRNA transcripts of approximately 3.9, 7.0 and 5.0 kb, respectively. The expression of mRNAs for VEGF and its receptors during the luteal phase (days 4, 7, 10, 13 and 15 after the onset of oestrus) were assessed by northern blot analysis, and hybridization signals were normalized to expression of pig 18S rRNA. Relative hybridization signals of expression of VEGF mRNA appeared to be constant; however, expression of VEGFR-1 mRNA was low on day 4, increased on day 7, and was higher on days 10, 13 and 15 (P<0.05, compared with day 4). In contrast, no changes in expression of mRNA for VEGFR-2 were evident on days 4-13, but a decrease was detected (P<0.05) at day 15. In situ hybridization revealed that VEGF mRNA was localized predominantly in large luteal cells, whereas both VEGFR-1 and VEGFR-2 were localized to small cells. These data indicate that the VEGF system may be involved in the regulation of luteal vasculature throughout the lifespan of the corpus luteum. Although the expression of VEGF mRNA was unchanged during the luteal phase, variations in the expression of VEGFR-1 and VEGFR-2 mRNAs indicate that differential regulation of expression of the VEGF receptors may play a role in the control of VEGF-mediated vascular growth at different phases of development and maturation of the pig corpus luteum.}, number={3}, journal={Reproduction (Cambridge, England)}, author={Boonyaprakob, U. and Gadsby, John and Hedgpeth, V. and Routh, P. and Almond, Glen}, year={2003}, pages={393–405} } @article{ge_miller_nicholson_hedgpeth_gadsby_2003, title={Insulin-like growth factor (IGF)-I and IGF binding proteins-2,-3,-4,-5 in porcine corpora lutea during the estrous cycle; evidence for inhibitory actions of IGFBP-3}, volume={25}, ISSN={["1879-0054"]}, DOI={10.1016/S0739-7240(03)00060-2}, abstractNote={In this study we measured protein concentrations of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) 2-5 in porcine corpora lutea (CLs) throughout the estrous cycle (Experiment 1), and examined the effects of IGFBP-3 and IGFBP-3 antibody (AB) on luteal progesterone (P4) secretion in vitro (Experiment 2). For Experiment 1, (CLs) and serum were collected on days (D) 4, 7, 10, 13, 15 and 16 of the estrous cycle (n = 5 animals per day). IGF-I was extracted from CLs and sera, and measured by radioimmunoassay (RIA). IGFBPs were measured in CLs by ligand blots. For Experiment 2, CLs (from Experiment 1) were enzyme dissociated and luteal cells cultured (24 h) in Medium 199 (M199) containing (0-500 ng/ml) IGFBP-3 (+/-IGF-I; 100 ng/ml), or (0-10 microg/ml) IGFBP-3 AB. P4 in media was measured by RIA. In Experiment 1, luteal IGF-I concentrations (ng/g tissue) were maximal on day 4 and gradually decreased thereafter. Serum IGF-I concentrations (ng/ml) were highest on days 4 and 7, compared with days 10-15. Peak levels of luteal IGFBP-3 were also seen on days 4 and 7 of the cycle. Luteal IGFBP-2 concentrations showed a tendency to increase on day 16 (P < 0.05 versus day 10), but no significant changes in IGFBP-4 or -5 were seen. In Experiment 2, IGFBP-3 (w IGF) inhibited the steroidogenic actions of IGF-I, but had no significant actions alone (IGFBP-3 w/o IGF). Finally, IGFBP-3 AB stimulated P4 secretion on days 4 and 7, but not on days 10-16. We conclude that IGFBP-3 inhibits IGF-I actions in the porcine CL.}, number={2}, journal={DOMESTIC ANIMAL ENDOCRINOLOGY}, author={Ge, ZP and Miller, E and Nicholson, W and Hedgpeth, V and Gadsby, J}, year={2003}, month={Aug}, pages={183–197} } @article{miller_ge_hedgpeth_gadsby_2003, title={Steroidogenic responses of pig corpora lutea to insulin-like growth factor I (IGF-I) throughout the oestrous cycle}, volume={125}, ISSN={["1470-1626"]}, DOI={10.1530/rep.0.1250241}, abstractNote={This study was designed to investigate the roles of insulin-like growth factor I (IGF-I), IGF-type I receptor (IGF-IR) and IGF-binding proteins (IGFBPs) in regulating progesterone secretion by pig corpora lutea during the oestrous cycle, and the signal transduction pathways involved in mediating the steroidogenic actions of IGF-I. Corpora lutea were collected on days 4, 7, 10, 13 and 15 or 16 of the oestrous cycle, enzyme dissociated and the luteal cells were cultured for 24 h in Medium 199 with IGF-I (0-100 ng ml(-1)), long R(3)-IGF-I (0-100 ng ml(-1)), anti-IGF-I (Sm 1.2B; 0-10 microg ml(-1)), anti-IGF-IR (alphaIR3; 0-2 microg ml(-1)), or IGF-I signal transduction pathway inhibitors (phosphatidylinositol (PI)-3-kinase: 100 nmol Wortmannin l(-1) and 10 micromol LY 294002 l(-1); MAP kinase: 50 micromol PD 98059 l(-1)) to investigate their effects on IGF-I (100 ng ml(-1)) stimulated progesterone secretion. Pig luteal cells displayed dose-dependent responses to IGF-I and long R(3)-IGF-I on days 4 and 7 of the oestrous cycle, but not on days 10-16. There was no difference in the ED(50) or V(max) (maximal response) values between IGF-I and long R(3)-IGF-I. Neither anti-IGF-I nor anti-IGF-IR had significant effects on progesterone secretion, at any dose or day. Wortmannin and LY 294002 blocked IGF-I stimulated progesterone secretion, but PD 98059 was without effect. Finally, IGF-I (6 microg) infused into the ovary on day 7 in vivo significantly increased progesterone secretion within 45 min of infusion. The conclusions of this study are: (1) IGF-I has steroidogenic actions only on 'young' (days 4-7) pig corpora lutea; (2) endogenous IGF-I and IGFBP are insufficient to modulate progesterone secretion in vitro; and (3) the steroidogenic actions of IGF-I are mediated via PI-3-kinase.}, number={2}, journal={REPRODUCTION}, author={Miller, EA and Ge, Z and Hedgpeth, V and Gadsby, JE}, year={2003}, month={Feb}, pages={241–249} } @article{ge_nicholson_plotner_farin_gadsby_2000, title={Insulin-like growth factor I receptor Mrna and protein expression in pig corpora lutea}, volume={120}, DOI={10.1530/jrf.0.1200109}, abstractNote={Insulin-like growth factor I (IGF-I) is believed to play a luteotrophic role in the pig corpus luteum during the oestrous cycle. Since the actions of IGF-I in target tissues are mediated by the type I IGF receptor, the concentrations of IGF-I receptor mRNA and protein were examined in pig corpora lutea at different stages of the oestrous cycle. Corpora lutea were collected from normally cyclic gilts on days 4, 7, 10, 13, 15 and 16 of the oestrous cycle (n = 4 animals per day). Corpora lutea on days 7, 10 and 13 were dissociated with collagenase, and large and small luteal cell sub-populations were separated by elutriation. Northern and slot blots were used to examine mRNA, and western blots were used to measure the concentrations of IGF-I receptor protein in the pig corpus luteum. On northern blots, luteal IGF-I receptor mRNA was present as a single 11 kb transcript. The slot blots showed that the steady state expression of IGF-I receptor mRNA increased significantly (P < 0.05) from its lowest value on day 4, to reach a maximum on days 13-16. IGF-I receptor mRNA was also expressed to a greater extent in large compared with small luteal cells (P < 0.05). On western blots, IGF-I receptor appeared as a 95 kDa protein band (beta-subunit) and IGF-I receptor protein concentrations were significantly higher (P < 0.05) on days 4-10 than on days 13-16. Finally, large luteal cells appeared to contain more IGF-I receptor protein than the small luteal cells. In conclusion, since IGF-I receptor was detected in the pig corpus luteum, it is a likely target tissue for IGF-I, especially during the early luteal phase. Furthermore, IGF-I receptor was localized primarily on large luteal cells, thus it is hypothesized that IGF-I may play a paracrine role in the pig corpus luteum.