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Effect of FSH Receptor‐Binding Inhibitor‐8 on FSH ‐Mediated Granulosa Cell Signaling and Proliferation
Author(s) -
Navalakhe Rajshri M.,
Jagtap Dhanashree D.,
Nayak Sumeet U.,
Nandedkar Tarala D.,
Mahale Smita D.
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12149
Subject(s) - follicle stimulating hormone , hormone receptor , follicle stimulating hormone receptor , medicine , endocrinology , granulosa cell , growth hormone releasing hormone receptor , receptor , autocrine signalling , thyrotropin releasing hormone receptor , biology , paracrine signalling , ovarian follicle , hormone , chemistry , microbiology and biotechnology , luteinizing hormone , cancer , breast cancer
Follicle‐stimulating hormone is important for mammalian reproduction. It acts through specific receptors located on the plasma membrane of granulosa cells in ovaries and S ertoli cells in testes. The binding of follicle‐stimulating hormone to its receptor activates intracytoplasmic signaling pathways leading to steroidogenesis. These steroids in turn regulate the follicle‐stimulating hormone action from the anterior pituitary through exerting negative feedback effect. In addition to steroids, non‐steroidal factors secreted by the ovaries are believed to modulate follicle‐stimulating hormone action through autocrine/paracrine mode. One such low molecular weight peptide referred to as follicle‐stimulating hormone receptor‐binding inhibitor‐8 purified from human follicular fluid has been extensively studied. Follicle‐stimulating hormone receptor‐binding inhibitor‐8 has been shown to inhibit binding of follicle‐stimulating hormone to its receptor. The present article describes the effect of follicle‐stimulating hormone receptor‐binding inhibitor‐8 on follicle‐stimulating hormone‐induced signaling in rat granulosa cells. Follicle‐stimulating hormone receptor‐binding inhibitor‐8 inhibited the follicle‐stimulating hormone‐induced c AMP , and the effect was observed to be mediated through the protein kinase A . Further, an inhibitory effect of follicle‐stimulating hormone receptor‐binding inhibitor‐8 on the granulosa cell proliferation was evaluated using COV 434 cell line which is derived from the human granulosa cell tumor. The effect of the peptide on the cell cycle analysis showed an increase in apoptotic population and the arrest of G 1 phase. These findings suggest that follicle‐stimulating hormone receptor‐binding inhibitor‐8 acts as a follicle‐stimulating hormone antagonist and affects the follicle‐stimulating hormone‐mediated signaling and proliferation in the granulosa cells.