Evidence for gonadotropin-releasing hormone receptor mRNA expression by estrogen in rat granulosa cells

The hormonal regulation of ovarian gonadotropin-releasing hormone (GnRH) re ceptor mRNA expression has been examined by in situ hybridization in hypoph ysectomized immature rats. In hypophysectomized rats, GnRH receptor mRNA ex pression is localized in the interstitial cells. After diethylstilbestrol t reatment, most follicles grow to form early antral follicles and express Gn RH receptor mRNA in the peripheral part of the granulosa layer, indicating that the expression in the growing follicles is estrogen-dependent. Only we ak or no expression of the receptor mRNA is detectable in the atretic folli cles of hypophysectomized rats, whereas very strong expression has been obs erved in the granulosa cells of atretic follicles of intact immature rats. Administration of testosterone or a GnRH agonist, both of which are atretic agents for ovarian follicles, to hypophysectomized rats markedly increases the apoptotic cell death of the granulosa cells but fails to induce GnRH r eceptor mRNA expression. The co-administration of these agents with diethyl stilbestrol causes the granulosa cells of atretic follicles to express the receptor mRNA very strongly, suggesting that this mRNA expression in the at retic follicles is also estrogen-dependent. On the other hand, expression o f the receptor mRNA in the ovarian interstitial cells is not affected by hy pophysectomy or hormone treatments. All of these results clearly indicate t hat estrogen is essential for the expression of ovarian GnRH receptor mRNA in the granulosa cells of atretic follicles and growing follicles, whereas the expression in the interstitial cells is estrogen-independent.