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J Cell Physiol ; 234(6): 9264-9273, 2019 06.
Article in English | MEDLINE | ID: mdl-30317617

ABSTRACT

Endogenous hydrogen sulfide (H2 S), synthesized by cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), is a potent vasodilator that can be stimulated by estradiol-17ß (E 2 ß) in uterine artery (UA) smooth muscle (UASMC) in vivo; however, the underlying mechanisms are unknown. This study tested a hypothesis that E 2 ß stimulates H 2 S biosynthesis by upregulating CBS expression via specific estrogen receptor (ER). Treatment with E 2 ß stimulated time- and concentration- dependent CBS and CSE messenger RNA (mRNA) and protein expressions, and H 2 S production in cultured primary UASMC isolated from late pregnant ewes, which were blocked by ICI 182,780. Treatment with specific ERα or ERß agonist mimicked these E 2 ß-stimulated responses, which were blocked by specific ERα or ERß antagonist. Moreover, E 2 ß activated both CBS and CSE promoters and ICI 182,780 blocked the E 2 ß-stimulated responses. Thus, E 2 ß stimulates H 2 S production by upregulating CBS and CSE expression via specific ER-dependent transcription in UASMC in vitro.


Subject(s)
Cystathionine beta-Synthase/metabolism , Cystathionine gamma-Lyase/metabolism , Estradiol/pharmacology , Hydrogen Sulfide/metabolism , Myocytes, Smooth Muscle/metabolism , Receptors, Estrogen/metabolism , Transcription, Genetic/drug effects , Uterine Artery/cytology , Animals , Cells, Cultured , Cystathionine beta-Synthase/genetics , Cystathionine gamma-Lyase/genetics , Myocytes, Smooth Muscle/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sheep
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