Regulatory role of BMP-9 in steroidogenesis by rat ovarian granulosa cells

Takeshi Hosoya, Fumio Otsuka, Eri Nakamura, Tomohiro Terasaka, Kenichi Inagaki, Naoko Tsukamoto-Yamauchi, Takayuki Hara, Kishio Toma, Motoshi Komatsubara, Hirofumi Makino

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

BMPs expressed in the ovary differentially regulate steroidogenesis by granulosa cells. BMP-9, a circulating BMP, is associated with cell proliferation, apoptosis and differentiation in various tissues. However, the effects of BMP-9 on ovarian function have yet to be elucidated. Here we investigated BMP-9 actions on steroidogenesis using rat primary granulosa cells. BMP-9 potently suppressed FSH-induced progesterone production, whereas it did not affect FSH-induced estradiol production by granulosa cells. The effects of BMP-9 on FSH-induced steroidogenesis were not influenced by the presence of oocytes. FSH-induced cAMP synthesis and FSH-induced mRNA expression of steroidogenic factors, including StAR, P450scc, 3βHSD2 and FSHR, were suppressed by treatment with BMP-9. BMP-9 mRNA expression was detected in granulosa cells but not in oocytes. BMP-9 readily activated Smad1/5/8 phosphorylation and Id-1 transcription in granulosa cells. Analysis using ALK inhibitors indicated that BMP-9 actions were mediated via type-I receptors other than ALK-2, -3 and -6. Furthermore, experiments using extracellular domains (ECDs) for BMP type-I and -II receptor constructs revealed that the effects of BMP-9 were reversed by ECDs for ALK-1 and BMPRII. Thus, the functional receptors for BMP-9 in granulosa cells were most likely to be the complex of ALK-1 and BMPRII. Collectively, the results of the present study showed that BMP-9 can affect luteinization and that there are two possible sources of BMP-9, serum and granulosa cells in the ovary.

Original languageEnglish
Pages (from-to)85-91
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume147
DOIs
Publication statusPublished - Mar 2015

Keywords

  • Bone morphogenetic protein (BMP)
  • Follicle-stimulating hormone (FSH)
  • Granulosa cells
  • Oocyte
  • Steroidogenesis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulatory role of BMP-9 in steroidogenesis by rat ovarian granulosa cells'. Together they form a unique fingerprint.

  • Cite this