Involvement of BMP-15 in Glucocorticoid Actions on Ovarian Steroidogenesis by Rat Granulosa Cells

Abstract Glucocorticoid receptor (GR) are known to be expressed in the ovary and glucocorticoids shown exert direct effects on granulosa cell functions. In clinical setting, menstrual abnormality, amenorrhea hypermenorrhea can patients with glucocorticoid excess. On other hand, also used for treatment of PCOS hyperandrogenism. However, reproductive system have not been fully elucidated. present study, we investigated influence follicular steroidogenesis using primary culture rat cells, by focusing ovarian bone morphogenetic proteins (BMPs) acting as a luteinizing inhibitor. Granulosa cells isolated from female immature rats were treated follicle-stimulating hormone (FSH) presence dexamethasone (Dex) serum-free conditions. After Dex 48 h, changes estradiol (E2) progesterone (P4) production cAMP synthesis induced FSH treatments measured ELISA. Total RNAs FSH, BMPs extracted mRNA levels steroidogenetic factors enzymes, BMP receptors Id-1 quantified real-time RT-PCR. Phosphorylation Smad1/5/9 was evaluated Western blotting lysates or absence Dex. As result, it revealed that decreased FSH-induced E2 cells. accordance steroid results, suppressed P450arom expression well By contrast, augmented P4 concentration-dependent manner. found enhance basal P4-synthetic enzymes including P450scc 3βHSD. Of note, activated target gene transcription phosphorylation, particular, BMP-15 among various ligands BMP-2, -4, -6, -7, -9 -15. It increased ALK-6, type-I BMP-15, turn upregulated GR Given acts an inhibitor suppressing FSH-receptor actions, suggested is functionally linked enhancement endogenous leading negative feedback toward overproduction Collectively, elicit differential P4, which actions mutually enhanced