}, number={1}, journal={Journal of Reproduction & Fertility}, author={Ge, Z. and Nicholson, W. E. and Plotner, D. M. and Farin, C. E. and Gadsby, John}, year={2000}, pages={109–114} } @article{wandji_gadsby_barber_hammond_2000, title={Messenger ribonucleic acids for MAC25 and connective tissue growth factor (CTGF) are inversely regulated during folliculogenesis and early luteogenesis}, volume={141}, ISSN={["1945-7170"]}, DOI={10.1210/en.141.7.2648}, abstractNote={Cell proliferation, terminal differentiation, and angiogenesis occur during cycles of follicular and luteal development. In other paradigms, mac25, a potent tumor inhibitor is strongly induced in senescent epithelial cells, whereas CTGF stimulates angiogenesis and wound healing. Using in situ hybridization and immunohistochemistry, we have examined the possibilities that mac25 is inhibited, whereas CTGF is induced during active periods of follicular development and luteogenesis. Ovaries were collected during the follicular and early luteal phases from prostaglandin F2α-treated mature pigs and from slaughterhouse sows. CTGF transcripts were induced during the late preantral stage in granulosa and theca cells concomitantly with the appearance of endothelial cells in the theca. CTGF mRNA expression increased in granulosa cells to a maximum (P < 0.01) in mid-antral follicles but was down regulated (P < 0.01) in preovulatory follicles. In contrast, granulosa cell mac25 mRNA expression was undetectable between the preantral and mid-antral stage but was strongly induced in terminally differentiated granulosa cells of preovulatory follicles. CTGF mRNA and peptide were also detected in the theca externa/interstitium and in vascular endothelial cells of ovarian blood vessels, whereas mac25 transcripts, which were also abundant in ovarian blood vessels increased in the theca interna with follicular development. Transcripts of cyclin D1, a marker of cell proliferation, appeared during the early antral stage and were moderate in granulosa cells but abundant in capillary endothelial cells in the theca interna, underneath the basement membrane. Following ovulation, CTGF and cyclin D1 mRNAs were associated with the migration of endothelial cells into the CL. Subsequently, there was a marked up-regulation of CTGF mRNA expression in granulosa luteins concomitantly with an increase in endothelial cell proliferation within the CL. We hypothesize that CTGF may promote ovarian cell growth and blood vessel formation during follicular and luteal development whereas mac25, a tumor inhibitor, may promote terminal differentiation of granulosa cells in preovulatory follicles.}, number={7}, journal={ENDOCRINOLOGY}, author={Wandji, SA and Gadsby, JE and Barber, JA and Hammond, JM}, year={2000}, month={Jul}, pages={2648–2657} } @article{wandji_gadsby_simmen_barber_hammond_2000, title={Porcine ovarian cells express messenger ribonucleic acids for the acid-labile subunit and insulin-like growth factor binding protein-3 during follicular and luteal phases of the estrous cycle}, volume={141}, ISSN={["1945-7170"]}, DOI={10.1210/en.141.7.2638}, abstractNote={It has recently been shown that, in follicular fluid, as in the circulation, insulin-like growth factors (IGFs)-I and -II exist in a ternary complex with IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). The current study was designed to determine whether ovarian follicular and luteal cells could synthesize IGFBP-3 and ALS. Ovaries were collected, during the follicular and early luteal phases, from mature pigs whose cycles were synchronized with PGF2α. We studied IGFBP-3 and ALS messenger RNA (mRNA) by in situ hybridization. These transcripts were colocalized with aromatase mRNA, a marker of healthy granulosa cells. IGFBP-3 mRNA was equally expressed in granulosa cells of all growing follicles. In contrast, granulosa cell ALS mRNA levels were higher (P < 0.05) in preantral and small antral follicles than in large antral follicles. In thecal cells, expression of mRNA for IGFBP-3, ALS and cyclin D1 (a marker of cell proliferation) was restricted to healthy (aromatase-expressing) follicles. In those follicles, thecal expression of IGFBP-3 mRNA was low or absent in preantral follicles but increased (P < 0.05) in antral follicles. Thecal cell ALS transcripts peaked in small antral follicles (P < 0.05) and then declined. In granulosa cells of atretic follicles, transcripts for aromatase were greatly reduced, whereas IGFBP-3 mRNA levels remained high. In contrast, ALS transcript levels were greatly reduced in both granulosa (P < 0.05) and thecal cells (P< 0.001) of atretic follicles. After ovulation, IGFBP-3 mRNA was moderately expressed in granulosa luteins but strongly detected in a few theca-derived cells and in vascular endothelial cells. This study demonstrates that follicular fluid IGFBP-3 and ALS, like the IGFs, originate (at least in part) from the ovary. The ability of follicular cells to synthesize, assemble, and store all components of the ternary complex may be critical in determining the bioavailability of follicular IGF-I and -II.}, number={7}, journal={ENDOCRINOLOGY}, author={Wandji, SA and Gadsby, JE and Simmen, FA and Barber, JA and Hammond, JM}, year={2000}, month={Jul}, pages={2638–2647} } @article{nicholson_ge_plotner_farin_gadsby_1999, title={Insulin-like growth factor (IGF)-I, ICF-I receptor, and IGF binding protein-3 messenger ribonucleic acids and protein in corpora lutea from prostaglandin F-2 alpha-treated gilts}, volume={61}, ISSN={["1529-7268"]}, DOI={10.1095/biolreprod61.6.1527}, abstractNote={Insulin-like growth factor-I (IGF-I) is produced within the porcine corpus luteum (CL) and is thought to play an autocrine/paracrine role in CL development/function during the early luteal phase. This study examines the hypotheses that the luteolytic actions of prostaglandin F(2alpha) (PGF(2alpha)) during the early luteal phase may involve either a decrease in IGF-I or IGF receptor (IGF-IR), or an increase in IGF binding protein (IGFBP)-3, expression, any of which could interfere with the luteotropic actions of IGF-I in this tissue. Cycling gilts were treated twice daily with PGF(2alpha) (or saline) on Days 5-9 of the cycle to induce premature luteolysis. CL were collected on Days 6-9, and RNA, protein, or progesterone was extracted. By slot blot analysis, steady-state levels of IGF-I and IGFBP-3 mRNA were not different in PGF(2alpha)-treated vs. control animals; however, IGF-IR mRNA was increased in treated animals on Day 9. No changes in IGF-I content (ng/CL measured by RIA) were observed with respect to treatment. According to ligand blot analysis, the levels of IGFBP-3 increased on Day 6 and decreased on Days 8-9, while IGFBP-2 was higher on Days 6-7 and decreased on Day 9 in treated animals. IGF-IR levels, determined from Western blots, were higher on Day 7 (P < 0.05) and lower on Day 9 in PGF(2alpha)-treated animals vs. control animals (P < 0.05). In conclusion, PGF(2alpha)-induced premature luteolysis was associated with an increase in steady-state levels of IGF-IR mRNA, but it did not appear to be linked to changes in mRNA levels for IGF-I or IGFBP-3. However, since IGFBP-2 and -3 protein levels increased early in the treatment period (Days 6-7), it is possible that they may mediate the luteolytic actions of PGF(2alpha) by sequestering IGF-I and preventing its interaction with the IGF-IR.}, number={6}, journal={BIOLOGY OF REPRODUCTION}, author={Nicholson, WCE and Ge, ZP and Plotner, DM and Farin, CE and Gadsby, JE}, year={1999}, month={Dec}, pages={1527–1534} } @article{wandji_gadsby_barber_hammond_1999, title={Ovarian expression of Mac25/IGFBP-7 and connective tissue growth factor/IGFBP-8 during porcine follicular phase.