Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors
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 ERβmay 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 04, 2013
- Source ID
- 10.1155/2013/203606
Entities
People
- Charles E. Chalfant
- Dayanjan S. Wijesinghe
- Kevin R. Ward
- Robert F. Diegelmann
- Roger M. Loria
- Thomas L. Shaak
Organizations
- Hunter Holmes McGuire Veterans Administration Medical Center
- United States Army Medical Research and Development Command
- University of Michigan
- Virginia Commonwealth University