GnRH Inhibits FSH-Induced Steroidogenenisis by Suppressing FSH Receptor Expression via USF2 Transcriptional Factor.

Abstract

It is known that GnRH inhibits FSH-induced ovarian steroidogenenisis in vitro, the molecular mechanism, however, is not clear. To investigate the signal pathway of GnRH action, the granulsa cells obtained from the ovaries of DES-treated immature rats were cultured for 48 hours in the presence or absence of FSH (100ng/ml) and GnRH (10-6M) with androstenediol (10-6M). The FSH-induced estrogen and progesterone production were significantly inhibited by GnRH, 1.47 and 10.2 fold decreases in the estrogen and progesterone content were respectively detected. The FSH-induced cell expression of StAR, 3beta-HSD, aromatase, cytochrome P450 and cyp11a1 were also significantly suppressed by GnRH. Further studies confirmed that the inhibitory action of GnRH on the FSH-induced steroidogenenisis was via AKT signaling pathway. To more closely look at the molecular mechanism of AKT signaling in biosynthesis of estrogen and progesterone, the rat granulosa cells were cultured in the presence or absence of FSH and GnRH with 12.5 uM LY294002 (AKT signaling inhibitor), the cell extract were analyzed for FSHR expression and its upstream stimulatory factor 2 (USF2) activation. The experiment showed that both FSH-induced FSHR expression and USF2 activation were significantly suppressed in the same extent by GnRH and also via AKT signal pathway. In conclusion, GnRH inhibiting FSH-induced steroidogenenisis in granulosa cells might be by suppressing FSH-induced FSHR expression via USF2 transcriptional factor. (poster)