Inhibin A inhibits follicle-stimulating hormone (FSH) action by suppressing its receptor expression in cultured rat granulosa cells

• Published in: Molecular and cellular endocrinology 2009-01, Vol.298 (1), p.48-56
• Main Authors: Lu, Cuiling, Yang, Wei, Chen, Min, Liu, Tao, Yang, Junling, Tan, Ping, Li, Lei, Hu, Xiaoqian, Fan, Cuihong, Hu, Zhaoyuan, Liu, Yixun
• Format: Article
• Language: English
• Subjects: Animals; Aromatase - genetics; Aromatase - metabolism; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme - genetics; Cholesterol Side-Chain Cleavage Enzyme - metabolism; Colforsin - pharmacology; DAX-1 Orphan Nuclear Receptor; DNA-Binding Proteins - physiology; Female; Follicle Stimulating Hormone - antagonists & inhibitors; Follicle Stimulating Hormone - metabolism; Follicle Stimulating Hormone - physiology; FSH; FSHR; Gene Expression - drug effects; Granulosa cells; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Inhibin A; Inhibins - pharmacology; Promoter Regions, Genetic - drug effects; Rats; Rats, Sprague-Dawley; Receptors, Androgen - physiology; Receptors, FSH - genetics; Receptors, FSH - metabolism; Receptors, Retinoic Acid - physiology; Repressor Proteins - physiology; Steroidogenic Factor 1 - physiology; Steroids - biosynthesis
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2008.09.039

Inhibin has long been considered as a suppresser of follicle-stimulating hormone (FSH) secretion from anterior pituitary through pituitary–gonad negative feedback to regulate follicle development. We demonstrated that addition of inhibin A could significantly suppress FSH-induced FSHR mRNA level in cultured rat granulosa cells (GCs) measured by real-time PCR. The inhibin A exerted its action mainly by inhibiting FSHR promoter activity. Furthermore, exogenous inhibin A could dramatically decrease FSH-induced P450arom and P450scc level and suppress progesterone and estradiol production in the cultured GCs, but it did not decrease forskolin-induced steroidogenesis, indicating that the inhibitory effect of inhibin A on FSH action may be upstream of cAMP signaling. Inhibin A was also capable of suppressing FSH-induced expression of steroidogenic factor 1 (SF-1) and androgen receptor, but stimulating DAX-1 expression in the culture. Our study has provided new evidence to show that inhibin A is capable of feedback antagonizing FSH action on GCs by reducing FSHR expression at ovarian level via a short feedback loop. Transcriptional factor receptors, such as SF-1, AR and DAX-1 were involved in this regulation.