Progesterone together with estrogen attenuates homologous upregulation of gonadotropin-releasing hormone receptor mRNA in primary cultured rat pituitary cells (vol 13, pg 379, 2000)

In a previous study, we clearly demonstrated that an application of gonadot ropin-releasing hormone (GnRH) to cultured rat pituitary cells increased th e expression of GnRH receptor (GnRH-R) mRNA through transcriptional activat ion of GnRH-R gene rather than suppression of the turnover rate of GnRH-R m RNA. Along with GnRH, gonadal steroids seem to be an important regulator fo r GnRH-R expression in the pituitary gland. Recent in vivo studies reported that an application of gonadal steroids to gonadectomized animals modulate d GnRH-R mRNA expression in the pituitary gland. However, it has not been c learly understood whether steroids may act directly at the pituitary or ind irectly via modulation of hypothalamic GnRH release. Therefore, we assessed the effects of estrogen and progesterone on GnRH-R mRNA expression in prim ary cultured female rat pituitary cells. Neither estradiol nor progesterone modulates the basal expression of GnRH-R mRNA in primary cultured pituitar y cells. When cultured pituitary cells were exposed to different doses of e stradiol in combination with GnRH (0.2 nM), the GnRH-stimulated increment o f GnRH-R mRNA expression was not significantly changed by estradiol at any given doses. However, when different doses of progesterone were added to pr imary cultured pituitary cells in combination with GnRH (0.2 nM), GnRH-indu ced increases in GnRH-R mRNA levels were reduced in a dose-related manner, showing a significant reduction at 100 nM progesterone. Furthermore, the ad dition of estradiol reinforced the suppressive effect of progesterone on th e homologous upregulation of GnRH-R mRNA expression. Collectively, our resu lts clearly demonstrated that progesterone directly attenuates the homologo us upregulation of GnRH-R mRNA expression at the pituitary level, and that estradiol potentiates the effect of progesterone.