Molecular regulation of LHCGR expression by miR-122 during follicle growth in the rat ovary

• Published in: Molecular and cellular endocrinology 2017-02, Vol.442, p.81-89
• Main Authors: Menon, Bindu, Gulappa, Thippeswamy, Menon, K.M.J.
• Format: Article
• Language: English
• Subjects: Animals; Estradiol; Estradiol - metabolism; Female; Follicle stimulating hormone; Follicle Stimulating Hormone - metabolism; Granulosa Cells - metabolism; Luteinizing hormone receptor; microRNA; MicroRNAs - metabolism; miR-122; mRNA binding protein; Ovarian Follicle - metabolism; Ovary - metabolism; Progesterone - metabolism; Rats; Receptors, LH - metabolism; RNA, Messenger - metabolism; Up-Regulation - physiology
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2016.12.002

We have previously reported that LHCGR expression in the ovary is regulated through a post-transcriptional mechanism involving an mRNA binding protein designated as LRBP, which is regulated, at least in part, by a non-coding RNA, miR-122. Our present study examined the regulatory role of miR-122 in FSH-induced LHCGR expression during follicle development. Treatment of rat granulosa cells concurrently with FSH and 17β estradiol showed, as expected, a time-dependent increase in LHCGR mRNA levels as well as hCG-induced progesterone production. However, miR-122 expression was decreased during the early time periods, which preceded the increased expression of LHCGR mRNA. The role of miR-122 in FSH-induced LHCGR mRNA expression was then examined by overexpressing miR-122 prior to FSH stimulation by infecting granulosa cells with an adenoviral vector containing a miR-122 insert (AdmiR-122). Pretreatment with AdmiR-122 resulted in complete abrogation of FSH- mediated upregulation of LHCGR. AdmiR-122 also blocked FSH-induced decrease in LRBP expression and increased the binding of LHCGR mRNA to LRBP. Based on these results, we conclude that miR-122 plays a regulatory role in LHCGR expression by modulating LRBP levels during FSH-induced follicle growth. •LH receptor (LHCGR) is regulated by the microRNA, miR-122 during follicle development.•miR-122 is downregulated during FSH-induced LHCGR upregulation in rat granulosa cells.•miR-122 overexpression inhibits FSH-induced LHCGR upregulation by increasing the expression and binding activity of LRBP.