The involvement of hypoxia-inducible factor 1α (HIF1α)-stabilising factors in steroidogenic acute regulatory (STAR) protein-dependent steroidogenesis in murine KK1 granulosa cells
Autor: | Tina Gysin, Mariusz P. Kowalewski |
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Rok vydání: | 2021 |
Předmět: |
endocrine system
Granulosa Cells Ovary Hypoxia-Inducible Factor 1 alpha Subunit Phosphoproteins Cell Line Mixed Function Oxygenases Mice Endocrinology Reproductive Medicine Von Hippel-Lindau Tumor Suppressor Protein Genetics Animals Female Animal Science and Zoology Hypoxia Molecular Biology Signal Transduction Developmental Biology Biotechnology |
Zdroj: | Reproduction, Fertility and Development. 33:865-880 |
ISSN: | 1448-5990 1031-3613 |
DOI: | 10.1071/rd21170 |
Popis: | As a component of hypoxia-inducible factor 1 (HIF1)-complexes, HIF1α regulates the expression of steroidogenic acute regulatory (STAR) protein in granulosa cells. However, severe hypoxia or exaggeratedly expressed HIF1α have detrimental effects. HIF1α is regulated by factor inhibiting HIF (FIH), prolyl hydroxylases (PHD1, 2, 3) and von Hippel-Lindau (VHL) suppressor protein. In this study, the expression of FIH, PHD1, 2, 3 and VHL was investigated in murine ovaries and immortalised KK1 granulosa cells. We found FIH, VHL and PHD2 transcripts predominantly in growing tertiary follicles. Functional aspects were assessed in KK1 cells exposed to decreasing O2 (20%, 10%, 1%), by determining HIF1α, FIH, VHL, PHD1–3 and STAR expression. The main findings indicated gradually increasing PHD2 under lowered O2. Functional blocking of PHDs revealed biphasic effects on STAR expression; concomitantly with increasing HIF1α, STAR expression, which was initially induced, decreased significantly when HIF1α was strongly stabilised. Finally, PHD2 in particular might act as a specific regulator of HIF1α and, thereby, of STAR availability in granulosa cells. |
Databáze: | OpenAIRE |
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