Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells

Fadhillah, Shin Yoshioka, Ryo Nishimura, Yuki Yamamoto, Koji Kimura, Kiyoshi Okuda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Hypoxia has been suggested to enhance progesterone (P4) synthesis in luteinizing granulosa cells (GCs), but the mechanism is unclear. The present study was designed to test the hypothesis that the hypoxia-induced increase in P4 synthesis during luteinization in bovine GCs is mediated by hypoxia-inducible factor 1 (HIF-1). GCs obtained from small antral follicles were cultured with 2 µg/ml insulin in combination with 10 µM forskolin for 24 h as a model of luteinizing GCs. To examine the influence of HIF-1 on P4 synthesis, we determined the effect of changes in protein expression of the α-subunit of HIF-1 (HIF1A) on P4 production and on the expression levels of StAR, P450scc, and 3β-HSD. CoCl2 (100 µM), a hypoxia-mimicking chemical, increased HIF-1α protein expression in luteinizing GCs. After the upregulation of HIF-1α, we observed an increase in P4 production and in the gene and protein expression levels of StAR in CoCl2-treated luteinizing GCs. In contrast, CoCl2 did not affect the expression of either P450scc or 3β-HSD. Echinomycin, a small-molecule inhibitor of HIF-1’s DNA-binding activity, attenuated the effects of CoCl2 and of low oxygen tension (10% O2) on P4 production and StAR expression in luteinizing GCs. Overall, these findings suggest that HIF-1 is one of the factors that upregulate P4 in GCs during luteinization.

Original languageEnglish
Pages (from-to)75-85
Number of pages11
JournalJournal of Reproduction and Development
Volume63
Issue number1
DOIs
Publication statusPublished - 2017

Fingerprint

luteinization
granulosa cells
hypoxia
progesterone
synthesis
protein synthesis
forskolin
hypoxia-inducible factor 1
insulin
oxygen
gene expression

Keywords

  • Corpus luteum
  • Granulosa cell
  • Ovary
  • Progesterone

ASJC Scopus subject areas

  • Animal Science and Zoology

Cite this

Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells. / Fadhillah; Yoshioka, Shin; Nishimura, Ryo; Yamamoto, Yuki; Kimura, Koji; Okuda, Kiyoshi.

In: Journal of Reproduction and Development, Vol. 63, No. 1, 2017, p. 75-85.

Research output: Contribution to journalArticle

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