PMID- 32820455 OWN - NLM STAT- MEDLINE DCOM- 20211123 LR - 20240226 IS - 1933-7205 (Electronic) IS - 1933-7191 (Linking) VI - 28 IP - 1 DP - 2021 Jan TI - Estrogen Regulates Local Cysteine Metabolism in Mouse Myometrium. PG - 79-90 LID - 10.1007/s43032-020-00284-6 [doi] AB - 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 (H(2)S). 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. FAU - Guerra, Damian D AU - Guerra DD AD - Department of Biology , University of Louisville , 2301 South 3rd Street, Louisville, Kentucky, 40292, USA. FAU - Bok, Rachael AU - Bok R AD - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO, 80045, USA. FAU - Breen, Kelsey AU - Breen K AD - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO, 80045, USA. FAU - Vyas, Vibhuti AU - Vyas V AD - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO, 80045, USA. FAU - Jiang, Hua AU - Jiang H AD - Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO, 80045, USA. FAU - MacLean, Kenneth N AU - MacLean KN AD - Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO, 80045, USA. FAU - Hurt, K Joseph AU - Hurt KJ AUID- ORCID: 0000-0001-6906-350X AD - Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO, 80045, USA. k.joseph.hurt@cuanschutz.edu. AD - Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, 12700 East 19th Avenue, Mail Stop 8613, Aurora, CO, 80045, USA. k.joseph.hurt@cuanschutz.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200820 PL - United States TA - Reprod Sci JT - Reproductive sciences (Thousand Oaks, Calif.) JID - 101291249 RN - 1EQV5MLY3D (Taurine) RN - 4G7DS2Q64Y (Progesterone) RN - 4TI98Z838E (Estradiol) RN - EC 4.2.1.22 (Cystathionine beta-Synthase) RN - EC 4.4.1.1 (Cystathionine gamma-Lyase) RN - K848JZ4886 (Cysteine) SB - IM MH - Animals MH - Cells, Cultured MH - Cystathionine beta-Synthase/genetics/metabolism MH - Cystathionine gamma-Lyase/genetics/metabolism MH - Cysteine/*metabolism MH - Estradiol/*pharmacology MH - Female MH - Humans MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myocytes, Smooth Muscle/*drug effects/metabolism MH - Myometrium/*drug effects/metabolism MH - Ovariectomy MH - Progesterone/pharmacology MH - Taurine/metabolism MH - Mice OTO - NOTNLM OT - Biochemistry OT - Cystathionine OT - Gaso-transmitter OT - Nitric oxide OT - One-carbon metabolism OT - Taurine OT - Transsulfuration OT - Uterine smooth muscle EDAT- 2020/08/21 06:00 MHDA- 2021/11/24 06:00 CRDT- 2020/08/22 06:00 PHST- 2020/05/18 00:00 [received] PHST- 2020/08/02 00:00 [accepted] PHST- 2020/08/21 06:00 [pubmed] PHST- 2021/11/24 06:00 [medline] PHST- 2020/08/22 06:00 [entrez] AID - 10.1007/s43032-020-00284-6 [pii] AID - 10.1007/s43032-020-00284-6 [doi] PST - ppublish SO - Reprod Sci. 2021 Jan;28(1):79-90. doi: 10.1007/s43032-020-00284-6. Epub 2020 Aug 20.