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Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation

Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs....

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Autores principales: Chowdhury, Indrajit, Thomas, Kelwyn, Zeleznik, Anthony, Thompson, Winston E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064770/
https://www.ncbi.nlm.nih.gov/pubmed/27044659
http://dx.doi.org/10.1530/JME-15-0278
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author Chowdhury, Indrajit
Thomas, Kelwyn
Zeleznik, Anthony
Thompson, Winston E
author_facet Chowdhury, Indrajit
Thomas, Kelwyn
Zeleznik, Anthony
Thompson, Winston E
author_sort Chowdhury, Indrajit
collection PubMed
description Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E(2)) and progesterone (P(4)). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E(2) and P(4) synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs.
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spelling pubmed-50647702016-10-17 Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation Chowdhury, Indrajit Thomas, Kelwyn Zeleznik, Anthony Thompson, Winston E J Mol Endocrinol Research Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E(2)) and progesterone (P(4)). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E(2) and P(4) synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs. Bioscientifica Ltd 2016-05-01 /pmc/articles/PMC5064770/ /pubmed/27044659 http://dx.doi.org/10.1530/JME-15-0278 Text en © 2016 The authors http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/)
spellingShingle Research
Chowdhury, Indrajit
Thomas, Kelwyn
Zeleznik, Anthony
Thompson, Winston E
Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation
title Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation
title_full Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation
title_fullStr Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation
title_full_unstemmed Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation
title_short Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation
title_sort prohibitin regulates the fsh signaling pathway in rat granulosa cell differentiation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064770/
https://www.ncbi.nlm.nih.gov/pubmed/27044659
http://dx.doi.org/10.1530/JME-15-0278
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