Interaction of ovarian steroidogenesis and clock gene expression modulated by bone morphogenetic protein-7 in human granulosa cells

Satoko Nagao, Nahoko Iwata, Yoshiaki Soejima, Takaaki Takiguchi, Tamami Aokage, Yuka Kozato, Yasuhiro Nakano, Takahiro Nada, Toru Hasegawa, Fumio Otsuka

Research output: Contribution to journalArticle

Abstract

A functional link between clock gene expression and ovarian steroidogenesis was studied using human granulosa KGN cells. Similarities between changes in the mRNA and protein expression levels of Bmal1 and Clock and those of Per2 and Cry1 were found in KGN cells after treatment with forskolin. Among the interrelationships between the expression levels of clock and steroidogenic factors, Clock mRNA had a strongly positive correlation with P450arom and a negative correlation with 3βHSD. Knockdown of Clock gene by siRNA resulted in a significant reduction of estradiol production by inhibiting P450arom expression, while it induced a significant increase of progesterone production by upregulating 3βHSD in KGN cells treated with forskolin. Moreover, BMP-7 had an enhancing effect on the expression of Clock mRNA and protein in KGN cells. Thus, the expression levels of Clock, being upregulated by forskolin and BMP-7, were functionally linked to estradiol production and progesterone suppression by human granulosa cells.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalEndocrine journal
Volume66
Issue number2
DOIs
Publication statusPublished - 2019

Keywords

  • Bone morphogenetic protein (BMP)
  • Clock
  • Granulosa cells
  • Steroidogeneis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Nagao, S., Iwata, N., Soejima, Y., Takiguchi, T., Aokage, T., Kozato, Y., Nakano, Y., Nada, T., Hasegawa, T., & Otsuka, F. (2019). Interaction of ovarian steroidogenesis and clock gene expression modulated by bone morphogenetic protein-7 in human granulosa cells. Endocrine journal, 66(2), 157-164. https://doi.org/10.1507/endocrj.EJ18-0423