Inhibitory Roles of Prohibitin and Chemerin in FSH-Induced Rat Granulosa Cell Steroidogenesis

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 asp450cholesterol 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. (Endocrinology 154: 956-967, 2013)