Androgen receptor and miRNA-126* axis controls follicle-stimulating hormone receptor expression in porcine ovarian granulosa cells

Abstract

Androgen, which acts via the androgen receptor (AR), plays crucial roles in mammalian ovarian function. Recent studies showed that androgen/AR signaling regulates follicle-stimulating hormone receptor (FSHR) expression in follicles; however, the detailed mechanism underlying this regulation remained unknown. Here, we demonstrate that AR and miR-126* cooperate to inhibit FSHR expression and function in pig follicular granulosa cells (pGCs). In pGCs, overexpression of AR decreased, whereas knockdown increased, FSHR mRNA and protein expression; however, neither manipulation affected FSHR promoter activity. Using a dualluciferase reporter assay, we found that the FSHR gene is a direct target of miR-126*, which inhibits FSHR expression and increases the rate of AR-induced apoptosis in pGCs. Collectively, our data show for the first time that the AR/miR-126* axis exerts synergetic effects in the regulation of FSHR expression and apoptosis in pGCs. Our findings thus define a novel pathway, AR/miR-126*/FSHR, that regulates mammalian GC functions.Reproduction (2016) 152 161-169

Integrated Analysis of miRNA-mRNA Interaction Network in Porcine Granulosa Cells Undergoing Oxidative Stress

“…Apart from these well-known miRNAs, multiple newly identified OS-induced DEmiRNAs may also play vital roles in ovaries. miR-126 has been shown to induce GC apoptosis by directly targeting FSHR in pigs [64]. miR-142 regulates the proliferation and apoptosis of human GC by inhibiting TGFBR1 [65].…”

The Role of microRNAs in Ovarian Granulosa Cells in Health and Disease

“…The FSHR gene is a direct target of miR-126 * , which inhibits FSHR expression and increases the rate of AR-induced apoptosis. Therefore, AR and miR-126 * may cooperate to inhibit FSHR expression and induce apoptosis in GC (55). As GCs differentiate, they also express the luteinizing hormone/chorionic gonadotropin receptor (LHCGR).…”

Expression and localisation of FSHR, GHR and LHR in different tissues and reproductive organs of female yaks

“…Follicle stimulating hormone receptor (FSHR) and growth hormone receptor (GHR) are proteins synthesised and secreted by the pituitary gland, which play important roles in the maturation of follicles. Recent study showed that the AR/miR-126* axis exerts synergetic effects to regulate FSHR expression and apoptosis in pGCs [4]. Studies indicated that profiling of FSHR negative allosteric modulators on LH/CGR reveals biased antagonism with implications in steroidogenesis [2].…”