Androgen insensitivity

Am J Med Genet. 1999 Dec 29;89(4):210-7. doi: 10.1002/(sici)1096-8628(19991229)89:4<210::aid-ajmg5>;2-p.


The androgen receptor (AR) protein regulates transcription of certain genes. Usually, this activity depends upon a central DNA-binding domain that permits the binding of androgen-AR complexes to regulatory DNA sequences near or in a target gene. The AR also has a C-terminal androgen-binding domain (ABD) and an N-terminal modulatory domain. These domains interact among themselves and with coregulatory, nonreceptor proteins to determine vector control over a gene's transcription rate. The precise roles of these proteins are active research areas. Severe X-linked androgen receptor gene (AR) mutations cause complete androgen insensitivity, mild ones impair virilization with or without infertility, and moderate ones sometimes yield a wide phenotypic spectrum among sibs. Different expressivity may reflect variability of AR-interactive proteins. The family history must identify heterozygous XX females with sparse, delayed, or asymmetric pubic/axillary hair or delayed menarche and infertile XY maternal aunts or uncles. Mutation type and density vary along the length of the AR. N-terminal polyglutamine tract expansion limits AR transactivation, causing a form of mild androgen insensitivity. Analysis of ABD mutations that do not impair androgen binding or impair it selectively will illuminate its intradomain properties. For partial androgen insensitivity and mild androgen insensitivity, pharmacotherapy with certain androgens or other steroids may overcome some dysfunction of certain mutant ARs. Experience with this approach is limited; outcomes have been generally disappointing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgen-Insensitivity Syndrome / diagnosis
  • Androgen-Insensitivity Syndrome / genetics*
  • Androgen-Insensitivity Syndrome / pathology
  • Androgen-Insensitivity Syndrome / therapy
  • Female
  • Genotype
  • Humans
  • Infertility, Male / genetics
  • Male
  • Mutation
  • Phenotype
  • Puberty / genetics
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / genetics*
  • Spermatogenesis / genetics
  • Structure-Activity Relationship
  • Trinucleotide Repeats / genetics
  • X Chromosome / genetics


  • Receptors, Androgen