Feed-forward inhibition of androgen receptor activity by glucocorticoid action in human adipocytes

Sean M. Hartig, Bin He, Justin Y. Newberg, Scott A. Ochsner, David S. Loose, Rainer B. Lanz, Neil J. McKenna, Benjamin M. Buehrer, Sean E. McGuire, Marco Marcelli, Michael A. Mancini

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1126-1141
Number of pages16
JournalChemistry and Biology
Volume19
Issue number9
DOIs
StatePublished - Sep 21 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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