Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway

Abstract Brain-derived neurotrophic factor (BDNF) and FSH receptor (FSHR) are expressed in ovarian granulosa cells, and play important roles in regulating follicle growth and oocyte maturation. Studies have linked the BDNF-associated signaling pathway to FSHR mRNA expression in the regulation of fol...

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Autores principales:	Min Xie, Meiling Li, Ji Zhou, Xiaomeng Ding, Yidan Shao, Jun Jing, Yuxiu Liu, Bing Yao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb52747046fe4153848a1aa525c9212c
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spelling	oai:doaj.org-article:bb52747046fe4153848a1aa525c9212c2021-12-02T15:04:55ZBrain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway10.1038/s41598-017-00203-x2045-2322https://doaj.org/article/bb52747046fe4153848a1aa525c9212c2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00203-xhttps://doaj.org/toc/2045-2322Abstract Brain-derived neurotrophic factor (BDNF) and FSH receptor (FSHR) are expressed in ovarian granulosa cells, and play important roles in regulating follicle growth and oocyte maturation. Studies have linked the BDNF-associated signaling pathway to FSHR mRNA expression in the regulation of follicle development, but the mechanisms remain unknown. In the current study, we found that BDNF stimulated the secretion of estradiol and progesterone, and increased the proliferation of KGN cells (human granulosa-like tumor cell line). BDNF treatment also increased phosphorylated and ubiquitinated FSHR, and activated cAMP/PKA/CREB signaling pathway. Moreover, inhibition of BDNF expression by siRNA markedly reduced the estradiol secretion and down-regulated FSHR, aromatase and phosphorylated CREB; meanwhile, FSH treatment partly alleviated the effects of BDNF siRNA on KGN cells. These findings suggested that BDNF modulates graunlosa cell functions and the action probably mediated by FSHR-coupled signaling pathway, to affect aromatase-mediated steroidogenesis. These results provide an alternative target to optimize ovarian granulosa cell function.Min XieMeiling LiJi ZhouXiaomeng DingYidan ShaoJun JingYuxiu LiuBing YaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Min Xie Meiling Li Ji Zhou Xiaomeng Ding Yidan Shao Jun Jing Yuxiu Liu Bing Yao Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway
description	Abstract Brain-derived neurotrophic factor (BDNF) and FSH receptor (FSHR) are expressed in ovarian granulosa cells, and play important roles in regulating follicle growth and oocyte maturation. Studies have linked the BDNF-associated signaling pathway to FSHR mRNA expression in the regulation of follicle development, but the mechanisms remain unknown. In the current study, we found that BDNF stimulated the secretion of estradiol and progesterone, and increased the proliferation of KGN cells (human granulosa-like tumor cell line). BDNF treatment also increased phosphorylated and ubiquitinated FSHR, and activated cAMP/PKA/CREB signaling pathway. Moreover, inhibition of BDNF expression by siRNA markedly reduced the estradiol secretion and down-regulated FSHR, aromatase and phosphorylated CREB; meanwhile, FSH treatment partly alleviated the effects of BDNF siRNA on KGN cells. These findings suggested that BDNF modulates graunlosa cell functions and the action probably mediated by FSHR-coupled signaling pathway, to affect aromatase-mediated steroidogenesis. These results provide an alternative target to optimize ovarian granulosa cell function.
format	article
author	Min Xie Meiling Li Ji Zhou Xiaomeng Ding Yidan Shao Jun Jing Yuxiu Liu Bing Yao
author_facet	Min Xie Meiling Li Ji Zhou Xiaomeng Ding Yidan Shao Jun Jing Yuxiu Liu Bing Yao
author_sort	Min Xie
title	Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway
title_short	Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway
title_full	Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway
title_fullStr	Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway
title_full_unstemmed	Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway
title_sort	brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the fsh receptor-mediated signaling pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bb52747046fe4153848a1aa525c9212c
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Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway

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