Browsing by Subject "Estrogens"
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Item Antagonistic Roles of miR-199a-3p/miR-214 and the miR-200 Family in the Regulation of Uterine Contractility During Pregnancy and Labor(2014-02-03) Williams, Koriand'r; Hammer, Robert; Mendelson, Carole R.; Mahendroo, Mala; Olson, Eric N.Progesterone (P4) and estradiol-17β (E2) play critical and opposing roles in regulating myometrial quiescence and contractility during pregnancy and labor (Kamel et al., 2010). While these contrasting hormonal effects are likely mediated via differential regulation of inflammatory and contractile genes, the underlying mechanisms remain incompletely understood. Recently, we discovered that miR-200 family members, miR-200b and miR-429, and their target, transcription factor ZEB1, serve as P4/progesterone receptor (PR)-mediated regulators of uterine quiescence during pregnancy (Renthal et al., 2010). In the present study, we identified a novel role for another miR-200 family member, miR-200a, to enhance local metabolism of P4 in myometrium and, thus, decrease PR function during the progression towards labor (Williams et. al., 2012a). This occurs via miR-200a repression of signal transducer and activator of transcription (STAT)5b, a transcriptional repressor of the P4-metabolizing enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD). We observed that miR-200a expression increased and STAT5b expression coordinately decreased in myometrium of mice as they progressed to labor and in laboring myometrium from pregnant women. These changes were associated with a dramatic increase in expression and activity of 20α-HSD in laboring myometrium from mouse and human. In a progesterone-withdrawal mouse model of preterm labor, preterm labor was associated with increased miR-200a, decreased STAT5b and enhanced 20α-HSD expression. In other studies, we also found that levels of the clustered miRNAs, miR-199a-3p and miR-214, were significantly decreased in laboring myometrium of pregnant mice and humans and in a inflammatory mouse model of preterm labor, while the miR-199a-3p/miR-214 target, cyclooxygenase-2 (COX-2), a critical enzyme in synthesis of pro-inflammatory prostaglandins, was coordinately increased (Williams et al., 2012b). The physiological relevance of the labor-associated increase in miR-199a-3p/214 expression was highlighted by the finding that overexpression of miR-199a-3p and miR-214 in cultured human myometrial cells inhibited COX-2 protein and blocked TNF-α-induced myometrial cell contractility. Notably, estrogen and P4 treatment of ovariectomized mice have opposing effects on uterine miR-199a-3p/214 expression that were mediated by ZEB1. Whereas, P4 stimulated ZEB1 and upregulated miR-199a/214 expression in mouse and human myometrium (Renthal et al., 2010), estrogen had an opposing inhibitory effect. Notably, ZEB1/2 inhibit miR-200 family expression. Together, our findings point to the key pivotal roles of myometrial ZEB1 and its miRNA targets as a hormonally-controlled regulators of inflammatory and contractile gene expression in the pregnant uterus during term and preterm labor.Item Assessing Laboratory Values in Transgender Women Treated with Cross-Sex Hormone Therapy(2018-01-23) Jiao, Rhoda; SoRelle, Jeffrey A.; Gao, Emily; Veazey, Jonas; Frame, Ithiel J.; Gimpel, Nora; Patel, Khushbu; Pagels, PattiOBJECTIVE: Laboratory results are used to guide clinical decision making, and reference ranges are developed to describe the variation seen in healthy individuals so that pathologic values can be distinguished from normal physiologic values. For transgender individuals taking cross-sex hormone therapy, changes in physiology can be expected to accompany the masculinization or feminization induced by the treatment, but the effect of these changes on laboratory tests is not well defined and cannot be easily predicted. This study seeks to evaluate the response of common laboratory tests to hormone replacement therapy (HRT) in transgender women (male-to-female, MTF), comparing to natal male and female populations. METHODS: We conducted a retrospective chart review for MTF and FTM (female-to-male) patients before initiating HRT and MTF patients after receiving HRT for 6-24 months at transgender-specific clinics in an urban county hospital (Parkland Hospital, Dallas, TX) and a community clinic (Resource Center, Dallas, TX). We collected demographic information, medical history, and laboratory values for CBCs, complete metabolic panels, liver function tests, lipids, and hormone