Testosterone induced downregulation of migration and proliferation in human Umbilical Vein Endothelial Cells by Androgen Receptor dependent and independent mechanisms

Aulona Gaba, Mario Mairhofer, Zyhdi Zhegu, Nadja Leditznig, Ladislaus Szabo, Walter Tschugguel, Christian Schneeberger, Iveta Yotova

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Recent research has emphasized the potential unfavorable effects of declining testosterone (T) levels in men and the putative beneficial effect of androgen therapy in select women. Some controversy surrounding the mechanism of action and the effects of T on endothelium remains. In this study, we evaluated the mechanism of T action on pooled primary Human Umbilical Vein Endothelial Cells (HUVEC) of mixed gender by focusing on two important processes, proliferation and migration. In our in vitro model system, we found that only the supra-physiological dose of T affected these two processes irrespective of the ratio of male to female cells in the pools. At a concentration of 1 μM, T downregulated the proliferation of HUVEC by inducing arrest in the G1 cell cycle phase in an Androgen Receptor (AR)-independent manner. We show that treatment with 1 μM T also induced downregulation of HUVEC migration. This process was AR-dependent and was associated with persistent phosphorylation of ezrin, radixin and moesin. Regardless of the mechanism of action, the treatment of HUVEC with both supra- and physiological doses of T was associated with posttranscriptional stabilization of the AR upon ligand binding.

Original languageEnglish
Pages (from-to)173-184
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume476
DOIs
Publication statusPublished - 15 Nov 2018

Keywords

  • Androgen
  • Endothel
  • HUVEC
  • Migration
  • Proliferation
  • Testosterone
  • Up-Regulation/drug effects
  • Down-Regulation/drug effects
  • Cell Movement/drug effects
  • Humans
  • Apoptosis/drug effects
  • Male
  • Testosterone/pharmacology
  • Human Umbilical Vein Endothelial Cells/cytology
  • Protein Stability/drug effects
  • Cation Transport Proteins/genetics
  • Cell Cycle Checkpoints/drug effects
  • Female
  • Cell Proliferation/drug effects
  • Cyclin-Dependent Kinase Inhibitor p21/metabolism
  • Transcription, Genetic/drug effects
  • Receptors, Androgen/metabolism

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