ANDROGEN INSENSITIVITY (AI) IN 43 PATIENTS: CLASSIFICATION BASED ON CLINICAL AND ANDROGEN RECEPTORS (AR) PHENOTYPES

Abstract

Androgen binding was studied in genital skin fibroblasts (GSF) established from XY patients with testes displaying signs of complete androgen insensitivity syndrome (CAIS, n = 14) and partial AIS (n = 29). Total whole-cell AR concentration (Bmax) in GSF strains derived from 31 normal circumcised boy's was 775 ± 185 × 10−18 mol/μg DNA (mean ± SD). The AR phenotype was receptor-negative in 79% of CAIS patients; however, the remaining 21% in this series had supranormal AR concentrations (mean 1840, range 1541 - 2072 × 10−18 mol/μg DNA). Further studies on these cell strains showed stable androgen binding at 40°C, normal dissociation rate for the AR complex, appropriate GSF cytosol sedimentation on sucrose density gradients in the presence of molybdate and 60% binding of the androgen ligand located in the nuclei. Only 7% of GSF strains from patients with PAIS were AR-negative; mean ± SD concentration of AR in the remainder was 837 ± 315 × 10−18 mol/μg DNA. No PAIS cell strain contained a supranormal AR concentration. More than 90% of AR-positive cell strains (including those with supranormal AR levels) responded by further augmenting total cellular AR concentration following prolonged androgen preincubation of GSF. This AR phenotype is not the result of a mutation affecting the gene coding for the AR protein.