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

Fumio Otsuka, R. Kelly Moore, Shun ichiro Iemura, Naoto Ueno, Shunichi Shimasaki

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)961-966
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume289
Issue number5
DOIs
Publication statusPublished - Dec 21 2001
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 15
Follistatin
Oocytes
Granulosa Cells
FSH Receptors
Bioactivity
Messenger RNA
Surface Plasmon Resonance
Bioassay
Cell proliferation
Follicle Stimulating Hormone
Surface plasmon resonance
Biosensing Techniques
Growth and Development
Mitosis
Biosensors
Biological Assay

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Follistatin inhibits the function of the oocyte-derived factor BMP-15. / Otsuka, Fumio; Moore, R. Kelly; Iemura, Shun ichiro; Ueno, Naoto; Shimasaki, Shunichi.

In: Biochemical and Biophysical Research Communications, Vol. 289, No. 5, 21.12.2001, p. 961-966.

Research output: Contribution to journalArticle

Otsuka, Fumio ; Moore, R. Kelly ; Iemura, Shun ichiro ; Ueno, Naoto ; Shimasaki, Shunichi. / Follistatin inhibits the function of the oocyte-derived factor BMP-15. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 289, No. 5. pp. 961-966.
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