@article{su_shafiee-kermani_gore_jia_wu_miller_2007, title={Expression and regulation of the beta-subunit of ovine follicle-stimulating hormone relies heavily on a promoter sequence likely to bind smad-associated proteins}, volume={148}, ISSN={["1945-7170"]}, DOI={10.1210/en.2006-1635}, abstractNote={FSH is essential for normal gonadal function in mammals. Expression of its beta-subunit (FSHB) controls overall production/secretion of FSH and is induced by activin. Studies with ovine FSHB promoter/reporter constructs in L beta T2 gonadotropes show that induction by activin requires a putative Smad binding element in the ovine FSHB promoter (-162AGAC-159). Similar studies reported here show that another site, juxtaposed to the Smad binding element, was also required for 81% activin induction in L beta T2 cells. This site was similar to several that bind proteins known to partner with Smads. When this site (-171ACTgcgtTT-163) was mutated by changing the nucleotides shown in lowercase letters, the resulting ovine-derived construct (mut-oFSHBLuc) was expressed poorly as a transgene in primary mouse gonadotropes (<0.001 times compared with ovine wild-type transgenes). This decrease in expression demonstrated the importance of this site for activin induction and, perhaps, basal expression, although studies with L beta T2 cells did not suggest this latter possibility. Expression of mut-oFSHBLuc in male mouse gonadotropes in vivo was at least 644 times greater than expression in all but one nongonadotrope tissue tested, indicating that mut-oFSHBLuc retained significant gonadotrope-specific expression. An increase in FSHB expression occurs during estrus in mice and is faithfully reproduced with wild-type ovine FSHBLuc transgenes, but not with mut-oFSHBLuc, indicating that the mutated site is needed for this secondary FSH surge. These data suggest that activin gathers Smads and Smad-associated proteins at the -171/-159 promoter region to regulate expression of the ovine FSHB and overall FSH production.}, number={9}, journal={ENDOCRINOLOGY}, author={Su, Pei and Shafiee-Kermani, Farideh and Gore, A. Jesse and Jia, Jingjing and Wu, Joyce C. and Miller, William L.}, year={2007}, month={Sep}, pages={4500–4508} }
 @article{su_wu_sommer_gore_petters_miller_2005, title={Conditional induction of ovulation in mice}, volume={73}, ISSN={["1529-7268"]}, DOI={10.1095/biolreprod.104.039164}, abstractNote={Abstract Follicle-stimulating hormone controls the maturation of mammalian ovarian follicles. In excess, it can increase ovulation (egg production). Reported here is a transgenic doxycycline-activated switch, tested in mice, that produced more FSHB subunit (therefore more FSH) and increased ovulation by the simple feeding of doxycycline (Dox). The transgenic switch was expressed selectively in pituitary gonadotropes and was designed to enhance normal expression of FSH when exposed to Dox, but to be regulated by all the hormones that normally control FSH production in vivo. Feeding maximally effective levels of Dox increased overall mRNA for FSHB and serum FSH by over half in males, and Dox treatment more than doubled the normal ovulation rate of female mice for up to 10 reproductive cycles. Lower levels of Dox increased the number of developing embryos by 30%. Ovarian structure and function appeared normal. In summary, gene switch technology and normal FSH regulation were combined to effectively enhance ovulation in mice. Theoretically, the same strategy can be used with any genetic switch to increase ovulation (or any highly conserved physiology) in any mammal.}, number={4}, journal={BIOLOGY OF REPRODUCTION}, author={Su, P and Wu, JC and Sommer, JR and Gore, AJ and Petters, RM and Miller, WL}, year={2005}, month={Oct}, pages={681–687} }
 @article{gore_philips_miller_bernard_2005, title={Differential regulation of follicle stimulating hormone by activin A and TGFB1 in murine gonadotropes}, volume={3}, journal={Reproductive Biology and Endocrinology}, author={Gore, A. J. and Philips, D. P. and Miller, W. L. and Bernard, D. J.}, year={2005} }
 @article{safwat_ninomiya-tsuji_gore_miller_2005, title={Transforming growth factor beta-activated kinase 1 is a key mediator of ovine follicle-stimulating hormone beta-subunit expression}, volume={146}, ISSN={["1945-7170"]}, DOI={10.1210/en.2005-0457}, abstractNote={FSH, a key regulator of gonadal function, contains a β-subunit (FSHβ) that is transcriptionally induced by activin, a member of the TGFβ-superfamily. This study used 4.7 kb of the ovine FSHβ-promoter linked to luciferase (oFSHβLuc) plus a well-characterized activin-responsive construct, p3TPLuc, to investigate the hypothesis that Smad3, TGFβ-activated kinase 1 (TAK1), or both cause activin-mediated induction of FSH. Overexpression of either Smad3 or TAK1 induced oFSHβLuc in gonadotrope-derived LβT2 cells as much as activin itself. Induction of p3TPLuc by activin is known to require Smad3 activation in many cell types, and this was true in LβT2 cells, where 10-fold induction by activin (2–8 h after activin treatment) was blocked more than 90% by two dominant negative (DN) inhibitors of Smad3 [DN-Smad3 (3SA) and DN-Smad3 (D407E)]. By contrast, 6.5-fold induction of oFSHβLuc by activin (10–24 h after activin treatment) was not blocked by either DN-Smad inhibitor, suggesting that activation of Smad3 did not t...}, number={11}, journal={ENDOCRINOLOGY}, author={Safwat, N and Ninomiya-Tsuji, J and Gore, AJ and Miller, WL}, year={2005}, month={Nov}, pages={4814–4824} }