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Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors
DHEA, 17α-AED, 17β-AED, and 17β-AET exhibit strong biological activity that has been attributed to androgenic, estrogenic, or antiglucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED, and 17β-AET for their ability to activate the human AR, ER, and GR and determine...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981456/ https://www.ncbi.nlm.nih.gov/pubmed/24729874 http://dx.doi.org/10.1155/2013/203606 |
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author | Shaak, Thomas L. Wijesinghe, Dayanjan S. Chalfant, Charles E. Diegelmann, Robert F. Ward, Kevin R. Loria, Roger M. |
author_facet | Shaak, Thomas L. Wijesinghe, Dayanjan S. Chalfant, Charles E. Diegelmann, Robert F. Ward, Kevin R. Loria, Roger M. |
author_sort | Shaak, Thomas L. |
collection | PubMed |
description | DHEA, 17α-AED, 17β-AED, and 17β-AET exhibit strong biological activity that has been attributed to androgenic, estrogenic, or antiglucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED, and 17β-AET for their ability to activate the human AR, ER, and GR and determine the relative androgenicity, estrogenicity, and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR, only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors and their biological effects. |
format | Online Article Text |
id | pubmed-3981456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-39814562014-04-09 Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors Shaak, Thomas L. Wijesinghe, Dayanjan S. Chalfant, Charles E. Diegelmann, Robert F. Ward, Kevin R. Loria, Roger M. Int J Med Chem Research Article DHEA, 17α-AED, 17β-AED, and 17β-AET exhibit strong biological activity that has been attributed to androgenic, estrogenic, or antiglucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED, and 17β-AET for their ability to activate the human AR, ER, and GR and determine the relative androgenicity, estrogenicity, and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR, only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors and their biological effects. Hindawi Publishing Corporation 2013 2013-04-04 /pmc/articles/PMC3981456/ /pubmed/24729874 http://dx.doi.org/10.1155/2013/203606 Text en Copyright © 2013 Thomas L. Shaak et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Shaak, Thomas L. Wijesinghe, Dayanjan S. Chalfant, Charles E. Diegelmann, Robert F. Ward, Kevin R. Loria, Roger M. Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors |
title | Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors |
title_full | Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors |
title_fullStr | Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors |
title_full_unstemmed | Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors |
title_short | Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors |
title_sort | structural stereochemistry of androstene hormones determines interactions with human androgen, estrogen, and glucocorticoid receptors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981456/ https://www.ncbi.nlm.nih.gov/pubmed/24729874 http://dx.doi.org/10.1155/2013/203606 |
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