Hormonal interactions in progesterone regulation of gonadotropin gene expression
The differential regulation of gonadotropin secretion is integral to a properly functioning reproductive system. Transcriptional regulation and secretion of the two gonadotropins diverge during late proestrus and early estrus when LH levels decline with the termination of the preovulatory gonadotropin surge, while FSH remains elevated. Gonadal steroid hormone feedback is a crucial component of the control of gonadotropin synthesis in the pituitary gonadotrope, and progestins may be of particular importance for the secondary FSH surge. In the current study, we have focused on delineating the mechanisms of progestin regulation of the gonadotropin \[Beta\]-subunits. Within the murine FSH\[Beta\] promoter, our studies demonstrated that a FOXL2 element at -350 and a nearby Smad half-site are necessary for both progestin responsiveness and synergy between activin and progestin. In the context of the -300 rat LH\[Beta\] promoter, we found that the -200/-150bp region contributes to basal gene expression, most likely by binding transcriptional activators. Additionally, we contributed to finer mapping of progesterone suppression of basal and GnRH-induced LH\[Beta\] gene expression by identifying a critical segment at the -300/-280bp region of the promoter. Finally, to study the feedback regulation of progesterone in gonadotrope cells in vivo, we created a gonadotrope- specific PRKO: the PRKOLacZ/Flox/LH\[Beta\]-Cre mouse line. Though, our studies did not show any significant impairment of fertility, possibly due to genetic penetrance or mosaicism issues, they serve as preliminary data indicating trends towards lower reproductive function, such as lower number of litters and pups, as well as lower levels of circulating hormones.