Estrogen Regulates Local Cysteine Metabolism in Mouse Myometrium

Sulfur amino acid metabolism influences reproductive physiology, and transsulfuration in particular may be critical for normal cellular function. The sex hormone estrogen (E-2) modulates gene expression and redox balance in some tissues by inducing the transsulfuration enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). The role of sex hormones in sulfur amino acid metabolism by uterine smooth muscle is not known. Here, we show that CBS and CSE proteins increase in the mouse myometrium during estrus and diestrus, respectively, suggesting that E(2)reciprocally regulates myometrial CBS and CSE expression. In ovariectomized mice, exogenous E(2)upregulates CBS and downregulates CSE levels. E(2)promotes CBS mRNA and protein expression but attenuates CSE protein expression without affecting CSE mRNA. This pattern of E-2-stimulated changes in transsulfuration enzyme expression is specific to the uterine smooth muscle. E(2)does not change vaginal or cervical expression of CBS or CSE significantly, and E(2)decreases expression of CSE in the liver without affecting CBS. E(2)also downregulates myometrial cysteinesulfinic acid decarboxylase (CSAD) and decreases myometrial biochemical synthesis of the gaso-transmitter hydrogen sulfide (H2S). These findings suggest that myometrial sulfur amino acid metabolism may regulate uterine redox homeostasis, with implications for the source and metabolism of myometrial cysteine in high E(2)states such as estrus and pregnancy.

Automated summary

Sulfur amino acid metabolism plays a role in reproductive physiology, with estrogen influencing gene expression and redox balance by regulating transsulfuration enzymes. In the mouse myometrium, E(2) reciprocally regulates CBS and CSE expression during different phases of the estrous cycle. E(2) specifically affects transsulfuration enzyme expression in uterine smooth muscle, suggesting a potential role in regulating uterine redox homeostasis.