Roles of estrogen, progesterone, and gonadotropin-releasing hormone (GnRH) in the control of pituitary GnRH receptor gene expression at the time of the preovulatory gonadotropin surges

Pituitary GnRH receptor (GnRH-R) messenger RNA (mRNA) levels are regulated dynamically during the rat estrous cycle. GnRH-R mRNA levels increase 3-fold on the morning of proestrus and remain elevated throughout the gonadotropin surges, after which they decline rapidly. Because the day of proestrus is characterized by complex changes in the steroidal milieu and increased release of hypothalamic peptides such as GnRH, a series of in vivo steroid replacement and in vitro perifusion studies was used to assess the relative contributions of estrogen (E), progesterone (P), and GnRH to the induction and decline of GnRH-R gene expression during the gonadotropin surges. Steroid replacement studies in ovariectomized (OVX) E-primed rats demonstrated that GnRH-R mRNA levels were elevated before and during the E-induced LH surge (1000-1800 h). Receptor mRNA levels declined after the peak of the LH surge and were significantly lower by 2000 h. Pentobarbital treatment, which inhibits hypothalamic input and the LH surge, prevented the gonadotropin surge-associated increase in GnRH-R mRNA levels in E-primed OVX rats. Although GnRH-R mRNA levels did not change throughout the day of experiments in OVX unprimed rats, treatment with pentobarbital significantly reduced GnRH-R mRNA expression in these animals. P treatment of E-primed OVX rats had no significant effect on GnRH-R mRNA expression during the LH surge, but significantly reduced mRNA levels immediately after the LH surge (2000 h). Data from in vitro perifusion experiments using either metestrous or proestrous pituitary glands demonstrated that pulsatile GnRH up-regulates the expression of its own receptor mRNA at both estrous cycle stages. Based on these results, we conclude that enhanced GnRH-R mRNA expression observed on the day of proestrus is largely due to the actions of E, exerted indirectly via hypothalamic routes (presumably through enhanced GnRH secretion). Furthermore, preovulatory P secretion may account for the rapid decline in GnRH-R mRNA levels observed on the evening of proestrus.