ICI 182,780 Attenuates Selective Upregulation of Uterine Artery Cystathionine β-Synthase Expression in Rat Pregnancy

被引:1
|
作者
Bai, Jin [1 ]
Li, Yao [2 ]
Yan, Guofeng [2 ]
Zhou, Jing [2 ]
Salmeron, Alejandra Garcia [1 ]
Fategbe, Olamide Tolulope [1 ]
Kumar, Sathish [3 ]
Chen, Xuejin [2 ]
Chen, Dong-Bao [1 ]
机构
[1] Univ Calif Irvine, Dept Obstet & Gynecol, Irvine, CA 92697 USA
[2] Shanghai Jiao Tong Univ, Dept Lab Anim Sci, Sch Med, 280 South Chongqing Rd, Shanghai 200025, Peoples R China
[3] Univ Wisconsin Madison, Dept Comparat Biosci, Madison, WI 53706 USA
基金
美国国家卫生研究院;
关键词
uterine artery; cystathionine beta-synthase; endogenous estrogens; estrogen receptors; pregnancy; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL VASODILATOR PRODUCTION; BLOOD-FLOW; SYSTEMIC ARTERIES; OVINE UTERINE; HYDROGEN-SULFIDE; ESTROGEN; OVARIAN; PREECLAMPSIA; ALPHA;
D O I
10.3390/ijms241814384
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Endogenous hydrogen sulfide (H2S) produced by cystathionine beta-synthase (CBS) and cystathionine-gamma lyase (CSE) has emerged as a novel uterine vasodilator contributing to pregnancy-associated increases in uterine blood flow, which safeguard pregnancy health. Uterine artery (UA) H2S production is stimulated via exogenous estrogen replacement and is associated with elevated endogenous estrogens during pregnancy through the selective upregulation of CBS without altering CSE. However, how endogenous estrogens regulate uterine artery CBS expression in pregnancy is unknown. This study was conducted to test a hypothesis that endogenous estrogens selectively stimulate UA CBS expression via specific estrogen receptors (ER). Treatment with E-2 beta (0.01 to 100 nM) stimulated CBS but not CSE mRNA in organ cultures of fresh UA rings from both NP and P (gestational day 20, GD20) rats, with greater responses to all doses of E-2 beta tested in P vs. NP UA. ER antagonist ICI 182,780 (ICI, 1 mu M) completely attenuated E-2 beta-stimulated CBS mRNA in both NP and P rat UA. Subcutaneous injection with ICI 182,780 (0.3 mg/rat) of GD19 P rats for 24 h significantly inhibited UA CBS but not mRNA expression, consistent with reduced endothelial and smooth muscle cell CBS (but not CSE) protein. ICI did not alter mesenteric and renal artery CBS and CSE mRNA. In addition, ICI decreased endothelial nitric oxide synthase mRNA in UA but not in mesenteric or renal arteries. Thus, pregnancy-augmented UA CBS/H2S production is mediated by the actions of endogenous estrogens via specific ER in pregnant rats.
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页数:12
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