In:
Endocrinology, The Endocrine Society, Vol. 153, No. 4 ( 2012-04-01), p. 1915-1924
Abstract:
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 17β-estradiol (E2) at a dose of 30 μg/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 E2 replacement treatment for 12 wk. E2 increased the expression of CRHR2 in cultured smooth muscle cells, which was blocked by estrogen receptor-β antagonist. Ucn significantly suppressed the phenylephrine-induced phospholipase Cβ3 activation, inositol 1,4,5-trisphosphate (IP3) production, and intracellular Ca2+ elevation. Ucn stimulated the expression of active GTP-bound Gαs 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 Gαs-cAMP-protein kinase A signaling, leading to down-regulation of the phospholipase Cβ-IP3-Ca2+ signaling pathway.
Type of Medium:
Online Resource
ISSN:
0013-7227
,
1945-7170
DOI:
10.1210/en.2011-1939
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2012
detail.hit.zdb_id:
2011695-0
