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      Endometrial progesterone resistance and PCOS

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          Abstract

          Polycystic ovary syndrome (PCOS) is a state of altered steroid hormone production and activity. Chronic estrogen exposure or lack of progesterone due to ovarian dysfunction can result in endometrial hyperplasia and carcinoma. A key contributor to our understanding of progesterone as a critical regulator for normal uterine function has been the elucidation of progesterone receptor (PR) expression, regulation, and signaling pathways. Several human studies indicate that PR-mediated signaling pathways in the nucleus are associated with progesterone resistance in women with PCOS. The aim of this review is to provide an overview of endometrial progesterone resistance in women with PCOS; to present the PR structure, its different isoforms, and their expression in the endometrium; to illustrate the possible regulation of PR and PR-mediated signaling in progesterone resistance in women with PCOS; and to discuss current clinical treatments for atypical endometrial hyperplasia and endometrial carcinoma in women with PCOS and accompanying progesterone resistance.

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          Polycystic Ovary Syndrome

          David A Ehrmann (2005)
          New England Journal of Medicine, 352(12), 1223-1236
          Article 0 comments Cited 402 times – based on 0 reviews     Review now
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            Estrogen receptors and human disease.

            Bonnie J. Deroo, Kenneth S. Korach (2006)
            Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.
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              Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

              Richard Burney, Said Talbi, Amy Hamilton … (2007)
              The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.
              Article 0 comments Cited 187 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Biomed Sci
                Journal ID (iso-abbrev): J. Biomed. Sci
                Title: Journal of Biomedical Science
                Publisher: BioMed Central
                ISSN (Print): 1021-7770
                ISSN (Electronic): 1423-0127
                Publication date Collection: 2014
                Publication date (Electronic): 9 January 2014
                Volume: 21
                Issue: 1
                Page: 2
                Affiliations
                [1 ]Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden
                [2 ]Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
                [3 ]Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Shanghai Medical College and Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institute of Brain Science, Fudan University, Shanghai 200032, China
                Article
                Publisher ID: 1423-0127-21-2
                DOI: 10.1186/1423-0127-21-2
                PMC ID: 3917599
                PubMed ID: 24405633
                SO-VID: daa32add-5bef-48db-8c2e-7c9896f14fbe
                Copyright © Copyright © 2014 Li et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 8 October 2013
                Date accepted : 6 January 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular medicine
                Keywords: pcos,endometrium,progesterone receptor isoforms,progesterone resistance
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: pcos, endometrium, progesterone receptor isoforms, progesterone resistance

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