Role of ERα in Mediating Female Uterine Transcriptional Responses to IGF1
| العنوان: | Role of ERα in Mediating Female Uterine Transcriptional Responses to IGF1 |
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| المؤلفون: | Yukitomo Arao, Sydney L. Lierz, Sara A. Grimm, Wipawee Winuthayanon, Lauren J. Donoghue, J. Tyler Ramsey, Katherine J. Hamilton, Sylvia C. Hewitt, Kenneth S. Korach |
| المصدر: | Endocrinology |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, endocrine system, medicine.drug_class, Uterus, Biology, 03 medical and health sciences, Mice, Random Allocation, Endocrinology, Internal medicine, Progesterone receptor, medicine, Animals, Research Resource, Insulin-Like Growth Factor I, Receptor, Regulation of gene expression, Mice, Knockout, Genomics - Bioinformatics, Estrogen Receptor alpha, Estrogens, 3. Good health, Chromatin, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Nuclear receptor, Gene Expression Regulation, Estrogen, Female, Estrogen receptor alpha, hormones, hormone substitutes, and hormone antagonists |
| الوصف: | Estrogen (E2) signaling through its nuclear receptor, E2 receptor α (ERα) increases insulinlike growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor. Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs growth responses, we assessed the IGF1 transcriptional responses in PgrCre+Esr1f/f (called ERαUtcKO) mice, which selectively lack ERα in progesterone receptor (PGR) expressing cells, including all uterine cells, while maintaining ERα expression in other tissues and cells that do not express Pgr. Additionally, we profiled IGF1-induced ERα binding sites in uterine chromatin using chromatin immunoprecipitation sequencing. Herein, we explore the transcriptional and molecular signaling that underlies our findings to refine our understanding of uterine IGF1 signaling and identify ERα-mediated and ERα-independent uterine transcriptional responses. Defining these mechanisms in vivo in whole tissue and animal contexts provides details of nuclear receptor mediated mechanisms that impact biological systems and have potential applicability to reproductive processes of humans, livestock and wildlife. After treatment with IGF1, we compared transcriptional profiles of wild-type and ERα null tissues to ERα ChIP-seq data to find ER-α–independent and ER-α–dependent uterine responses to IGF1. |
| تدمد: | 1945-7170 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f4faa1a484aa0ac1c8f6509b8332917 https://pubmed.ncbi.nlm.nih.gov/28586424 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5f4faa1a484aa0ac1c8f6509b8332917 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457170 |
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