The role of hypoxia and HIF1α in the regulation of STAR-mediated steroidogenesis in granulosa cells. (5th February 2015)

• Record Type: Journal Article
• Authors: Kowalewski, Mariusz Pawel; Gram, Aykut; Boos, Alois
• Is Part Of: Molecular and cellular endocrinology. Volume 401(2015)
• Page Start: 35
• Page End: 44
• Publication Date: 2015-02-05
• Subjects: HIF1α -- Steroidogenesis -- STAR -- KK1 granulosa cells; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2014.11.023
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: Reduced O2 content was used to check the impact of hypoxia and HIF1α in STAR-mediated steroidogenesis in granulosa cell line. Severe hypoxia (1% and 5% O2) decreases basal and dbcAMP-stimulated, STAR-mediated progesterone synthesis. Partial hypoxia (10% O2) increases STAR expression and steroidogenesis in dbcAMP-treated cells. HIF1α binds to proximal Star -promoter. HIF1α positively regulates basal and hypoxia-induced STAR expression. Abstract: The adaptive responses to hypoxia are mediated by hypoxia-inducible factor 1 alpha (HIF1α). Its role, however, in regulating steroidogenesis remains poorly understood. We examined the role of hypoxia and HIF1α in regulating steroid acute regulatory protein (STAR) expression and steroidogenesis in immortalized (KK1) mouse granulosa cells under progressively lowering O2 concentrations (20%, 15%, 10%, 5%, 1%). Basal and dbcAMP-stimulated progesterone synthesis was decreased under severe hypoxia (1% and 5% O2 ). The partial hypoxia revealed opposing effects, with a significant increase in steroidogenic response at 10% O2 in dbcAMP-treated cells: Star -promoter activity, mRNA and protein expression were increased. The hypoxia-stimulated STAR expression was PKA-dependent. Binding of HIF1α to the Star -promoter was potentiated under partial hypoxia. Inhibition of the transcriptional activity or expression of HIF1α suppressed STAR-expression. HIF1α appears to be a positive regulator of basal and stimulated STAR-expression, which under partial hypoxia is capable of increasing the steroidogenic capacity of granulosa cells.