Human complete androgen insensitivity with normal dihydrotestosterone receptor binding capacity in cultured genital skin fibroblasts: Evidence for a qualitative abnormality of the receptor

Terry R. Brown, Marc Maes, Stephen W. Rothwell, Claude J. Migeon

Research output: Contribution to journalArticle

Abstract

Complete androgen insensitivity syndrome (CAIS), or so-called testicular feminization, results from the lack of androgen action on target organs. Within this syndrome, two major variants have been described. In the first variant, the specific intracellular androgen receptors are undetectable (CAIS, AR), whereas normal levels of androgen receptors are measured in the second variant (CAIS, AR+). From studies with cultured labial skin fibroblasts of three CAIS, AR+ patients from the same family, we have demonstrated that their androgen receptors present qualitative differences when compared to normal receptors: 1) the apparent affinity constant (Kd) of 5βdihydrotestosterone for the receptor is higher than normal; 2) the in vitro dissociation rate of the receptor-steroid complex is faster than normal: 3) the cellular androgen receptor is more thermolabile than normal when cells are exposed to superphysiological temperatures; and 4) the relative binding affinity of the androgen receptor for progesterone is greater than normal. These findings suggest the presence of a structural abnormality of the androgen receptor in patients with CAIS, AR+. However, these changes (e.g. slightly decreased affinity of the receptor for 5a-dihydrotestosterone) probably do not explain the total lack of androgen action in these patients. Finally, the present data from this family along with those from the literature suggest the presence of heterogeneity as to the cause of the defect in CAIS, AR+.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume55
Issue number1
DOIs
StatePublished - Jul 1982

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Human complete androgen insensitivity with normal dihydrotestosterone receptor binding capacity in cultured genital skin fibroblasts: Evidence for a qualitative abnormality of the receptor'. Together they form a unique fingerprint.

  • Cite this