Androgen receptor: Structural domains and functional dynamics after ligand-receptor interaction

Arun K. Roy, Rakesh K. Tyagi, Chung S. Song, Yan Lavrovsky, Soon C. Ahn, Tae Sung Oh, Bandana Chatterjee

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Androgens are C-19 steroids secreted primarily from the testes and adrenals that play a critical role in reproduction. Reproductive functions of androgens are mediated through coordination of diverse physiological processes ranging from brain functions to specific cell proliferation and apoptosis. At the molecular level, most of these regulatory influences are exerted by altered expression of appropriate genes by the androgen receptor (AR), a member of the nuclear receptor (NR) superfamily. The unliganded AR is a cytoplasmic protein and, upon ligand binding, it translocates into the nucleus. Thereafter, in conjunction with other transcription factors and coactivators, the AR influences transcription of target genes through a multistep process that includes its clustering in a subnuclear compartment. Here, we describe the genomic organization of the AR, the role of individual structural domains in specific AR function, and the influence of agonistic/antagonistic ligands in the intracellular movement of the receptor. We also show that the AR is capable of undergoing multiple rounds of nucleocytoplasmic recycling after ligand binding and dissociation. Xenobiotic ligands, considered as selective androgen receptor modulators (SARMs), can modulate AR activity by inhibiting either its nuclear translocation or its subnuclear clustering and subsequent transactivation function.

Original languageEnglish (US)
Pages (from-to)44-57
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volume949
DOIs
StatePublished - 2001

Keywords

  • Androgen receptor
  • Chlozolinate
  • Endocrine disrupters
  • Green fluorescent protein
  • Procymidone
  • Receptor recycling
  • SARM
  • Vinclozolin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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