Estradiol-17β stimulates H2S biosynthesis by ER-dependent CBS and CSE transcription in uterine artery smooth muscle cells in vitro

Endogenous hydrogen sulfide (H2S), synthesized by cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), is a potent vasodilator that can be stimulated by estradiol-17 beta (E-2 beta) in uterine artery (UA) smooth muscle (UASMC) in vivo; however, the underlying mechanisms are unknown. This study tested a hypothesis that E-2 beta stimulates H2S biosynthesis by upregulating CBS expression via specific estrogen receptor (ER). Treatment with E-2 beta stimulated time- and concentration- dependent CBS and CSE messenger RNA (mRNA) and protein expressions, and H2S production in cultured primary UASMC isolated from late pregnant ewes, which were blocked by ICI 182,780. Treatment with specific ER alpha or ER beta agonist mimicked these E-2 beta-stimulated responses, which were blocked by specific ER alpha or ER beta antagonist. Moreover, E-2 beta activated both CBS and CSE promoters and ICI 182,780 blocked the E-2 beta-stimulated responses. Thus, E-2 beta stimulates H2S production by upregulating CBS and CSE expression via specific ER-dependent transcription in UASMC in vitro.