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

Mol Cell Endocrinol. 2009 Jan 27;298(1-2):48-56. doi: 10.1016/j.mce.2008.09.039. Epub 2008 Oct 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Gene Expression / drug effects
  • Granulosa Cells / drug effects*
  • Granulosa Cells / metabolism
  • 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

Substances

  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • Nr0b1 protein, rat
  • Receptors, Androgen
  • Receptors, FSH
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Steroidogenic Factor 1
  • Steroids
  • inhibin A
  • Colforsin
  • Inhibins
  • Follicle Stimulating Hormone
  • Aromatase
  • Cholesterol Side-Chain Cleavage Enzyme