}, volume={60}, number={1999}, journal={Biology of Reproduction}, author={Wandji, S. A. and Gadsby, J. E. and Barber, J. and Hammond, J. M.}, year={1999}, pages={173} } @article{gadsby_lovdal_samaras_barber_hammond_1996, title={Expression of the Messenger Ribonucleic Acids for Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Proteins in Porcine Corpora Lutea}, volume={54}, ISSN={0006-3363 1529-7268}, url={http://dx.doi.org/10.1095/biolreprod54.2.339}, DOI={10.1095/biolreprod54.2.339}, abstractNote={In the pig, the corpus luteum (CL) can develop and function autonomous of pituitary gonadotropins for approximately 12 days. We hypothesized that the insulin-like growth factor (IGF) system may play an autocrine/paracrine luteotrophic role(s) during this period. In this study, we monitored the expression (i.e., steady-state levels of mRNAs) of IGF-I and IGF binding proteins (IGFBP)-2, -3, -4, -5, and -6 mRNAs in whole CL and in small and large luteal cells on Days 4-16 of the estrous cycle. CL were dissociated with collagenase, and large and small luteal cells were isolated by centrifugal elutriation. Whole CL and luteal cells were extracted to isolate total or poly(A)+ RNA, which was subjected to Northern and/or dot-blot analyses using [32P]-labeled cDNA probes for IGF-I and IGFBP-2, -3, -4, -5, and -6. Northern blots showed readily detectable transcripts for IGF-I (6.7 and 0.9 kb), IGFBP-2 (1.8 kb), IGFBP-3 (2.8 kb), IGFBP-4 (2.6 kb), and IGFBP-5 (6.0 kb), but not for IGFBP-6. IGFBP-3 and -5 transcripts were observed mainly in small luteal cells, while IGFBP-2 and -4 were seen in both cell types. Dot-blot analyses for IGF-I and IGFBP-3 mRNAs were performed on total RNA from small and large luteal cells; blots were counter-probed with 3-phosphoglyceraldehyde dehydrogenase (p-GAD) cDNA to assess RNA quantity and quality. IGF-I mRNA (ratio IGF-I:p-GAD mRNA) expression was approximately 2-fold greater in small than in large luteal cells on Days 4-10. However, steady-state levels of IGF-I mRNA in small, but not large, luteal cells decreased significantly on Days 12-16 (vs. Days 4-10). IGFBP-3 mRNA expression was significantly greater (approximately 3-fold) in small than in large luteal cells but did not vary significantly between Days 4-10 and 12-16 for either cell type. We conclude that porcine CL express mRNAs for IGF-I and IGFBP-2, -3, -4, and -5, and that while small luteal cells are the major sources of IGF-I and IGFBP-3 and -5, IGFBP-2 and -4 appear to be expressed to approximately the same extent in small and large luteal cells. These results further suggest that the IGF-I/IGF system may have autocrine/paracrine regulatory actions in CL development/function in the pig.}, number={2}, journal={Biology of Reproduction}, publisher={Oxford University Press (OUP)}, author={Gadsby, John E. and Lovdal, Jamie A. and Samaras, Susan and Barber, Judy S. and Hammond, James M.}, year={1996}, month={Feb}, pages={339–346} } @inproceedings{gadsby_grafinger_almond_1996, place={Bologna, Italy}, title={Short-cycling of gilts with prostaglandin analogs}, booktitle={Proceedings of the 14th International Pig Veterinary Society Congress}, publisher={Scientific Committee of the 14th IPVS Congress}, author={Gadsby, J.E. and Grafinger, M. and Almond, G.}, editor={Monetti, P.G. and Vignola, G.Editors}, year={1996}, pages={564} } @article{estill_britt_gadsby_1995, title={Does increased PGF2α receptor concentration mediate PGF2α-induced luteolysis during early diestrus in the pig?}, volume={49}, ISSN={0090-6980}, url={http://dx.doi.org/10.1016/0090-6980(94)00010-t}, DOI={10.1016/0090-6980(94)00010-t}, abstractNote={The mechanism by which multiple injections of PGF2 alpha result in premature luteolysis in pigs is unknown. In the present study we evaluated whether PGF2 alpha receptor concentrations on large luteal cells changed when gilts were injected IM with 12.5 mg of PGF2 alpha every 12 hours from the morning of day 5 of an estrous cycle (estrus = day 0) until ovariectomy on day 6, 7, 8, or 9. Luteal PGF2 alpha receptor concentrations remained constant from day 6 through 9 in the PGF2 alpha-treated group, but increased linearly (P > 0.05) in control gilts from day 6 to 9. Receptor affinity for PGF2 alpha did not change throughout the study in either PGF2 alpha-treated or control gilts. Luteal progesterone concentrations were significantly lower in PGF2 alpha-treated gilts than in control gilts only on day 9. Histological examination of luteal tissue obtained from PGF2 alpha-treated gilts revealed definite evidence of luteolysis by day 8. We conclude that PGF2 alpha-induced premature luteolysis is not mediated by an increase in luteal PGF2 alpha receptor concentrations and, based on luteal progesterone concentrations and histological features, that the PGF2 alpha-based protocol used to shorten the estrous cycle is accompanied by premature functional and structural luteal regression.}, number={5}, journal={Prostaglandins}, publisher={Elsevier BV}, author={Estill, Charles T. and Britt, Jack H. and Gadsby, John E.}, year={1995}, month={May}, pages={255–267} } @article{richards_gadsby_almond_1994, title={Differential effects of LH and PGE2 on progesterone secretion by small and large porcine luteal cells}, volume={102}, ISSN={1470-1626 1741-7899}, url={http://dx.doi.org/10.1530/jrf.0.1020027}, DOI={10.1530/jrf.0.1020027}, abstractNote={This study examined the effects of LH and PGE2 on progesterone secretion by small and large porcine luteal cells with or without low-density lipoproteins. Corpora lutea were isolated from gilts 13-14 days after administering gonadotrophins; enzymatically dissociated and small and large cells were isolated by elutriation. Culture plates, 24-well, were then seeded with 150,000 small or 30,000 large luteal cells suspended in 1 ml M199 medium supplemented with 5 micrograms insulin ml-1, 40 ng hydrocortisone ml-1 and with or without low-density lipoproteins (50 micrograms cholesterol ml-1) or PGE2. Cells were cultured for up to 24 h in a humidified incubator at 37 degrees C under 5% CO2 in air. The low-density lipoproteins stimulated (P < 0.05) progesterone secretion by large, but not small, luteal cells. Prostaglandin E2 stimulated (P < 0.05) progesterone production by large luteal cells in a dose-dependent manner, and the stimulatory effects of PGE2 were greater (P < 0.05) in the presence than in the absence of low-density lipoproteins. Progesterone secretion by small luteal cells was not significantly affected by PGE2. Progesterone production by small luteal cells was enhanced (P < 0.05) by LH, and the stimulatory effects of LH were greater (P < 0.05) in the presence than in the absence of low-density lipoproteins. In the absence of these lipoproteins, LH had no effect on progesterone secretion by large luteal cells; however, in the presence of low-density lipoproteins, LH increased (P < 0.05) progesterone secretion by large cells, though to a lesser (P < 0.05) extent than the effect of LH on small cells. These data demonstrate that progesterone secretion by porcine luteal cells is stimulated differentially by LH and PGE2 and that small luteal cells are more responsive to LH and PGE2 acts primarily on large luteal cells.}, number={1}, journal={Reproduction}, publisher={Bioscientifica}, author={Richards, R. G. and Gadsby, J. E. and Almond, G. W.}, year={1994}, month={Sep}, pages={27–34} } @article{gadsby_earnest_1994, title={Prostaglandin F2a stimulates progesterone secretion by porcine luteal cells in vitro throughout the estrous cycle}, volume={48}, ISSN={0090-6980}, url={http://dx.doi.org/10.1016/0090-6980(94)90089-2}, DOI={10.1016/0090-6980(94)90089-2}, abstractNote={In this study we examined the stimulatory effects of PGF2 alpha on progesterone secretion by porcine luteal cells on different days of the estrous cycle, and the effects of PGF2 alpha, A23187 and PMA on progesterone secretion by isolated large and small luteal cells, in vitro. Corpora lutea were obtained from cycling pigs (days 6-16), collagenase dispersed and luteal cells incubated in medium 199 in the absence or presence of increasing doses of PGF2 alpha, A23187, and PMA. Progesterone concentrations in spent media were measured by RIA. PGF2 alpha stimulation of progesterone secretion by mixed luteal cells did not vary significantly throughout the estrous cycle. Progesterone secretion by large, but not small, luteal cells was increased (p < 0.05) in a dose-dependent fashion by PGF2 alpha. A23187 also caused a dose-dependent increase in progesterone secretion by large luteal cells but inhibited small luteal cells. Progesterone secretion by both large and small luteal cells was significantly increased by increasing doses of PMA. We conclude that the stimulatory response of luteal cells to PGF2 alpha in vitro did not correlate with PGF2 alpha receptor concentrations (not measured in this study), and we speculate that calcium/protein kinase C may be involved in mediating the stimulatory action of PGF2 alpha on luteal cell progesterone secretion.}, number={2}, journal={Prostaglandins}, publisher={Elsevier BV}, author={Gadsby, John E. and Earnest, Karla L.}, year={1994}, month={Aug}, pages={109–125} } @article{gadsby_lovdal_britt_fitz_1993, title={Prostaglandin F2α Receptor Concentrations in Corpora Lutea of Cycling, Pregnant, and Pseudopregnant Pigs}, volume={49}, ISSN={0006-3363 1529-7268}, url={http://dx.doi.org/10.1095/biolreprod49.3.604}, DOI={10.1095/biolreprod49.3.604}, abstractNote={The objective of this study was to measure and compare the concentrations of PGF 2 alpha receptors on luteal cells taken from cycling, pregnant, and pseudopregnant pigs. Corpora lutea were removed surgically from cycling, pregnant, and pseudopregnant (induced with 5 mg estradiol valerate/day i.m. beginning on Day 11) pigs on Days 12, 13, and 14 (postestrus) and were subjected to collagenase dissociation. Dissociated luteal cells (approximately 100,000 large viable cells per tube) were assayed for specific PGF 2 alpha binding by Scatchard analysis, using [3H]PGF 2 alpha and varying doses (0-5 microM) of unlabeled PGF 2 alpha. Luteal cells from all three types of pigs were shown to possess two specific PGF 2 alpha binding sites (high affinity, Kd = 9-47 nM; low affinity, Kd = 243-1359 nM). The concentrations of the high-affinity PGF 2 alpha binding site (PGF 2 alpha "receptor") on Days 12 and 13 were not significantly different (NS) between cycling (1.7 and 1.1 x 10(6) receptors per large luteal cell, respectively), pregnant (1.3 and 1.2 x 10(6)), and pseudopregnant (1.1 and 0.8 x 10(6)) pigs. However, on Day 14, luteal PGF 2 alpha receptor concentrations were significantly higher (p < 0.05) in cycling (4.2 x 10(6)) compared with pregnant (1.3 x 10(6)) and pseudopregnant (1.4 x 10(6)) pigs. We speculate that reduced luteal PGF 2 alpha receptor concentrations on Day 14 in pregnant and pseudopregnant compared with cycling pigs may lead to decreased luteal sensitivity to PGF 2 alpha in these animals, and that this mechanism may play a role in the maternal recognition of pregnancy in this species.}, number={3}, journal={Biology of Reproduction}, publisher={Oxford University Press (OUP)}, author={Gadsby, John E. and Lovdal, Jamie A. and Britt, Jack H. and Fitz, Tony A.}, year={1993}, month={Sep}, pages={604–608} } @article{estill_britt_gadsby_1993, title={Repeated Administration of Prostaglandin F2α during the Early Luteal Phase Causes Premature Luteolysis in the Pig}, volume={49}, ISSN={0006-3363 1529-7268}, url={http://dx.doi.org/10.1095/biolreprod49.1.181}, DOI={10.1095/biolreprod49.1.181}, abstractNote={Previous investigators considered pig corpora lutea refractory to the luteolytic effects of prostaglandin (PG) F2 alpha before Day 12 of the estrous cycle. This study was designed to determine whether multiple injections of PGF2 alpha would result in a sustained reduction of serum progesterone and luteolysis, leading to significant shortening of the estrous cycle and interestrous interval. On Days 5-10 of an estrous cycle, gilts (n = 4) received injections of 12.5 mg PGF2 alpha (dinoprost tromethamine) i.m. every 12 h, or vehicle (PBS; n = 4) according to the same schedule. Mean interestrous interval in PGF2 alpha-treated gilts was reduced (p < 0.001) to 13.3 +/- 0.5 days compared with 19.8 +/- 0.6 days for control gilts. Serum progesterone declined below 1 ng/ml by Day 10.5 in PGF2 alpha-treated gilts compared to Day 17.5 in control animals. Serum concentrations of estradiol-17 beta (E2) reached maximal levels in PGF2 alpha-treated gilts earlier (Day 12.5) in the cycle than in control gilts (Day 19.5). Peak E2 and LH concentrations coincided with the periestrous period, suggesting that PGF2 alpha-induced estrus is accompanied by normal follicular development and ovulation. These results demonstrate that the pig is susceptible to the luteolytic effects of PGF2 alpha before Day 12 if repeated injections are given from Day 5 through Day 10.}, number={1}, journal={Biology of Reproduction}, publisher={Oxford University Press (OUP)}, author={Estill, Charles T. and Britt, Jack H. and Gadsby, John E.}, year={1993}, month={Jul}, pages={181–185} } @article{weerasinghe_gadsby_1992, title={The presence of glandular kallikrein in rabbit fetal placental conditioned medium.}, volume={131}, ISSN={0013-7227 1945-7170}, url={http://dx.doi.org/10.1210/endo.131.4.1396322}, DOI={10.1210/endo.131.4.1396322}, abstractNote={Glandular (tissue) kallikreins are known to be involved in the posttranslational modification of protein hormones and growth factors in addition to their classical role as the bradykinin-releasing enzyme in tissues. They have been shown to be present in many tissues, such as the pancreas, salivary glands, pituitary, and testes. The objective of this study was to investigate the presence of kallikrein in the rabbit placenta. Day 21 pregnant rabbit fetal placentae were teased apart in medium 199, washed thoroughly, and incubated in fresh medium for 6 h at 37 C. The resulting placental conditioned medium (FPI) was found to have 31.35 +/- 4.3 U glandular kallikrein-like amidolytic activity/mg protein toward the chromogenic peptide substrate S-2266 (1 U is defined as the amount of p-nitroaniline liberated by 10 ng rat urinary kallikrein). Using an enzyme-linked immunosorbent assay with sheep serum raised against rat urinary kallikrein, the glandular kallikrein concentration of FPI was estimated to be 4.56 +/- 0.857 micrograms/mg protein. Upon Western blot analysis, FPI gave a positive band of 45,000 in the presence of beta-mercaptoethanol. In the absence of beta-mercaptoethanol, a band of 138,000 was observed, indicating that in FPI, kallikrein is present bound to a high mol wt binding protein. These results strongly indicate the presence of glandular kallikrein in rabbit fetal placentae.