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• W1776304226 endingPage "2466" @default.
• W1776304226 startingPage "2452" @default.
• W1776304226 abstract "Follicle stimulating hormone (FSH) plays a central role in growth and differentiation of ovarian follicles. A plethora of information exists on molecular aspects of FSH responses but little is known about the mechanisms involved in its cross-talk with insulin/IGF-1 pathways implicated in the coordination of energy homeostasis in preovulatory granulosa cells (GCs). In this study, we hypothesized that FSH may regulate IRS-2 expression and thereby maintain the energy balance in GCs. We demonstrate here that FSH specifically increases IRS-2 expression in human and rat GCs. FSH-stimulated IRS-2 expression was inhibited by actinomycin D or cycloheximide. Furthermore, FSH decreases IRS-2 mRNA degradation indicating post-transcriptional stabilization. Herein, we demonstrate a role of cAMP pathway in the activation of IRS-2 expression by FSH. Scan and activity analysis of IRS-2 promoter demonstrated that FSH regulates IRS-2 expression through SP1 binding sites. FSH stimulates SP1 translocation into nucleus and its binding to IRS-2 promoter. These results are corroborated by the fact that siRNA mediated knockdown of IRS-2 decreased the FSH-stimulated PI3K activity, p-Akt levels, GLUT4 translocation and glucose uptake. However, FSH was not able to increase IRS-2 expression in GCs from PCOS women undergoing IVF. Interestingly, IRS-2 mRNA expression was downregulated in GCs from the PCOS rat model. Taken together, our findings establish that FSH induces IRS-2 expression and thereby activates PI3K, Akt and glucose uptake. Crucially, our data confirms a molecular defect in FSH action in PCOS GCs which may cause deceleration of metabolism and follicular growth leading to infertility. These results lend support for a therapeutic potential of IRS-2 in the management of PCOS." @default.
• W1776304226 created "2016-06-24" @default.
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• W1776304226 date "2015-12-01" @default.
• W1776304226 modified "2023-10-04" @default.
• W1776304226 title "FSH stimulates IRS-2 expression in human granulosa cells through cAMP/SP1, an inoperative FSH action in PCOS patients" @default.
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• W1776304226 doi "https://doi.org/10.1016/j.cellsig.2015.09.011" @default.
• W1776304226 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26388164" @default.
• W1776304226 hasPublicationYear "2015" @default.
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