@article{laws_hotchkiss_ferrell_jayaraman_mills_modic_tinfo_fraites_stoker_cooper_2009, title={Chlorotriazine Herbicides and Metabolites Activate an ACTH-dependent Release of Corticosterone in Male Wistar Rats}, volume={112}, ISSN={["1096-6080"]}, DOI={10.1093/toxsci/kfp190}, abstractNote={Previously, we reported that atrazine (ATR) alters steroidogenesis in male Wistar rats resulting in elevated serum corticosterone (CORT), progesterone, and estrogens. The increase in CORT indicated that this chlorotriazine herbicide may alter the hypothalamic-pituitary-adrenal axis. This study characterizes the temporal changes in adrenocorticotropic hormone (ACTH), CORT, and P4 in male Wistar rats following a single dose of ATR (0, 5, 50, 100, and 200 mg/kg), simazine (SIM; 188 mg/kg), propazine (PRO; 213 mg/kg), or primary metabolites, deisopropylatrazine (DIA; 4, 10, 40, 80, and 160 mg/kg), deethylatrazine (DEA; 173 mg/kg), and diamino-s-chlorotriazine (DACT; 3.37, 33.7, 67.5, and 135 mg/kg). The maximum dose for each chemical was the molar equivalent of ATR (200 mg/kg). Significant increases in plasma ACTH were observed within 15 min, following exposure to ATR, SIM, PRO, DIA, or DEA. Dose-dependent elevations in CORT and progesterone were also observed at 15 and 30 min post-dosing with these compounds indicating an activation of adrenal steroidogenesis. Measurement of the plasma concentrations of the parent compounds and metabolites confirmed that ATR, SIM, and PRO are rapidly metabolized to DACT. Although DACT had only minimal effects on ACTH and steroid release, dosing with this metabolite resulted in plasma DACT concentrations that were 60-fold greater than that observed following an equimolar dose of ATR and eightfold greater than equimolar doses of DIA or DEA, indicating that DACT is not likely the primary inducer of ACTH release. Thus, the rapid release of ACTH and subsequent activation of adrenal steroidogenesis following a single exposure to ATR, SIM, PRO, DIA, or DEA may reflect chlorotriazine-induced changes at the level of the brain and/or pituitary.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Laws, Susan C. and Hotchkiss, Michelle and Ferrell, Janet and Jayaraman, Saro and Mills, Lesley and Modic, Walker and Tinfo, Nicole and Fraites, Melanie and Stoker, Tammy and Cooper, Ralph}, year={2009}, month={Nov}, pages={78–87} }
 @article{laws_webster_miller_1990, title={ESTRADIOL ALTERS THE EFFECTIVENESS OF GONADOTROPIN-RELEASING HORMONE (GNRH) IN OVINE PITUITARY CULTURES - GNRH RECEPTORS VERSUS RESPONSIVENESS TO GNRH}, volume={127}, ISSN={["0013-7227"]}, DOI={10.1210/endo-127-1-381}, abstractNote={17 beta-Estradiol (E) rapidly (5-12 h) induced ovine pituitary cultures to increase their binding of des-Gly10-[D-Ala6] GnRH ethylamide by 2.5- to 4.5-fold. The ED50 for E was near 0.1 nM. Scatchard analysis indicated that E increased binding by increasing receptors for GnRH. GnRH-stimulated release of LH increased 2-fold along with the increase in GnRH receptors, but heightened responsiveness to GnRH disappeared after 27 h of E treatment even though GnRH receptors remained elevated. These data are consistent with the concepts that 1) E increased GnRH receptors, which initially enhanced gonadotroph responsiveness to GnRH, and 2) E subsequently nullified the increased response to GnRH by blocking a mechanism of LH secretion not associated with GnRH receptor number. Further support for this hypothesis came from studies with porcine follicular inhibin. Inhibin in ovine pituitary culture concomitantly increased GnRH receptors by 5-fold and GnRH-stimulated LH secretion by 2-fold. Inhibin maintained both effects long term (48 h). When E was added along with inhibin, the increase in GnRH receptor number became greater than with either hormone alone (7-fold increase at 48 h), but the initial increase in GnRH-stimulated LH secretion was fully inhibited by E at 48 h. The increase in GnRH receptors caused by E may be important physiologically to help create the preovulatory LH surge; the delayed inhibitory action of E on GnRH-stimulated LH secretion may limit the LH surge.}, number={1}, journal={ENDOCRINOLOGY}, author={LAWS, SC and WEBSTER, JC and MILLER, WL}, year={1990}, month={Jul}, pages={381–386} }
 @article{laws_beggs_webster_miller_1990, title={INHIBIN INCREASES AND PROGESTERONE DECREASES RECEPTORS FOR GONADOTROPIN-RELEASING HORMONE IN OVINE PITUITARY CULTURE}, volume={127}, ISSN={["0013-7227"]}, DOI={10.1210/endo-127-1-373}, abstractNote={Treatments (48 h) with highly purified bovine or porcine inhibins (10 ng/ml) induced ovine pituitary cells to increase their binding for des-Gly10-[D-Ala6]LHRH-ethylamide by 3.6- and 5-fold, respectively. Studies with less pure inhibin from porcine follicles showed that increased binding could reach 7-fold within 48 h and was due to higher numbers of receptors for GnRH. The 48-h increase in GnRH receptors was linear with time and was rapidly reversible, since removal of inhibin at 24 h decreased GnRH binding below control levels at 48 h. Inhibin (bovine or porcine) also increased GnRH-stimulated secretion of LH by 2-fold. The ED50 for both inhibin actions noted above was in the range of 0.5-2.0 ng/ml (in terms of highly purified bovine inhibin). Progesterone (P) totally counteracted inhibin induction of GnRH binding and GnRH-stimulated LH secretion at 48 h. In the absence of inhibin, P decreased GnRH binding below control levels by as much as 80% within 48 h, but did not affect GnRH-stimulated LH secretion at 48 h. The ED50 for P action was near 1 nM, which is within the physiological range for P during the luteal phase of the sheep estrous cycle. The data suggest that P may act during the luteal phase to decrease receptors for GnRH. The rapid decrease in P during the 48 h before the preovulatory LH surge should permit GnRH receptors to rise under the influence of inhibin (and estradiol) to boost gonadotroph responsiveness to GnRH so the LH surge may occur to its fullest.}, number={1}, journal={ENDOCRINOLOGY}, author={LAWS, SC and BEGGS, MJ and WEBSTER, JC and MILLER, WL}, year={1990}, month={Jul}, pages={373–380} }