}, number={4}, journal={Endocrinology}, publisher={The Endocrine Society}, author={Weerasinghe, K M and Gadsby, J E}, year={1992}, month={Oct}, pages={1777–1781} } @article{gadsby_smith_almond_1991, title={Acute stimulatory effects of prostaglandin F2α on serum progesterone concentrations in pregnant and pseudopregnant pigs}, volume={41}, ISSN={0090-6980}, url={http://dx.doi.org/10.1016/0090-6980(91)90049-l}, DOI={10.1016/0090-6980(91)90049-l}, abstractNote={The objective of this study was to investigate whether PGF2 alpha, administered to pregnant and pseudopregnant gilts in vivo, would cause an acute increase in serum progesterone concentrations prior to luteolysis. Pregnant (n = 9) and pseudopregnant (n = 4) gilts were fitted with a jugular vein cannula on day 40, were treated with 3 ml vehicle (control) i.m. on day 42 and with 15 mg PGF2 alpha on day 45. Blood samples were collected at frequent (5 and 15 min) intervals from 1 h before until 1 h after control and PGF2 alpha injections, at 15 min intervals for 4 h, and then at 5, 6, 9, 21, 33, 45 and 57 h post injection. Progesterone was measured by radioimmunoassay (RIA) in all samples. Porcine LH was measured by RIA in samples collected frequently in the 1 h pre- and 1 h post-injection periods. Serum progesterone concentrations were unchanged in both pregnant and pseudopregnant animals in response to control injection on day 42. However, in both pregnant and pseudopregnant gilts, PGF2 alpha injection on day 45 resulted in an acute increase (approximately 75-80% above pre-treatment levels; p less than 0.05) in serum progesterone lasting approximately 1 h, followed by a return to pre-treatment levels by 2 h, and then a decline to 1 ng/ml or less by 45-57 h (pregnant) or 21-57 h (pseudopregnant), associated with luteolysis. Serum LH concentrations were unchanged between 1 h pre- and post-treatment periods in response to either control or PGF2 alpha-treatment, in both pregnant and pseuodpregnant gilts. These results indicate that PGF2 alpha-injection produces a rapid and transient increase in serum progesterone concentrations which may result from a rapid and direct stimulatory action of PGF2 alpha on porcine luteal cell progesterone synthesis/secretion in vivo.}, number={5}, journal={Prostaglandins}, publisher={Elsevier BV}, author={Gadsby, J.E. and Smith, C.A. and Almond, G.W.}, year={1991}, month={May}, pages={419–432} } @article{hunzicker-dunn_chen_jackiw_gadsby_bill_labarbera_miller_landis keyes_1991, title={Luteal Enzymes of the Luteinizing Hormone and β-Adrenergic Signal Transduction Pathways in Hypophysectomized Rabbits do not Require Pituitary Hormone Support}, volume={44}, ISSN={0006-3363 1529-7268}, url={http://dx.doi.org/10.1095/biolreprod44.4.609}, DOI={10.1095/biolreprod44.4.609}, abstractNote={Experiments were conducted to determine whether continuous pituitary hormone support is required for expression of the LH and beta-adrenergic cAMP signal transduction pathways in rabbit CL during pseudopregnancy. Parameters of the LH and catecholamine cAMP signal transduction pathways in CL of estrogen-treated hypophysectomized rabbits were compared to those of pituitary-intact rabbits. Results showed that each of the parameters of the LH and beta-adrenergic cAMP signal transduction pathways was retained in CL taken from estrogen-treated pseudopregnant rabbits that had been hypophysectomized for as long as 13 days at levels not significantly different from those of estrogen-treated pituitary-intact rabbits. These included luteal basal, and LH-, epinephrine-, and fluoride-stimulated adenylyl cyclase activities; total luteal cAMP levels; the number and affinity of cAMP-dependent protein kinase regulatory subunit cAMP binding sites; binding activity of the type I and type II regulatory subunits; and the amount of catalytic subunit protein of cAMP-dependent protein kinase. We conclude that expression of the proteins of the cAMP signal pathway for LH and beta-adrenergic hormones in CL of estrogen-treated rabbits does not require pituitary hormone support.}, number={4}, journal={Biology of Reproduction}, publisher={Oxford University Press (OUP)}, author={Hunzicker-Dunn, Mary and Chen, Anthony and Jackiw, Victoria and Gadsby, John E. and Bill, Charles H., II and LaBarbera, Andrew R. and Miller, Josephine B. and Landis Keyes, P.}, year={1991}, month={Apr}, pages={609–619} } @article{gadsby_balapure_britt_fitz_1990, title={Prostaglandin F2α Receptors on Enzyme-Dissociated Pig Luteal Cells throughout the Estrous Cycle*}, volume={126}, ISSN={0013-7227 1945-7170}, url={http://dx.doi.org/10.1210/endo-126-2-787}, DOI={10.1210/endo-126-2-787}, abstractNote={A deficiency of luteal cell prostaglandin F2α (PGF2α) receptors might help explain the well documented refractoriness of pig corpora lutea to the luteolytic effects of PGF2α administered in vivo before day 12 of the estrous cycle. Accordingly, experiments were conducted to measure the levels of [3H] PGF2α-binding sites/receptors on collagenase-dispersed pig luteal cells taken at different stages of the estrous cycle. Pig corpora lutea were obtained surgically at various stages of the estrous cycle and dissociated with collagenase in medium 199. Dissociated mixed luteal cells (-5-15 X 104 large luteal cells/ tube) were assayed for [3H]PGF2a-binding activity by saturation (Scatchard) analysis. In preliminary experiments it was determined that PGF2o binding was maximal after incubation for 45 min at 30 C in assay buffer of pH 5.75. Additionally, it was determined that [3H]PGF2α binding was displaceable by PGF2α = PGD2 > PGE2 > 13,14-dihydro-15-keto-PGF2α. Other eicosanoids did not inhibit [3H]PGF2α binding. ...}, number={2}, journal={Endocrinology}, publisher={The Endocrine Society}, author={Gadsby, J. E. and Balapure, A. K. and Britt, J. H. and Fitz, T. A.}, year={1990}, month={Feb}, pages={787–795} } @article{gadsby_1989, title={Control of corpus luteum function in the pregnant rabbit}, volume={37}, journal={Journal of Reproduction and Fertility Supplement}, author={Gadsby, J.E.}, year={1989}, pages={45–54} } @article{gadsby_lancaster_1989, title={Rabbit placental-conditioned medium stimulates progesterone accumulation by granulosa-lutein cells in culture: preliminary characterization of a placental luteotropic hormone}, volume={40}, ISSN={0006-3363 1529-7268}, url={http://dx.doi.org/10.1095/biolreprod40.2.239}, DOI={10.1095/biolreprod40.2.239}, abstractNote={The rabbit fetal placenta plays an important physiological role in luteal maintenance in pregnancy, probably via the secretion of an unidentified placental "luteotropin." The objective of these studies was to examine conditioned medium from fetal placental-tissue incubations (FPI) for the presence of placental luteotropic hormones/factors, using the stimulation of progesterone accumulation by rabbit granulosa-lutein cells in culture, as an in vitro luteotropic bioassay. Progesterone accumulation by rabbit granulosa-lutein cells (during 5 days of culture) was increased (compared with controls), 1.5-fold by 10(-8) M estradiol-17 beta (E2) and 11.5-fold by 100 ng/ml luteinizing hormone (oLH). FPI stimulated progesterone accumulation (approximately 3-fold) and this was further increased in the presence of E2 (FPI + E2; approximately 6-fold). Luteotropic bioactivity in FPI (+ E2) was retained after dialysis (6000-8000 MW cutoff; 7.8-fold) and heating (90-95 degrees C for 1 h; 7.5-fold), but was destroyed after incubation with trypsin (1 mg/ml, 1 h at 37 degrees C; 0.9-fold). Media conditioned with skeletal muscle (1.2-fold), heart (1.6-fold), liver (1.5-fold), and uterus (0.5-fold) and 5-10% serum (less than 1-fold), from pseudopregnant rabbits, had little or no luteotropic bioactivity. These data indicate that FPI contains a luteotropic hormone/factor that is probably a heat-stable, trypsin-sensitive, protein/peptide of greater than 6000-8000 MW that acts in synergy with E2 to promote granulosa-lutein cell steroidogenesis. This placental hormone/factor is a good candidate for the elusive rabbit placental luteotropin.}, number={2}, journal={Biology of Reproduction}, publisher={Oxford University Press (OUP)}, author={Gadsby, J.E. and Lancaster, M.