Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid ReceptorsReportar como inadecuado




Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

International Journal of Medicinal ChemistryVolume 2013 2013, Article ID 203606, 8 pages

Research Article

Department of Integrative Life Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA

Virginia Commonwealth University Reanimation Engineering Science Center VCURES, Virginia Commonwealth University, Richmond, VA 23298, USA

Department of Biochemistry, Virginia Commonwealth University, 1101 E. Marshall Street, Sanger Hall, Room 2-004, Richmond, VA 23298, USA

Hunter Holmes McGuire VA Medical Center, Richmond, VA 23249, USA

Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA

Massey Cancer Center, Richmond, VA 23298, USA

Michigan Critical Injury and Illness Research Center, Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48109, USA

Department of Microbiology, Immunology, Pathology and Emergency Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA

Received 17 January 2013; Revised 27 February 2013; Accepted 14 March 2013

Academic Editor: Patrick Bednarski

Copyright © 2013 Thomas L. Shaak et al. 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.

Abstract

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.





Autor: Thomas L. Shaak, Dayanjan S. Wijesinghe, Charles E. Chalfant, Robert F. Diegelmann, Kevin R. Ward, and Roger M. Loria

Fuente: https://www.hindawi.com/



DESCARGAR PDF




Documentos relacionados