title: Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis.
abstract: Follicular differentiation is a tightly regulated process involving various endocrine, autocrine, and paracrine factors. The biosynthesis of progesterone and estradiol in response to FSH involves the regulation of multiple steroidogenic enzymes, such as p450 cholesterol side-chain cleavage enzyme and aromatase. Here we demonstrated that prohibitin (PHB), a multifunctional protein, inhibits FSH-induced progesterone and estradiol secretion in rat granulosa cells. The mRNA abundances of cyp11a (coding p450 cholesterol side-chain cleavage enzyme) and cyp19 (coding aromatase) were also suppressed by PHB in a time-dependent manner. It is known that a novel adipokine chemerin suppresses FSH-induced steroidogenesis in granulosa cells. Chemerin up-regulates the content of PHB, and PHB knockdown attenuates the suppressive role of chemerin on steroidogenesis. In addition, inhibition of phosphatidylinositol 3-kinase/Akt pathway enhances the suppressive action of PHB, whereas expression of constitutively active Akt attenuates this response. These findings suggest that PHB is a novel negative regulator of FSH-induced steroidogenesis, and its action with chemerin may contribute to the dysregulation of steroidogenesis in the pathogenesis of polycystic ovarian syndrome.
authors.affiliation: Departments of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Arthur
authors.initials: A
authors.lastname: Leader
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang
mesh_terms: D054392:Adipokines / Q000502:physiology*; D000818:Animals; D018925:Chemokines; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D000091402:Prohibitins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: D054392:Adipokines; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C000717332:Phb protein, rat; D000091402:Prohibitins; C560738:Rarres2 protein, rat; D012097:Repressor Proteins; D005640:Follicle Stimulating Hormone; D002786:Cholesterol Side-Chain Cleavage Enzyme