Androgen action

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Androgens are C-19 steroids that provide major regulatory influences on male reproductive function. Testosterone, the principal androgenic steroid, is secreted by the Leydig cells of the testes. Both testosterone and its 5α reduced derivative 5α-dihydrotestosterone (DHT) are physiological ligands for the androgen receptor (AR). Ligand activated AR acts as a nuclear transcription factor and mediates androgen action. AR, along with receptors for a number of C-21 steroids such as glucocorticoid, mineralocorticoid, and progesterone, share the same 15 base pair consensus element composed of 5'- GGA/TACAnnnTGTTCT-3'. Despite this cross reactivity at the level of the DNA, physiologically, androgens regulate their target genes with a high degree of receptor specificity. Such a regulatory specificity appears to be due to multiphasic interactions involving enzymatic activation/inactivation of the steroid ligand, interaction with specific receptor-associated nuclear factors on or around the hormone response element, and differential regulation of the receptor gene expression. Conversion of testosterone to 5α- dihydrotestosterone in target cells is a widespread activation mechanism that amplifies the androgenic signal. Unlike the testosterone-AR complex, DHT- activated AR has a longer half-life, and thus prolongs androgen action. Oxido-reduction of androgens by 17β-hydroxysteroid dehydrogenase and sulfurylation by androgen sulfotransferase are two major pathways of androgen inactivation in target cells. Prenatal deprivation of androgen action, due to mutations in either the AR or the 5α-reductase gene, results in developmental abnormalities of male reproductive tissues and also cause partial or complete androgen-insensitivity syndromes. Elucidation of various molecular steps in androgen action is allowing development of improved therapeutic agents for the management of disorders of androgen action such as the prostatic hypertrophy and neoplasia.

Original languageEnglish (US)
Pages (from-to)157-176
Number of pages20
JournalCritical Reviews in Eukaryotic Gene Expression
Volume5
Issue number2
StatePublished - 1995

Fingerprint

Androgens
Androgen Receptors
Dihydrotestosterone
Steroids
Testosterone
Ligands
Androgen-Insensitivity Syndrome
Sulfotransferases
Mineralocorticoids
Leydig Cells
Prostatic Hyperplasia
Gene Expression Regulation
Response Elements
Cytoplasmic and Nuclear Receptors
Base Pairing
Glucocorticoids
Genes
Progesterone
Half-Life
Testis

Keywords

  • androgen receptor
  • androgen-insensitivity syndrome
  • steroid hormone
  • testosterone
  • transacting factor

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Androgen action. / Roy, A. K.; Chatterjee, Bandana.

In: Critical Reviews in Eukaryotic Gene Expression, Vol. 5, No. 2, 1995, p. 157-176.

Research output: Contribution to journalArticle

Roy, A. K. ; Chatterjee, Bandana. / Androgen action. In: Critical Reviews in Eukaryotic Gene Expression. 1995 ; Vol. 5, No. 2. pp. 157-176.
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