FSH and its second messenger cAMP stimulate the transcription of human anti-Müllerian hormone in cultured granulosa cells

Mol Endocrinol. 2011 Apr;25(4):645-55. doi: 10.1210/me.2010-0297. Epub 2011 Feb 17.

Abstract

Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance, a member of the TGF-ß family, is responsible for the regression of Müllerian ducts in the male fetus. In females, AMH is synthesized by granulosa cells of preantral and small antral follicles, and production wanes at later stages of follicle maturation. Using RT-PCR in luteal granulosa cells in primary culture and reporter gene techniques in the KK1 granulosa cell line, we show that FSH and cAMP enhance AMH transcription, and LH has an additive effect. Gonadotropins and cAMP act through protein kinase A and p38 MAPK signaling pathways and involve the GATA binding factor-4 and steroidogenic factor-1 transcription factors, among others. The expression profile of AMH and the dynamics of serum AMH after gonadotropin stimulation have been interpreted as a down-regulating effect of FSH upon AMH production by granulosa cells. The specific effect of gonadotropins upon granulosa cells may be obscured in vivo by the effect of FSH upon follicular maturation and by the presence of other hormones and growth factors, acting individually or in concert.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Mullerian Hormone / genetics*
  • Cells, Cultured
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Female
  • Follicle Stimulating Hormone / metabolism*
  • GATA4 Transcription Factor / metabolism
  • Genes, Reporter
  • Gonadotropins / metabolism
  • Granulosa Cells / metabolism*
  • Humans
  • Luteinizing Hormone / metabolism
  • Mice
  • Ovarian Follicle / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroidogenic Factor 1 / metabolism
  • Transcription, Genetic*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • GATA4 Transcription Factor
  • Gata4 protein, mouse
  • Gonadotropins
  • Steroidogenic Factor 1
  • steroidogenic factor 1, mouse
  • Anti-Mullerian Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • p38 Mitogen-Activated Protein Kinases