Antimüllerian hormone regulates stem cell factor expression in human granulosa cells

Fertil Steril. 2014 Dec;102(6):1742-50.e1. doi: 10.1016/j.fertnstert.2014.08.012. Epub 2014 Sep 17.


Objective: To determine whether there is a correlation between antimüllerian hormone (AMH) and stem cell factor (SCF) in serum, follicular fluid (FF), and granulosa cells (GCs), and to investigate a possible regulatory mechanism of AMH on SCF in human granulosa cells.

Design: Prospective clinical and experimental study.

Setting: Academic center.

Patient(s): 163 women undergoing IVF.

Intervention(s): Serum, FF, and GCs obtained in all women, primary cultures of human GCs.

Main outcome measure(s): AMH and SCF were analyzed in serum, FF, and GCs, using enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction, and immunoblotting.

Result(s): There was a significant negative correlation between AMH and SCF protein level in FF, and in the mRNA expression of AMH and SCF in GCs. Conversely, there was no correlation between AMH and SCF levels in serum. In primary cultures of human GCs, SCF was down-regulated by treatment with recombinant human AMH and was increased by cyclic adenosine 3':5' monophosphate (cAMP) in a dose-dependent manner. A protein kinase A (PKA) inhibitor (H89) significantly reversed the effects of recombinant human AMH and cAMP on SCF mRNA and protein expression.

Conclusion(s): This is the first report on a modulatory role for AMH as an ovarian/follicular autocrine/paracrine factor controlling SCF expression via the cAMP/PKA pathway.

Keywords: Antimüllerian hormone; cAMP/PKA pathway; granulosa cells; stem cell factor.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood
  • Anti-Mullerian Hormone / physiology*
  • Cells, Cultured
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Down-Regulation / drug effects
  • Female
  • Fertilization in Vitro
  • Follicular Fluid / metabolism
  • Granulosa Cells / metabolism*
  • Humans
  • Isoquinolines / pharmacology
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / physiology
  • Prospective Studies
  • RNA, Messenger / metabolism
  • Stem Cell Factor / biosynthesis*
  • Stem Cell Factor / blood
  • Sulfonamides / pharmacology


  • Isoquinolines
  • RNA, Messenger
  • Stem Cell Factor
  • Sulfonamides
  • Anti-Mullerian Hormone
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide