期刊
ENDOCRINOLOGY
卷 153, 期 4, 页码 1915-1924出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/en.2011-1939
关键词
-
资金
- National Natural Science Foundation of China [31000516, 30800908]
- Science and Technology Commission of Shanghai Municipals [09XD1405600]
Urocortin (Ucn), a member of CRH family, has been implicated to be one of the endogenous regulators in the cardiovascular system and exerts its effects locally via an autocrine/paracrine fashion. Previous studies have shown the gender difference in CRH-induced vasodilation in human skin, which is related to the concentration of estrogens during the menstrual cycle. The aim of this study was to investigate whether estrogens modulate Ucn/CRH receptor type 2 (CRHR2) expression in vascular smooth muscle, thereby leading to vasodilation. We performed sham operation or bilateral ovariectomy (OVX) on female Sprague Dawley rats. OVX rats were sc administered 17 beta-estradiol (E-2) at a dose of 30 mu g/kg.d or with placebo for 12 wk. Primary smooth muscle cells of aorta were used for the in vitro study. It was found that the Ucn-induced vasodilation and CRHR2 expression were decreased in OVX rats and restored by E-2 replacement treatment for 12 wk. E-2 increased the expression of CRHR2 in cultured smooth muscle cells, which was blocked by estrogen receptor-beta antagonist. Ucn significantly suppressed the phenylephrine-induced phospholipase C beta 3 activation, inositol 1,4,5-trisphosphate (IP3) production, and intracellular Ca2+ elevation. Ucn stimulated the expression of active GTP-bound G alpha s protein and cAMP production. The suppressive effects of Ucn on phenylephrine-induced IP3 production and intracellular Ca2+ elevation were blocked by the inhibitors of adenylate cyclase and protein kinase A. Our results demonstrate that estrogen maintains the expression of CRHR2 in aorta smooth muscle, thereby enhancing vasodilator actions of Ucn. Ucn exerts its vasorelaxant effects via G alpha s-cAMP-protein kinase A signaling, leading to down-regulation of the phospholipase C beta-IP3-Ca2+ signaling pathway. (Endocrinology 153: 1915-1924, 2012)
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