Progesterone receptor membrane component 1 and its role in ovarian follicle growth.

Progesterone receptor membrane component 1 and its role in ovarian follicle growth.
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DOI:
10.3389/fnins.2013.00099
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发表时间:
2013
影响因子:
4.3
通讯作者:
Peluso JJ
Peluso JJ
中科院分区:
医学2区
文献类型:
--
作者:
Peluso JJ

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黄体酮(P4)在卵巢中合成,直接作用于发育中的卵泡颗粒细胞,抑制其有丝分裂和凋亡的速率。颗粒细胞不表达核孕激素受体(PGR),而表达孕激素受体膜组分-1 (PGRMC1)。PGRMC1结合P4并介导P4的作用,PGRMC1 siRNA研究证实了这一点。PGRMC1通过结合纤溶酶原激活物抑制剂1 rna结合蛋白,调控基因表达。具体来说,PGRMC1抑制一些促进细胞死亡的基因(即Bad、Caspase-3、Caspase-4)。P4部分通过抑制PGRMC1与Tcf/ left转录位点的结合来调节基因表达,从而降低Tcf/ left转录活性。由于Tcf/Lef转录位点位于启动有丝分裂和/或凋亡的基因(即c-jun和c-myc)的启动子内,P4- pgrmc1介导的Tcf/Lef调控基因的抑制可能解释了P4的作用。PGRMC1在多囊卵巢综合征、卵巢早衰和不孕症患者中的表达也发生改变。总的来说,这些观察结果支持PGRMC1在调节人类卵泡发育中的作用。
Progesterone (P4) is synthesized in the ovary and acts directly on granulosa cells of developing ovarian follicles to suppress their rate of mitosis and apoptosis. Granulosa cells do not express nuclear progesterone receptor (PGR) but rather progesterone receptor membrane component-1 (PGRMC1). PGRMC1 binds P4 and mediates P4's actions, as evidenced by PGRMC1 siRNA studies. PGRMC1 acts by binding plasminogen activator inhibitor 1 RNA-binding protein and regulating gene expression. Specifically, PGRMC1 suppresses some genes that promote cell death (i.e., Bad, Caspase-3, Caspase-4). P4 regulates gene expression in part by inhibiting PGRMC1 binding to Tcf/Lef transcription sites, thereby reducing Tcf/Lef transcriptional activity. Since Tcf/Lef transcription sites are located within the promoters of genes that initiate mitosis and/or apoptosis (i.e., c-jun and c-myc), P4-PGRMC1 mediated suppression of these Tcf/Lef regulated genes could account for P4's actions. PGRMC1 expression is also altered in women with polycystic ovarian syndrome, premature ovarian failure and infertility. Collectively, these observations support a role for PGRMC1 in regulating human ovarian follicle development.
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