Follistatin inhibits the function of the oocyte-derived factor BMP-15

Biochem Biophys Res Commun. 2001 Dec 21;289(5):961-6. doi: 10.1006/bbrc.2001.6103.


Recent studies have highlighted the importance of a novel oocyte-derived growth factor, bone morphogenetic protein-15 (BMP-15) in the regulation of proliferation and differentiation of granulosa cells in the ovary. Namely, BMP-15 stimulates granulosa cell mitosis and inhibits follicle-stimulating hormone (FSH) receptor mRNA expression in granulosa cell, thereby playing a critical role in the elaborate mechanism controlling ovarian folliculogenesis. At present, however, nothing is known about molecules which may regulate the biological activity of BMP-15. Here we demonstrate evidence that follistatin can form an inactive complex with BMP-15, through which follistatin inhibits BMP-15 bioactivities. The binding of follistatin to BMP-15 was directly demonstrated by a surface plasmon resonance biosensor, and the ability of follistatin to inhibit BMP-15 functions was determined by established BMP-15 bioassays using primary rat granulosa cells. Specifically, follistatin attenuated BMP-15 stimulation of granulosa cell proliferation and reversed BMP-15 inhibition of FSH receptor mRNA expression leading to the suppression of FSH-induced progesterone synthesis. This is the first demonstration of the biochemical interaction and biological antagonism of follistatin and BMP-15, which may be involved in the complex yet well-controlled mechanism of the regulation of follicle growth and development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activins / pharmacology*
  • Activins / physiology
  • Animals
  • Bone Morphogenetic Protein 15
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cells, Cultured
  • Female
  • Follistatin
  • Gene Expression / drug effects
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects
  • Granulosa Cells / physiology
  • Growth Differentiation Factor 9
  • Growth Substances / physiology*
  • Intercellular Signaling Peptides and Proteins*
  • Kinetics
  • Oocytes / drug effects*
  • Oocytes / physiology*
  • Ovarian Follicle / physiology
  • Progesterone / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, FSH / genetics
  • Recombinant Proteins / pharmacology


  • Bmp15 protein, rat
  • Bone Morphogenetic Protein 15
  • Follistatin
  • Gdf9 protein, rat
  • Growth Differentiation Factor 9
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, FSH
  • Recombinant Proteins
  • Activins
  • Progesterone