}, year={1989}, month={Feb}, pages={239–249} } @inbook{keyes_gadsby_1987, title={Role of Estrogen and the Placenta in the Maintenance of the Rabbit Corpus Luteum}, ISBN={9781468453973 9781468453959}, ISSN={0065-2598}, url={http://dx.doi.org/10.1007/978-1-4684-5395-9_17}, DOI={10.1007/978-1-4684-5395-9_17}, abstractNote={The rabbit is among those species in which the placenta secretes low or physiologically insignificant quantities of progesterone, and therefore, the corpora lutea must remain steroidogenically active throughout gestation (Hilliard, 1973; Thau and Lanman, 1974). If the young embryo is to survive, it must transmit a signal that in some way halts or overrides incipient luteal regression, reflected in declining serum progesterone values by 15 days after ovulation in non-pregnant animals (Keyes et al., 1983a). The subject of this manuscript is an exploration of the mechanisms that are responsible for placental maintenance of luteal function. We begin with a brief summary of the literature, setting the stage for the specific hypotheses and experiments reported herein.}, booktitle={Advances in Experimental Medicine and Biology}, publisher={Springer US}, author={Keyes, P. Landis and Gadsby, John E.}, year={1987}, pages={361–378} } @article{gadsby_keyes_schwartz_bill_lucchesi_1985, title={Do Catecholamines Play a Physiologic Role in Regulating Corpus Luteum Function in the Pseudopregnant Rabbit?}, volume={32}, DOI={10.1095/biolreprod32.4.907}, abstractNote={In these studies the beta-adrenergic receptor antagonist propranolol was administered to estrogen-treated hypophysectomized pseudopregnant rabbits in vivo, and serum progesterone concentrations were measured to monitor luteal function. In Experiment 1, which was designed to determine an effective dose of propranolol, 1 mg/(kg X h) s.c. propranolol for 3 h (integral of 80 ng/ml in serum) gave an adequate level of beta-adrenergic receptor blockade, i.e., a 1000-fold inhibition of the blood pressure/isoproterenol dose-response relationship. In Experiment 2, "acute" administration of propranolol (P; 1 mg/(kg X h) s.c.) or saline (control, C) for 24 h on Days 7-8, 10-11, and 13-14 of pseudopregnancy did not produce any marked differences in serum progesterone concentrations in P or C animals on any of the days tested, although hourly fluctuations were observed. In Experiment 3, "chronic" (4-day) treatment with propranolol was achieved by the use of propranolol-containing pellets placed s.c. (integral of 200-600 ng/ml in serum), on Days 13-17. Control animals received pellets of vehicle only. Serum progesterone concentrations were very similar in P and C animals throughout the period of treatment (Days 13-17) and on Days 18 and 20. We conclude that endogenous catecholamines play no major role in regulating luteal steroidogenesis or corpus luteum regression in the pseudopregnant rabbit.}, number={4}, journal={Biology of Reproduction}, author={Gadsby, J.E. and Keyes, P.L. and Schwartz, T.S. and Bill, C.H., II. and Lucchesi, B.}, year={1985}, pages={907–915} } @inproceedings{hunzicker-dunn_gadsby_bill_labarbera_keyes_miller_1985, place={Champaign, Illinois}, title={Maintenance of rabbit luteal LH and catecholamine responsive adenylyl cyclase and cyclic AMP content does not require pituitary support}, booktitle={Proceedings of the Fifth Ovarian Workshop}, publisher={Ovarian Workshops}, author={Hunzicker-Dunn, M. and Gadsby, J.E. and Bill, C.H., II and LaBarbera, A.R. and Keyes, P.L. and Miller, J.B.}, editor={Ryan, R.J. and Toft, D.O.Editors}, year={1985}, pages={89–94} } @article{gadsby_landis keyes_1984, title={Control of Corpus Luteum Function in the Pregnant Rabbit: Role of the Placenta (“Placental Luteotropin”) in Regulating Responsiveness of Corpora Lutea to Estrogen}, volume={31}, ISSN={0006-3363 1529-7268}, url={http://dx.doi.org/10.1095/biolreprod31.1.16}, DOI={10.1095/biolreprod31.1.16}, abstractNote={Experiments were performed to examine the interaction between estrogen and "placental luteotropin," the two luteotropins thought to be required for corpus luteum maintenance in the pregnant rabbit. Experiment 1 was designed to determine whether estrogen alone was luteotropic in the absence of "placental luteotropin." Pregnant rabbits were assigned to the following groups: Group A, sham hysterectomy; Group B, hysterectomy; Group C, hysterectomy plus estradiol on Day 20; and Group D, hysterectomy plus estradiol on Day 22. "Placental luteotropin" was removed on Day 21 of pregnancy by hysterectomy and estrogen was administered via an estradiol-filled Silastic implant which was placed s.c. before (Day 20, Group C) or after (Day 22, Group D) hysterectomy. Daily blood samples were taken for radioimmunoassay of serum progesterone and estradiol concentrations. Corpus luteum weights were measured at autopsy on Day 27. Hysterectomy caused serum progesterone concentrations to fall rapidly from 13 +/- 1 ng/ml on Day 21 to 2 +/- 1 ng/ml on Day 23, and to 1 ng/ml or less on Days 24-27. In sham hysterectomized rabbits (Group A), pregnancy was maintained and serum progesterone concentrations remained elevated at 9-15 ng/ml throughout (Days 20-27). Estradiol treatment (Groups C and D) did not prevent or reverse luteal regression induced by hysterectomy and serum progesterone concentrations declined in a similar fashion to Group B. Serum estradiol concentrations were 4-8 pg/ml in all groups and did not vary substantially with stage of pregnancy or treatment.(ABSTRACT TRUNCATED AT 250 WORDS)}, number={1}, journal={Biology of Reproduction}, publisher={Oxford University Press (OUP)}, author={Gadsby, John E. and Landis Keyes, P.}, year={1984}, month={Aug}, pages={16–24} } @inbook{keyes_yuh_bill_gadsby_1984, title={New Perspectives on the Endocrine Regulation of the Rabbit Corpus Luteum}, ISBN={9781468499629 9781468499605}, url={http://dx.doi.org/10.1007/978-1-4684-9960-5_19}, DOI={10.1007/978-1-4684-9960-5_19}, booktitle={Hormonal Control of the Hypothalamo-Pituitary-Gonadal Axis}, publisher={Springer US}, author={Keyes, P. Landis and Yuh, Khe-Ching M. and Bill, Charles H. and Gadsby, John E.}, year={1984}, pages={273–288} } @article{gadsby_keyes_bill_1983, title={Control of Corpus Luteum Function in the Pregnant Rabbit: Role of Estrogen and Lack of a Direct Luteotropic Role of the Placenta}, volume={113}, ISSN={0013-7227 1945-7170}, url={http://dx.doi.org/10.1210/endo-113-6-2255}, DOI={10.1210/endo-113-6-2255}, abstractNote={The corpus luteum is essential for pregnancy maintenance in the rabbit and appears to require two luteotropins: estrogen from ovarian follicles and a placental luteotropic factor. We have investigated the role of the placental luteotropic factor in maintaining corpus luteum function in the pregnant rabbit in the absence of estrogen. In Exp 1, follicular estrogen was withdrawn on day 21 of pregnancy by ovulating follicles with 10 IU hCG. In Exp 2, estrogen was withdrawn in hypophysectomized pregnant rabbits on day 21 by removing an estradiol (E2) implant. In the presence of this estrogen implant, luteal function and pregnancy are maintained after hypophysectomy, performed on day 4 of pregnancy. In both experiments, fetoplacental viability was ensured by treating the rabbits with medroxyprogesterone acetate (MPA). In both Exp 1 and 2, withdrawal of estrogen on day 21 of pregnancy caused a dramatic decline in serum progesterone concentrations by day 22. Serum progesterone concentrations remained low, and corpora lutea regressed, although viable fetuses were maintained with MPA. In animals not receiving MPA, estrogen withdrawal caused the loss of luteal function, followed by abortion on days 23-24. In contrast, estrogen replacement (via E2 implant) on day 22 in Exp 1 was fully capable of restoring serum progesterone concentrations to pretreatment values on days 24-27 in MPA-treated rabbits. In rabbits not receiving MPA, estrogen replacement also restored serum progesterone concentrations and prevented abortion. These results provide further evidence that estrogen is essential for normal luteal function in the pregnant rabbit. In the absence of estrogen, the rabbit placenta maintained by the progestagen MPA has no direct luteotropic activity.