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International Journal of Medicinal Chemistry
Volume 2013 (2013), Article ID 203606, 8 pages
http://dx.doi.org/10.1155/2013/203606
Research Article

Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors

1Department of Integrative Life Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA
2Virginia Commonwealth University Reanimation Engineering Science Center (VCURES), Virginia Commonwealth University, Richmond, VA 23298, USA
3Department of Biochemistry, Virginia Commonwealth University, 1101 E. Marshall Street, Sanger Hall, Room 2-004, Richmond, VA 23298, USA
4Hunter Holmes McGuire VA Medical Center, Richmond, VA 23249, USA
5Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA
6Massey Cancer Center, Richmond, VA 23298, USA
7Michigan Critical Injury and Illness Research Center, Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48109, USA
8Department 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.