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Anabolic steroids, testosterone-precursors and virilizing androgens induce distinct activation profiles of androgen

P M Holterhus1, S Piefke, O Hiort

  • 1Department of Pediatrics, Medical University of Lübeck, Germany. holterhus@paedia.ukl.mu-luebeck.de

The Journal of Steroid Biochemistry and Molecular Biology
|February 19, 2003
PubMed

Insights

Different androgens exhibit varied biological effects due to distinct gene expression profiles. This study reveals that anabolic steroids and testosterone precursors activate the androgen receptor differently than virilizing androgens, impacting gene transcription.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Androgens, including testosterone and anabolic steroids, induce diverse biological effects.
  • The molecular mechanisms underlying these varied actions are not fully understood.
  • Steroid-specific gene expression profiles following androgen receptor activation are hypothesized to explain these differences.

Purpose of the Study:

  • To investigate androgen receptor (AR)-dependent transactivation profiles of different androgens.
  • To determine if structurally diverse androgens elicit distinct target gene expression patterns.
  • To explore the relationship between androgen structure and AR-mediated transcriptional activity.

Main Methods:

  • Utilized Chinese hamster ovary (CHO)-cells as an artificial model for androgen target genes.
  • Co-transfected cells with three distinct androgen-responsive promoter constructs: (ARE)(2)TATA-luc, MMTV-luc, and GRE-OCT-luc.
  • Tested a panel of androgens, including virilizing androgens, anabolic steroids, and testosterone precursors, at varying concentrations (0.001-100 nM).

Main Results:

  • All tested steroids effectively activated the androgen receptor.
  • Anabolic steroids and testosterone precursors displayed distinct promoter activation profiles compared to virilizing androgens.
  • Specifically, anabolic steroids and testosterone precursors showed significantly lower activation of the (ARE)(2)TATA-luc promoter.
  • Hierarchical clustering revealed two major branches: virilizing androgens and anabolics/testosterone-precursors, based on activation profiles.

Conclusions:

  • Steroid-specific differences in gene transcription profiles mediated by androgen receptor activation contribute to the varied biological actions of androgens.
  • The distinct activation patterns suggest a molecular basis for the differential effects of various androgenic compounds.
  • This finding has implications for understanding androgen signaling and the diverse effects of related compounds.

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