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Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by androgen excess and ovarian dysfunction and presents with increased cardiometabolic risk factors such as obesity, insulin resistance, and elevated blood pressure (BP). We previously...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065488/ https://www.ncbi.nlm.nih.gov/pubmed/30087950 http://dx.doi.org/10.1210/js.2018-00131 |
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author | Torres Fernandez, Edgar D Adams, Kristen V Syed, Maryam Maranon, Rodrigo O Romero, Damian G Yanes Cardozo, Licy L |
author_facet | Torres Fernandez, Edgar D Adams, Kristen V Syed, Maryam Maranon, Rodrigo O Romero, Damian G Yanes Cardozo, Licy L |
author_sort | Torres Fernandez, Edgar D |
collection | PubMed |
description | Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by androgen excess and ovarian dysfunction and presents with increased cardiometabolic risk factors such as obesity, insulin resistance, and elevated blood pressure (BP). We previously reported that administration of dihydrotestosterone (DHT) to female rats elicits cardiometabolic derangements similar to those found in women with PCOS. In this study, we tested the hypothesis that the DHT-mediated cardiometabolic derangements observed in PCOS are long lasting despite DHT withdrawal. Four-week-old female Sprague Dawley rats were treated with DHT (7.5 mg/90 days) or placebo for 6 months. DHT was discontinued (ex-DHT), and rats were followed for 6 additional months. After 6 months of DHT withdrawal, food intake, body weight, fat and lean mass, fasting plasma insulin, leptin, and adiponectin were elevated in ex-DHT rats. BP remained significantly elevated, and enalapril, an angiotensin-converting enzyme (ACE) inhibitor, normalized BP in ex-DHT rats. Expression of components of the intrarenal renin-angiotensin system was increased in ex-DHT rats. The cardiometabolic features found in ex-DHT rats were associated with lower plasma androgen levels but increased expression of renal and adipose tissue androgen receptors. In summary, androgen-induced cardiometabolic effects persisted after DHT withdrawal in a PCOS experimental model. Activation of intrarenal renin-angiotensin system plays a major role in the androgen-mediated increase in BP in ex-DHT. Upregulation of the renal and adipose tissue androgen receptor may explain the long-lasting effects of androgens. In clinical scenarios characterized by hyperandrogenemia in women, prompt normalization of androgen levels may be necessary to prevent their long-lasting cardiometabolic effects. |
format | Online Article Text |
id | pubmed-6065488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-60654882018-08-07 Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome Torres Fernandez, Edgar D Adams, Kristen V Syed, Maryam Maranon, Rodrigo O Romero, Damian G Yanes Cardozo, Licy L J Endocr Soc Research Articles Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by androgen excess and ovarian dysfunction and presents with increased cardiometabolic risk factors such as obesity, insulin resistance, and elevated blood pressure (BP). We previously reported that administration of dihydrotestosterone (DHT) to female rats elicits cardiometabolic derangements similar to those found in women with PCOS. In this study, we tested the hypothesis that the DHT-mediated cardiometabolic derangements observed in PCOS are long lasting despite DHT withdrawal. Four-week-old female Sprague Dawley rats were treated with DHT (7.5 mg/90 days) or placebo for 6 months. DHT was discontinued (ex-DHT), and rats were followed for 6 additional months. After 6 months of DHT withdrawal, food intake, body weight, fat and lean mass, fasting plasma insulin, leptin, and adiponectin were elevated in ex-DHT rats. BP remained significantly elevated, and enalapril, an angiotensin-converting enzyme (ACE) inhibitor, normalized BP in ex-DHT rats. Expression of components of the intrarenal renin-angiotensin system was increased in ex-DHT rats. The cardiometabolic features found in ex-DHT rats were associated with lower plasma androgen levels but increased expression of renal and adipose tissue androgen receptors. In summary, androgen-induced cardiometabolic effects persisted after DHT withdrawal in a PCOS experimental model. Activation of intrarenal renin-angiotensin system plays a major role in the androgen-mediated increase in BP in ex-DHT. Upregulation of the renal and adipose tissue androgen receptor may explain the long-lasting effects of androgens. In clinical scenarios characterized by hyperandrogenemia in women, prompt normalization of androgen levels may be necessary to prevent their long-lasting cardiometabolic effects. Endocrine Society 2018-07-10 /pmc/articles/PMC6065488/ /pubmed/30087950 http://dx.doi.org/10.1210/js.2018-00131 Text en Copyright © 2018 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Articles Torres Fernandez, Edgar D Adams, Kristen V Syed, Maryam Maranon, Rodrigo O Romero, Damian G Yanes Cardozo, Licy L Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome |
title | Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome |
title_full | Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome |
title_fullStr | Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome |
title_full_unstemmed | Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome |
title_short | Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome |
title_sort | long-lasting androgen-induced cardiometabolic effects in polycystic ovary syndrome |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065488/ https://www.ncbi.nlm.nih.gov/pubmed/30087950 http://dx.doi.org/10.1210/js.2018-00131 |
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