Progesterone as a regulator of granulosa cell viability.
Progesterone as a regulator of granulosa cell viability.
复制标题
黄体酮作为颗粒细胞活力的调节剂。
DOI：
10.1016/s0960-0760(03)00192-4
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Peluso,JJ
中科院分区：
文献类型：
--
作者：
Peluso,JJ
孕激素（P4）阻止许多细胞，包括子宫，乳腺和卵巢细胞，进行凋亡。有趣的是，P4阻止卵巢颗粒细胞（GC）的凋亡，这些细胞不表达经典的核P4受体。本文综述了支持P4在颗粒细胞中的非基因组作用的数据。这些研究使用原代大鼠颗粒细胞和大鼠自发永生化颗粒细胞（SIGCs）进行。具体地，这些研究揭示了（1）3 H-P4特异性结合SIGC;（2）针对核P4受体（C-262）的配体结合结构域的抗体检测到60 kDa蛋白，其定位于质膜并结合P4;和（3）用C-262处理阻断P4维持颗粒细胞活力的能力。其他研究表明，蛋白激酶G（PKG）激活剂8-br-cGMP模拟物和PKG拮抗剂Rp-8-pcCPT-GMP和KT 5823减弱P4的作用。这些研究支持了60 kDa P4结合蛋白作为P4的膜受体的功能，其激活PKG依赖性机制来调节颗粒细胞存活的概念。
Progesterone (P4) prevents numerous cells, including uterine, mammary and ovarian cells, from undergoing apoptosis. Interestingly, P4 prevents apoptosis of ovarian granulosa cells (GCs), which do not express the classic nuclear P4 receptor. This review presents data that support a non-genomic action of P4 in granulosa cells. These studies were conducted using both primary rat granulosa cells and rat spontaneously immortalized granulosa cells (SIGCs). Specifically, these studies reveal that (1)3H -P4 specifically binds to SIGCs; (2) an antibody directed against the ligand binding domain of the nuclear P4 receptor (C-262) detects a 60kDa protein, which localizes to the plasma membrane and binds P4; and (3) treatment with C-262 blocks P4’s ability to maintain granulosa cell viability. Additional studies demonstrate that a protein kinase G (PKG) activator, 8-br-cGMP, mimics and PKG antagonists, Rp-8-pcCPT-GMP and KT5823, attenuate P4’s action. These studies support the concept that the 60kDa P4 binding protein functions as membrane receptor for P4 which activates a PKG-dependent mechanism to regulate granulosa cell survival.