}, number={6}, journal={Endocrinology}, publisher={The Endocrine Society}, author={Gadsby, John E. and Keyes, P. Landis and Bill, Charles H.}, year={1983}, month={Dec}, pages={2255–2262} } @inbook{flint_burton_gadsby_heap_sheldrick_1983, title={EMBRYONIC STEROID SYNTHESIS AND LUTEAL OXYTOCIN PRODUCTION: CONTROLLING MECHANISMS FOR THE MATERNAL RECOGNITION OF PREGNANCY}, ISBN={9780080307718}, url={http://dx.doi.org/10.1016/b978-0-08-030771-8.50142-x}, DOI={10.1016/b978-0-08-030771-8.50142-x}, booktitle={Hormonal Steroids}, publisher={Elsevier}, author={Flint, A.P.F. and Burton, R.D. and Gadsby, J.E. and Heap, R.B. and Sheldrick, E.L.}, year={1983}, pages={973–978} } @inbook{keyes_gadsby_yuh_bill_1983, place={Baltimore, MD}, series={International Review of Physiology}, title={The Corpus Luteum}, volume={27}, booktitle={Reproductive Physiology IV}, publisher={University Park Press}, author={Keyes, P.L. and Gadsby, J.E. and Yuh, K.-C.M. and Bill, C.H., II}, editor={Greep, R.Editor}, year={1983}, pages={59–97}, collection={International Review of Physiology} } @inbook{gadsby_1982, title={Steroid Hormones in Blastocyst Tissue, Uterine Flushings, and Endometrium of Pig, Sheep, and Cow}, ISBN={9783642678929 9783642678905}, url={http://dx.doi.org/10.1007/978-3-642-67890-5_15}, DOI={10.1007/978-3-642-67890-5_15}, booktitle={Proteins and Steroids in Early Pregnancy}, publisher={Springer Berlin Heidelberg}, author={Gadsby, J. E.}, year={1982}, pages={173–182} } @inbook{heap_gadsby_rice_perry_1982, title={The Synthesis of Steroids and Proteins in the Pig Blastocyst}, ISBN={9783642678929 9783642678905}, url={http://dx.doi.org/10.1007/978-3-642-67890-5_14}, DOI={10.1007/978-3-642-67890-5_14}, booktitle={Proteins and Steroids in Early Pregnancy}, publisher={Springer Berlin Heidelberg}, author={Heap, R. B. and Gadsby, J. E. and Rice, Catherine and Perry, J. S.}, year={1982}, pages={157–171} } @inbook{heap_flint_gadsby_1981, place={New York}, title={Embryonic signals and maternal recognition}, booktitle={Cellular and Molecular aspects of Implantation}, publisher={Plenum Press}, author={Heap, R.B. and Flint, A.P.F. and Gadsby, J.E.}, editor={Glasser, S.R. and Bullock, D.W.Editors}, year={1981}, pages={311–326} } @article{heap_flint_hartmann_gadsby_staples_ackland_hamon_1981, title={Oestrogen production in early pregnancy}, volume={89}, journal={Journal of Endocrinology Supplement}, author={Heap, R.B. and Flint, A.P.F. and Hartmann, P.E. and Gadsby, J.E. and Staples, L.D. and Ackland, N. and Hamon, M.}, year={1981}, pages={77–94} } @inproceedings{heap_flint_gadsby_maule walker_1980, place={Melbourne, Australia}, title={Blastocyst steroids and implantation}, booktitle={Endocrinology 1980: proceedings of the VI International Congress of Endocrinology, Melbourne, Australia, February 10-16, 1980}, publisher={Australian Academy of Science}, author={Heap, R.B. and Flint, A.P.F. and Gadsby, J.E. and Maule Walker, F.M.Saunders}, editor={Cumming, I.A. and Funder, J.W. and Mendelsohn, F.A.O.Editors}, year={1980}, pages={79–82} } @article{gadsby_heap_burton_1980, title={Oestrogen production by blastocyst and early embryonic tissue of various species}, volume={60}, ISSN={1470-1626 1741-7899}, url={http://dx.doi.org/10.1530/jrf.0.0600409}, DOI={10.1530/jrf.0.0600409}, abstractNote={Oestrogen synthesis by the early embryo in vitro was studied with tissue from pigs, sheep, cows, roe deer, ferrets, cats, rabbits and a plains viscacha. Definitive evidence for aromatase activity and oestrogen synthesis in preimplantation trophoblast was obtained for the pig with the formation of oestrone, oestradiol-17 beta and oestradiol-17 alpha from 3H-labelled androstenedione and dehydroepiandrosterone. Aromatase activity was appreciably lower in all other species studied, and labelled oestrogens were recovered only from incubations of allantochorionic tissue of roe deer, recovered shortly after implantation, and from pooled samples of early embryonic tissue of cows. High aromatase activity in preimplantation trophoblast of pigs was associated with the maternal recognition of pregnancy and the occurrence of superficial implantation in this species.}, number={2}, journal={Reproduction}, publisher={Bioscientifica}, author={Gadsby, J. E. and Heap, R. B. and Burton, R. D.}, year={1980}, month={Nov}, pages={409–417} } @inbook{flint_burton_gadsby_saunders_heap_1979, place={Amsterdam}, series={Ciba Foundation Symposium}, title={Blastocyst oestrogen synthesis and the maternal recognition of pregnancy}, booktitle={Maternal Recognition of Pregnancy}, publisher={Excerpta Medica}, author={Flint, A.P. F. and Burton, R.D. and Gadsby, J.E. and Saunders, P.T.K. and Heap, R.B.}, editor={Whelan, J.Editor}, year={1979}, pages={209–228}, collection={Ciba Foundation Symposium} } @inproceedings{flint_gadsby_heap_1979, place={London, U.K}, title={Blastocyst steroids: their synthesis and action}, volume={8}, booktitle={Research on steroids}, publisher={Academic Press}, author={Flint, A.P.F. and Gadsby, J.E. and Heap, R.B.}, editor={Klopper, A. and Lerner, L. and van der Molen, H.J. and Sciarra, F.Editors}, year={1979}, pages={3–10} } @article{heap_flint_gadsby_rice_1979, title={Hormones, the early embryo and the uterine environment}, volume={55}, ISSN={1470-1626 1741-7899}, url={http://dx.doi.org/10.1530/jrf.0.0550267}, DOI={10.1530/jrf.0.0550267}, abstractNote={Studies using in-vitro culture (Brinster, 1969; Whitten, 1970), in-vitro microsurgery (Gardner, 1968), and embryo transfer to ectopic sites (Fawcett, 1950; Kirby, 1962, 1969) have shown that before blastulation the mammalian ovum develops independently of its uterine environment. After this time the blastocyst becomes less autonomous and development depends increasingly on the local environment. Evidence for dependence upon the uterine milieu also arises from experiments on the transfer of embryos between donor and recipient animals and the transfer of blastocysts to ectopic sites, and from investigations of the phenomenon of delayed implantation. In this paper we consider the nature of the interaction between the endometrium and the blastocyst and indicate where interception may inhibit maternal or embryonic signals which are indispensible for implantation and the establishment of pregnancy.}, number={1}, journal={Reproduction}, publisher={Bioscientifica}, author={Heap, R. B. and Flint, A. P. F. and Gadsby, J. E. and Rice, C.}, year={1979}, month={Jan}, pages={267–275} } @article{heap_flint_gadsby_1979, title={ROLE OF EMBRYONIC SIGNALS IN THE ESTABLISHMENT OF PREGNANCY}, volume={35}, ISSN={1471-8391 0007-1420}, url={http://dx.doi.org/10.1093/oxfordjournals.bmb.a071559}, DOI={10.1093/oxfordjournals.bmb.a071559}, abstractNote={Journal Article ROLE OF EMBRYONIC SIGNALS IN THE ESTABLISHMENT OF PREGNANCY Get access R B HEAP, MA PhD, R B HEAP, MA PhD Agriculatural Research Council Institute of Animal Physiology BabrahamCambridge Search for other works by this author on: Oxford Academic PubMed Google Scholar A P FLINT, PhD, A P FLINT, PhD Agriculatural Research Council Institute of Animal Physiology BabrahamCambridge Search for other works by this author on: Oxford Academic PubMed Google Scholar J E GADSBY, PhD J E GADSBY, PhD Agriculatural Research Council Institute of Animal Physiology BabrahamCambridge Search for other works by this author on: Oxford Academic PubMed Google Scholar British Medical Bulletin, Volume 35, Issue 2, May 1979, Pages 129–135, https://doi.org/10.1093/oxfordjournals.bmb.a071559 Published: 01 May 1979}, number={2}, journal={British Medical Bulletin}, publisher={Oxford University Press (OUP)}, author={Heap, R B and Flint, A P and Gadsby, J E}, year={1979}, month={May}, pages={129–135} } @inbook{flint_gadsby_heap_1978, place={Paris, France}, title={Blastocyst steroids: their synthesis and actions.}, booktitle={L'implantation de l'oeuf : colloque de la Société nationale pour l'étude de la stérilité et de la fécondité}, publisher={Thomas. Masson}, author={Flint, A.P. F. and Gadsby, J.E. and Heap, R.B.}, editor={Du Mesnil du Buisson, F and Psychoyos, A. and Thomas, K.Editors}, year={1978}, pages={177–179} } @inbook{gadsby_heap_1978, place={New York}, title={Steroid hormones and their synthesis in the early embryo}, booktitle={Novel Aspects of Reproductive Physiology}, publisher={SP Medical and Scientific Books}, author={Gadsby, J.E. and Heap, R.B.}, editor={Spilman, Eds C.H. and Wilks, J.W.Editors}, year={1978}, pages={263–285} } @inbook{heap_perry_burton_gadsby_wyatt_jenkin_1977, place={Canberra}, title={Blastocyst steroidogenesis and embryo-maternal interactions in the establishment of pregnancy}, booktitle={Reproduction and Evolution : proceedings of the Fourth Symposium on Comparative Biology of Reproduction, held in Canberra, December, 1976}, publisher={Australian Academy of Sciences}, author={Heap, R.B. and Perry, J.S. and Burton, R.D. and Gadsby, J.E. and Wyatt, C.J. and Jenkin, G.}, editor={Calaby, J.H. and Tyndale-Biscoe, C.H.Editors}, year={1977}, pages={341–347} } @article{heap_perry_gadsby_burton_wyatt_1977, title={Endocrine Activities and Protein Synthesis in the Early Blastocyst}, volume={5}, ISSN={0300-5127 1470-8752}, url={http://dx.doi.org/10.1042/bst0050457}, DOI={10.1042/bst0050457}, abstractNote={Conference Article| April 01 1977 Endocrine Activities and Protein Synthesis in the Early Blastocyst R. BRIAN HEAP; R. BRIAN HEAP 1A.R.C. Institute of Animal Physiology, Babraham, Cambridge CB2 4AT, U.K. Search for other works by this author on: This Site PubMed Google Scholar JOHN S. PERRY; JOHN S. PERRY 2A.R.C. Institute of Animal Physiology, Babraham, Cambridge CB2 4AT, U.K. Search for other works by this author on: This Site PubMed Google Scholar JOHN E. GADSBY; JOHN E. GADSBY 3A.R.C. Institute of Animal Physiology, Babraham, Cambridge CB2 4AT, U.K. Search for other works by this author on: This Site PubMed Google Scholar ROBERT D. BURTON; ROBERT D. BURTON 4A.R.C. Institute of Animal Physiology, Babraham, Cambridge CB2 4AT, U.K. Search for other works by this author on: This Site PubMed Google Scholar CATHERINE WYATT CATHERINE WYATT 5A.R.C. Institute of Animal Physiology, Babraham, Cambridge CB2 4AT, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1977) 5 (2): 457–458. https://doi.org/10.1042/bst0050457 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation R. BRIAN HEAP, JOHN S. PERRY, JOHN E. GADSBY, ROBERT D. BURTON, CATHERINE WYATT; Endocrine Activities and Protein Synthesis in the Early Blastocyst. Biochem Soc Trans 1 April 1977; 5 (2): 457–458. doi: https://doi.org/10.1042/bst0050457 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search © 1977 Biochemical Society1977 Article PDF first page preview Close Modal You do not currently have access to this content.}, number={2}, journal={Biochemical Society Transactions}, publisher={Portland Press Ltd.}, author={Heap, R. Brian and Perry, John S. and Gadsby, John E. and Burton, Robert D. and Wyatt, Catherine}, year={1977}, month={Apr}, pages={457–458} } @article{perry_heap_burton_gadsby_1976, title={Endocrinology of the blastocyst and its role in the establishment of pregnancy}, volume={Suppl. 25}, journal={Journal of Reproduction and fertility}, author={Perry, J.S. and Heap, R.B. and Burton, R.D. and Gadsby, J.E.}, year={1976}, pages={85–104} } @article{heap_holdsworth_gadsby_laing_walters_1976, title={Pregnancy Diagnosis in the Cow from Milk Progesterone Concentration}, volume={132}, ISSN={0007-1935}, url={http://dx.doi.org/10.1016/s0007-1935(17)34582-7}, DOI={10.1016/s0007-1935(17)34582-7}, abstractNote={A direct, rapid radioimmunoassay was developed to measure progesterone in a small sample of milk taken from full milk collected at afternoon milking. Samples were preserved with potassium dichromate and mercuric chloride and transported to the laboratory for assay by a semi-automated procedure. Milk progesterone concentrations were significantly higher in pregnant cows compared with those in non-pregnant cows at 21, 24, 28, 42 and 60 days after insemination. The concentrations were greater in full milk taken at afternoon milking than in first milk taken at morning milking. The concentration of progesterone in milk was found to be correlated with fat content in samples with low progesterone values but not in those with high progesterone values. The success rate of the pregnancy test from a single milk sample 21, 24, 28 or 42 days after insemination ranged from 77·5 to 85·8% for pregnant cows and 85·7 to 100% for non-pregnant cows. The highest success rate was found at 24 days when 142 of 176 pregnant cows (80%) and 25 of 25 non-pregnant (100%) were correctly diagnosed. The use of paired instead of single milk samples gave negligible improvement in success rate. The accuracy of the test in three herds was compared and the incidence of false positive results was analyzed.}, number={5}, journal={British Veterinary Journal}, publisher={Elsevier BV}, author={Heap, R.B. and Holdsworth, R.J. and Gadsby, J.E. and Laing, J.A. and Walters, D.E.}, year={1976}, month={Sep}, pages={445–464} } @article{heap_perry_gadsby_burton_1975, title={Endocrine Activities of the Blastocyst and Early Embryonic Tissue in the Pig}, volume={3}, ISSN={0300-5127 1470-8752}, url={http://dx.doi.org/10.1042/bst0031183}, DOI={10.1042/bst0031183}, abstractNote={day 10 (Fig. 2) . At this time no stimulation of total protein synthesis is detectable (Kaye et al., 1973). This might suggest that thymidine kinase is a critical enzyme in the oestrogeninduced stimulation of DNA synthesis, though the kinetics of enzyme stimulation do not really support such a view (Fig. 1). Detectable stimulation of DNA synthesis occurs after intraperitoneal injection of only 5Opg of oestradiol-178, though a dose of 50ng is required for maximum response (Kaye et al., 1972). In contrast, detectable stimulation of thymidine kinase activity requires a dose of 5ng of oestradioLl7g and maximum response is achieved with 100ng. This may simply represent differences in the sensitivity of the two assay procedures. In conclusion, the mechanism(s) by which steroid hormones influence uterine DNA synthesis is slowly succumbing to investigation. However, the nature of the changes in control of DNA synthesis associated with such complications as the onset of pregnancy or the development of uterine carcinoma still presents a considerable challenge.}, number={6}, journal={Biochemical Society Transactions}, publisher={Portland Press Ltd.}, author={Heap, R. Brian and Perry, John S. and Gadsby, E. John and Burton, Robert D.}, year={1975}, month={Dec}, pages={1183–1188} } @article{gadsby_heap_powell_walters_1972, title={Diagnosis of pregnancy and of the number of foetuses in sheep from plasma progesterone concentrations}, volume={90}, ISSN={0042-4900 2042-7670}, url={http://dx.doi.org/10.1136/vr.90.12.339}, DOI={10.1136/vr.90.12.339}, number={12}, journal={Veterinary Record}, publisher={BMJ}, author={Gadsby, J. and Heap, R. and Powell, D. and Walters, D.}, year={1972}, month={Mar}, pages={339–342} }