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A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus
The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cro...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870887/ https://www.ncbi.nlm.nih.gov/pubmed/26963473 http://dx.doi.org/10.1210/en.2015-2032 |
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author | Simitsidellis, Ioannis Gibson, Douglas A. Cousins, Fiona L. Esnal-Zufiaurre, Arantza Saunders, Philippa T. K. |
author_facet | Simitsidellis, Ioannis Gibson, Douglas A. Cousins, Fiona L. Esnal-Zufiaurre, Arantza Saunders, Philippa T. K. |
author_sort | Simitsidellis, Ioannis |
collection | PubMed |
description | The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women. |
format | Online Article Text |
id | pubmed-4870887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-48708872016-05-25 A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus Simitsidellis, Ioannis Gibson, Douglas A. Cousins, Fiona L. Esnal-Zufiaurre, Arantza Saunders, Philippa T. K. Endocrinology Original Research The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women. Endocrine Society 2016-05 2016-03-10 /pmc/articles/PMC4870887/ /pubmed/26963473 http://dx.doi.org/10.1210/en.2015-2032 Text en https://creativecommons.org/licenses/by/4.0/ This article has been published under the terms of the Creative Commons Attribution License (CC-BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s). |
spellingShingle | Original Research Simitsidellis, Ioannis Gibson, Douglas A. Cousins, Fiona L. Esnal-Zufiaurre, Arantza Saunders, Philippa T. K. A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus |
title | A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus |
title_full | A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus |
title_fullStr | A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus |
title_full_unstemmed | A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus |
title_short | A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus |
title_sort | role for androgens in epithelial proliferation and formation of glands in the mouse uterus |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870887/ https://www.ncbi.nlm.nih.gov/pubmed/26963473 http://dx.doi.org/10.1210/en.2015-2032 |
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