Estrogen Regulates Local Cysteine Metabolism in Mouse Myometrium
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REPRODUCTIVE BIOLOGY: ORIGINAL ARTICLE
Estrogen Regulates Local Cysteine Metabolism in Mouse Myometrium Damian D. Guerra 1 & Rachael Bok 2 & Kelsey Breen 2 & Vibhuti Vyas 2 & Hua Jiang 3 & Kenneth N. MacLean 3 & K. Joseph Hurt 2,4 Received: 18 May 2020 / Accepted: 2 August 2020 # Society for Reproductive Investigation 2020
Abstract Sulfur amino acid metabolism influences reproductive physiology, and transsulfuration in particular may be critical for normal cellular function. The sex hormone estrogen (E2) modulates gene expression and redox balance in some tissues by inducing the transsulfuration enzymes cystathionine β-synthase (CBS) and cystathionine γ-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 E2 reciprocally regulates myometrial CBS and CSE expression. In ovariectomized mice, exogenous E2 upregulates CBS and downregulates CSE levels. E2 promotes CBS mRNA and protein expression but attenuates CSE protein expression without affecting CSE mRNA. This pattern of E2-stimulated changes in transsulfuration enzyme expression is specific to the uterine smooth muscle. E2 does not change vaginal or cervical expression of CBS or CSE significantly, and E2 decreases expression of CSE in the liver without affecting CBS. E2 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 E2 states such as estrus and pregnancy. Keywords Biochemistry . Cystathionine . Gaso-transmitter . Nitric oxide . One-carbon metabolism . Taurine . Transsulfuration . Uterine smooth muscle Summary sentence: Estrogen upregulates cystathionine-β-synthase (CBS) and downregulates cystathionine-γ-lyase (CSE) and cysteinesulfinic acid decarboxylase (CSAD) in a myometrium-specific manner suggesting local regulation of uterine cysteine metabolism. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43032-020-00284-6) contains supplementary material, which is available to authorized users. * K. Joseph Hurt [email protected] 1
Department of Biology , University of Louisville , 2301 South 3rd Street, Louisville, Kentucky 40292, USA
2
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USA
3
Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USA
4
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Mai
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