UC Irvine

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