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

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-indu...

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Autores principales: FADHILLAH, YOSHIOKA, Shin, NISHIMURA, Ryo, YAMAMOTO, Yuki, KIMURA, Koji, OKUDA, Kiyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Society for Reproduction and Development 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320433/
https://www.ncbi.nlm.nih.gov/pubmed/27840375
http://dx.doi.org/10.1262/jrd.2016-068
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author FADHILLAH,
YOSHIOKA, Shin
NISHIMURA, Ryo
YAMAMOTO, Yuki
KIMURA, Koji
OKUDA, Kiyoshi
author_facet FADHILLAH,
YOSHIOKA, Shin
NISHIMURA, Ryo
YAMAMOTO, Yuki
KIMURA, Koji
OKUDA, Kiyoshi
author_sort FADHILLAH,
collection PubMed
description 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. CoCl(2) (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 CoCl(2)-treated luteinizing GCs. In contrast, CoCl(2) 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 CoCl(2) and of low oxygen tension (10% O(2)) 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.
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spelling pubmed-53204332017-02-27 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 J Reprod Dev Original Article 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. CoCl(2) (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 CoCl(2)-treated luteinizing GCs. In contrast, CoCl(2) 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 CoCl(2) and of low oxygen tension (10% O(2)) 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. The Society for Reproduction and Development 2016-11-11 2017-02 /pmc/articles/PMC5320433/ /pubmed/27840375 http://dx.doi.org/10.1262/jrd.2016-068 Text en ©2017 Society for Reproduction and Development This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: http://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Article
FADHILLAH,
YOSHIOKA, Shin
NISHIMURA, Ryo
YAMAMOTO, Yuki
KIMURA, Koji
OKUDA, Kiyoshi
Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells
title Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells
title_full Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells
title_fullStr Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells
title_full_unstemmed Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells
title_short Hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells
title_sort hypoxia-inducible factor 1 mediates hypoxia-enhanced synthesis of progesterone during luteinization of granulosa cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320433/
https://www.ncbi.nlm.nih.gov/pubmed/27840375
http://dx.doi.org/10.1262/jrd.2016-068
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