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The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair
After menstruation, the endometrium has a remarkable capacity for repair, but the factors involved remain undefined. We hypothesize adrenomedullin (AM) plays a role in this process. Premenstrually progesterone levels decline, stimulating prostaglandin (PG) synthesis, vasoconstriction, and hypoxia. T...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192419/ https://www.ncbi.nlm.nih.gov/pubmed/21558311 http://dx.doi.org/10.1210/en.2010-1256 |
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author | Maybin, Jacqueline A. Battersby, Sharon Hirani, Nikhil Nikitenko, Leonid L. Critchley, Hilary O. D. Jabbour, Henry N. |
author_facet | Maybin, Jacqueline A. Battersby, Sharon Hirani, Nikhil Nikitenko, Leonid L. Critchley, Hilary O. D. Jabbour, Henry N. |
author_sort | Maybin, Jacqueline A. |
collection | PubMed |
description | After menstruation, the endometrium has a remarkable capacity for repair, but the factors involved remain undefined. We hypothesize adrenomedullin (AM) plays a role in this process. Premenstrually progesterone levels decline, stimulating prostaglandin (PG) synthesis, vasoconstriction, and hypoxia. This study aimed to determine 1) AM expression throughout the menstrual (M) cycle and 2) its regulation by PG and hypoxia. Human endometrial biopsies (n = 51) were collected with ethical approval and consent. AM mRNA expression was examined by quantitative RT-PCR and was found to be selectively elevated in endometrium from the menstrual (M) phase (P < 0.001). AM immunohistochemical staining was maximal in M and proliferative (P) endometrium. Culture of secretory, but not P, explants with 100 nm PGF(2α) or hypoxia (0.5% O2) increased AM mRNA (P < 0.05). P explants were induced to increase AM expression using in vitro progesterone withdrawal but required the presence of hypoxia (P < 0.05). Short hairpin sequences against hypoxia-inducible factor-1α (HIF-1α) inhibited AM hypoxic up-regulation but did not alter PGF(2α)-induced expression. The AM receptor was immunolocalized to endothelial cells in both lymphatic and blood vessels. Conditioned medium from PGF(2α)-treated cells increased endothelial cell proliferation and branching (P < 0.05). This was abolished by AM receptor antagonists. In conclusion, AM is elevated at the time of endometrial repair and induces both angiogenesis and lymphangiogenesis by stimulating endothelial cell proliferation and tube formation. In the human endometrium, AM expression is up-regulated by two mechanisms: a HIF-1α-mediated hypoxic induction and a HIF-1α-independent PGF(2α) pathway. These physiological mechanisms may provide novel therapeutic targets for disorders such as heavy menstrual bleeding. |
format | Online Article Text |
id | pubmed-3192419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-31924192011-10-13 The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair Maybin, Jacqueline A. Battersby, Sharon Hirani, Nikhil Nikitenko, Leonid L. Critchley, Hilary O. D. Jabbour, Henry N. Endocrinology Reproduction-Development After menstruation, the endometrium has a remarkable capacity for repair, but the factors involved remain undefined. We hypothesize adrenomedullin (AM) plays a role in this process. Premenstrually progesterone levels decline, stimulating prostaglandin (PG) synthesis, vasoconstriction, and hypoxia. This study aimed to determine 1) AM expression throughout the menstrual (M) cycle and 2) its regulation by PG and hypoxia. Human endometrial biopsies (n = 51) were collected with ethical approval and consent. AM mRNA expression was examined by quantitative RT-PCR and was found to be selectively elevated in endometrium from the menstrual (M) phase (P < 0.001). AM immunohistochemical staining was maximal in M and proliferative (P) endometrium. Culture of secretory, but not P, explants with 100 nm PGF(2α) or hypoxia (0.5% O2) increased AM mRNA (P < 0.05). P explants were induced to increase AM expression using in vitro progesterone withdrawal but required the presence of hypoxia (P < 0.05). Short hairpin sequences against hypoxia-inducible factor-1α (HIF-1α) inhibited AM hypoxic up-regulation but did not alter PGF(2α)-induced expression. The AM receptor was immunolocalized to endothelial cells in both lymphatic and blood vessels. Conditioned medium from PGF(2α)-treated cells increased endothelial cell proliferation and branching (P < 0.05). This was abolished by AM receptor antagonists. In conclusion, AM is elevated at the time of endometrial repair and induces both angiogenesis and lymphangiogenesis by stimulating endothelial cell proliferation and tube formation. In the human endometrium, AM expression is up-regulated by two mechanisms: a HIF-1α-mediated hypoxic induction and a HIF-1α-independent PGF(2α) pathway. These physiological mechanisms may provide novel therapeutic targets for disorders such as heavy menstrual bleeding. Endocrine Society 2011-07 2011-05-10 /pmc/articles/PMC3192419/ /pubmed/21558311 http://dx.doi.org/10.1210/en.2010-1256 Text en Copyright © 2011 by The Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Reproduction-Development Maybin, Jacqueline A. Battersby, Sharon Hirani, Nikhil Nikitenko, Leonid L. Critchley, Hilary O. D. Jabbour, Henry N. The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair |
title | The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair |
title_full | The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair |
title_fullStr | The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair |
title_full_unstemmed | The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair |
title_short | The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair |
title_sort | expression and regulation of adrenomedullin in the human endometrium: a candidate for endometrial repair |
topic | Reproduction-Development |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192419/ https://www.ncbi.nlm.nih.gov/pubmed/21558311 http://dx.doi.org/10.1210/en.2010-1256 |
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