HUMAN COMPLETE ANDROGEN INSENSITIVITY WITH NORMAL DIHYDROTESTOSTERONE RECEPTOR-BINDING CAPACITY IN CULTURED GENITAL SKIN FIBROBLASTS - EVIDENCE FOR A QUALITATIVE ABNORMALITY OF THE RECEPTOR

Complete androgen insensitivity syndrome (CAIS), or so-called testicular feminization, results from the lack of androgen action on target organs. Within this syndrome, 2 major variants have been described. In the 1st variant, the specific intracellular androgen receptors are undetectable (CAIS, AR-), whereas normal levels of androgen receptors are measured in the 2nd variant (CAIS, AR+). In studies with cultured labial skin fibroblasts of 3 CAIS, AR+ patients from the same family, their androgen receptors present qualitative differences when compared to normal receptors: Kd of 5.alpha.-dihydrotestosterone for the receptor is higher than normal. The in vitro dissociation rate of the receptor-steroid complex is faster than normal: the cellular androgen receptor is more thermolabile than normal when cells are exposed to superphysiological temperatures. 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 5.alpha.-dihydrotestosterone) probably do not explain the total lack of androgen action in these patients. 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+.