Effect of the interaction of metformin and bone morphogenetic proteins on ovarian steroidogenesis by human granulosa cells

Nahoko Iwata, Toru Hasegawa, Shiho Fujita, Satoko Nagao, Yasuhiro Nakano, Takahiro Nada, Yuki Nishiyama, Takeshi Hosoya, Fumio Otsuka

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In the present study, we studied the effects of metformin and its interactions with the actions of bone morphogenetic proteins (BMPs) on ovarian steroidogenesis. It was revealed that metformin treatment enhanced progesterone production by human granulosa KGN cells and rat primary granulosa cells induced by forskolin and FSH, respectively. In human granulosa cells, it was found that metformin treatment suppressed phosphorylation of Smad1/5/9 activated by BMP-15 compared with that induced by other BMP ligands. Moreover, metformin treatment increased the expression of inhibitory Smad6, but not of that Smad7, in human granulosa cells, while metformin had no significant impact on the expression levels of BMP type-I and -II receptors. Thus, the mechanism by which metformin suppresses BMP-15-induced Smad1/5/9 phosphorylation is likely, at least in part, to be upregulation of inhibitory Smad6 expression in granulosa cells. The results suggest the existence of functional interaction between metformin and BMP signaling, in which metformin enhances progesterone production by downregulating endogenous BMP-15 activity in granulosa cells.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusAccepted/In press - Jan 1 2018
Externally publishedYes

Keywords

  • Bone morphogenetic protein (BMP)
  • Granulosa cells
  • Metformin
  • Smad and steroidogenesis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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