levels taken throughout their course of treatment. RESULTS: In one of the largest studies of laboratory values in transgender patients, patient charts of 120 transgender women were reviewed, with a median age of 27 years. After initiating HRT, MTF patients showed a significantly increased estrogen and decreased testosterone (p<0.0001). Changes in hematologic parameters included decreases in red blood cell count, hemoglobin, and hematocrit (p<0.0001) and an increase in platelets (p=0.0001). Changes in metabolic parameters include decreases in sodium, creatinine, and alkaline phosphatase (p<0.0001). CONCLUSION: Better understanding the extent of expected changes in laboratory values can enable clinicians to more accurately evaluate the effects of HRT and choose appropriate treatments for individuals in the transgender population.Item Estrogen and the brain(2003-04-10) Kirk, Lynne M.Item Estrogen susceptibility: are all women created equal?(2000-05-11) Radford, Nina ButwellItem Molecular Mechanisms and Functions of Estrogen Receptor Enhancers in Hormone-Dependent Gene Expression(2017-11-21) Murakami, Shino; Kim, Tae-Kyung; Kraus, W. Lee; Kliewer, Steven A.; Zhang, Chun-LiTranscription is a fundamental regulatory mechanism of biological processes in a range of physiological and pathological conditions. Transcription enhancers are DNA regulatory elements that regulate the expression of the target genes by accommodating transcription factor (TF) binding through sequence specificity. Estrogen receptor alpha (ERα) belongs to ligand-dependent nuclear receptor superfamily. Upon activation by estrogenic ligands, ERα binds to specific sites on chromatin, and assembles and activates enhancer complexes, which in turn lead to the transcription of target genes. Various molecular events have been associated with enhancer function, including coregulator recruitment, induction of enhancer-enriched histone modifications, nucleosome remodeling, enhancer-promoter chromatin interactions, and transcription activation at the enhancer, as well as the target gene promoter. However, we lack a clear understanding of the order of events, the specific roles of each coregulator and enhancer-enriched chromatin features, and the functional relationships among them. Using ERα in estrogen (E2)-regulated gene transcription as a model in combination with molecular and cellular biology, as well as genomic and computational approaches, my dissertation herein describes a series of studies elucidating the molecular mechanisms and functions of these evens that lead to ERα enhancer activation. Collectively, it demonstrates that (1) ERα enhancer assembly and activation is a dynamic process, (2) the temporally-defined recruitment and activation of key coregulators are required for successful activation of ERα enhancers, and (3) enhancer transcripts (eRNA) mark active enhancers. Lastly, I delineate the development of a new technology, single-cell Global Run-on Sequencing (scGRO-seq), to uncover the link between enhancer activity and target gene transcription at the single-cell level. Single-cell imaging and sequencing technologies have demonstrated the heterogeneous nature of gene expression and enhancer activity in a wide range of biological systems, including clonally-expanded populations of cultured cells. However, our understanding on the molecular basis of heterogeneous gene expression is limited because of a lack of technologies that allow us to simultaneously examine enhancer activity and target gene transcription at the single-cell level. scGRO-seq will overcome this problem by capturing active transcription at the enhancers, which is an indicative of enhancer activity, and at the target gene in the same cells.Item [News](1983-01-14) Williams, AnnItem Postmenopausal estrogen supplementation: a cardiologist's perspective(1993-09-02) Butwell, Nina BethItem [Southwestern News](2003-04-16) Shields, AmyItem [Southwestern News](2001-06-19) Shields, AmyItem [Southwestern News](1999-02-01) Manley, Jennifer HaighItem [Southwestern News](1997-07-10) Steeves, Susan A.Item Use of estrogens after the menopause(1980-07-10) Wilson, Jean D.Item [UT News](1986-10-17) Harrell, AnnItem [UT Southwestern Medical Center News](2009-03-12) Stafford, Erin PratherItem [UT Southwestern Medical Center News](2010-06-23) Shear, Kristen HollandItem [UT Southwestern Medical Center News](2011-05-05) Russell, RobinItem [UT Southwestern Medical Center News](2011-10-20) Bolles, DebbieItem [UT Southwestern Medical Center News](2009-06-29) Piloto, Connie; Thomason, Charise