@article{1a786ebdfa5b47f1be49492c9f789fa6,
title = "Feed-forward inhibition of androgen receptor activity by glucocorticoid action in human adipocytes",
abstract = "We compared transcriptomes of terminally differentiated mouse 3T3-L1 and human adipocytes to identify cell-specific differences. Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation. The AR agonist dihydrotestosterone (DHT) inhibited human adipocyte maturation by downregulation of adipocyte marker genes, but not in 3T3-L1. It is interesting that AR induction corresponded with dexamethasone activation of the glucocorticoid receptor (GR); however, when exposed to the differentiation cocktail required for adipocyte maturation, AR adopted an antagonist conformation and was transcriptionally repressed. To further explore effectors within the cocktail, we applied an image-based support vector machine (SVM) classification scheme to show that adipocyte differentiation components inhibit AR action. The results demonstrate human adipocyte differentiation, via GR activation, upregulates AR but also inhibits AR transcriptional activity.",
author = "Hartig, {Sean M.} and Bin He and Newberg, {Justin Y.} and Ochsner, {Scott A.} and Loose, {David S.} and Lanz, {Rainer B.} and McKenna, {Neil J.} and Buehrer, {Benjamin M.} and McGuire, {Sean E.} and Marco Marcelli and Mancini, {Michael A.}",
note = "Funding Information: This work was funded by National Institutes of Health (NIH) Grant 5R01DK055622, the Hankamer Foundation, and the U.S. Department of Defense Prostate Cancer Research Program (DAMD W81XWH-10-1-0390), with pilot grant and equipment support from the John S. Dunn Gulf Coast Consortium for Chemical Genomics (M.A.M.). Additional funding was provided by NIH Grants 1F32DK85979 (S.M.H.), 5T32HD007165 (to B.W. O{\textquoteright}Malley), 5K01DK081446 (B.H.), 5K12DK083014 (to D.J. Lamb), 3U19DK062434 (Nuclear Receptor Signaling Atlas), and the Caroline Weiss Law Foundation (S.E.M.). Imaging resources were supported by NIH Grants SCCPR U54 HD-007495 (to F.J. DeMayo), P30 DK-56338 (to M.K. Estes), P30 CA-125123 (to C.K. Osborne), and the Dan L. Duncan Cancer Center of Baylor College of Medicine. The authors thank Huiying Sun, Maureen G. Mancini, Leoncio Vergara, and Jim Broughman for technical resource support. The authors also thank Nancy Weigel and Fabio Stossi for critical review of the manuscript. B.B. is an employee of Zen Bio, Inc. ",
year = "2012",
month = sep,
day = "21",
doi = "10.1016/j.chembiol.2012.07.020",
language = "English (US)",
volume = "19",
pages = "1126--1141",
journal = "Chemistry and Biology",
issn = "1074-5521",
publisher = "Elsevier Inc.",
number = "9",
}