期刊
JOURNAL OF NEUROSCIENCE
卷 30, 期 39, 页码 12950-12957出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1158-10.2010
关键词
-
资金
- National Institutes of Health (NIH) [HD42635, HD001281, HD00849-23]
- Bayer HealthCare Pharmaceuticals
In hypothalamic astrocytes obtained from adult female rats, estradiol rapidly increased free cytoplasmic calcium concentrations ([Ca2+](i)) that facilitate progesterone synthesis. The present study demonstrated that estradiol (1 nM) significantly and maximally stimulated progesterone synthesis within 5 min, supporting a rapid, nongenomic mechanism. The group I metabotropic glutamate receptor (mGluR1a) antagonist LY 367385 [(S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid] attenuated both the estradiol-induced [Ca2+](i) release and progesterone synthesis. To investigate membrane-associated estrogen receptors (mERs), agonists for ER alpha, ER beta, STX-activated protein, and GPR30 were compared. The selective ER alpha agonist propylpyrazole triole (PPT) and STX most closely mimicked the estradiol-induced [Ca2+](i) responses, where PPT was more potent but less efficacious than STX. Only high doses (100 nM) of selective ER beta agonist diarylpropionitrile (DPN) and GPR30 agonist G-1 induced estradiol-like [Ca2+](i) responses. With the exception of DPN (even at 100 nM), all agonists stimulated progesterone synthesis. The PPT- and STX-induced [Ca2+](i) release and progesterone synthesis were blocked by LY 367385. While the G-1-stimulated [Ca2+](i) release was blocked by LY 367385, progesterone synthesis was not. Since GPR30 was detected intracellularly but not in the membrane, we interpreted these results to suggest that G-1 could activate mGluR1a on the membrane and GPR30 on the smooth endoplasmic reticulum to release intracellular calcium. Although STX and G-1 maximally stimulated [Ca2+](i) release in astrocytes from estrogen receptor-alpha knock-out (ERKO) mice, estradiol in vivo did not stimulate progesterone synthesis in the ERKO mice. Together, these results indicate that mER alpha is mainly responsible for the rapid, membrane-initiated estradiol-signaling that leads to progesterone synthesis in hypothalamic astrocytes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据