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脑源性神经营养因子通过激活 FSH 受体介导的信号通路促进人卵巢颗粒细胞瘤细胞的甾体生成和增殖。

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

机构信息

Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China.

Department of Medical Statistics, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, People's Republic of China.

出版信息

Sci Rep. 2017 Mar 15;7(1):180. doi: 10.1038/s41598-017-00203-x.

DOI:10.1038/s41598-017-00203-x
PMID:28282971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5428030/
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.

摘要

脑源性神经营养因子（BDNF）和促卵泡激素受体（FSHR）在卵巢颗粒细胞中表达，在调节卵泡生长和卵母细胞成熟中发挥重要作用。研究表明，BDNF 相关信号通路与 FSHR mRNA 表达在调节卵泡发育中有关，但具体机制尚不清楚。本研究发现，BDNF 可刺激雌二醇和孕酮的分泌，并促进 KGN 细胞（人卵巢颗粒样细胞瘤系）的增殖。BDNF 处理还增加了磷酸化和泛素化的 FSHR，并激活了 cAMP/PKA/CREB 信号通路。此外，siRNA 抑制 BDNF 的表达显著减少了雌二醇的分泌，并下调了 FSHR、芳香化酶和磷酸化 CREB；同时，FSH 处理部分缓解了 BDNF siRNA 对 KGN 细胞的作用。这些发现表明，BDNF 调节颗粒细胞的功能，其作用可能通过 FSHR 偶联的信号通路介导，影响芳香化酶介导的类固醇生成。这些结果为优化卵巢颗粒细胞功能提供了一个替代的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/25efbb8e73df/41598_2017_203_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/cf6b8f8a1682/41598_2017_203_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/244746109de7/41598_2017_203_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/5739dcc8b542/41598_2017_203_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/41a747dbdfc1/41598_2017_203_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/fc8f0193a1a9/41598_2017_203_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/c518674ff6af/41598_2017_203_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/c80bf9884341/41598_2017_203_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/94a2253c05e8/41598_2017_203_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/25efbb8e73df/41598_2017_203_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/cf6b8f8a1682/41598_2017_203_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/244746109de7/41598_2017_203_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/5739dcc8b542/41598_2017_203_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/41a747dbdfc1/41598_2017_203_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/fc8f0193a1a9/41598_2017_203_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/c518674ff6af/41598_2017_203_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/c80bf9884341/41598_2017_203_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/94a2253c05e8/41598_2017_203_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4f/5428030/25efbb8e73df/41598_2017_203_Fig9_HTML.jpg

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