ANDROGEN INSENSITIVITY SYNDROME (ATS): CELLULAR RESPONSES TO ANDROGENS

Abstract

A considerable number of hereditary defects in the mechanism of action of testosterone (T) is known. Most, but not all, can be traced back to either a functionally deficient receptor or a defect in the 5-alpha reductase activity. The current (in vitro) diagnostic approach involves cell culture of genital skin derived fibroblasts followed by studies of whole cell dihydrotestosterone (DHT) or R1881 uptake and the kinetics of T reduction.Several receptor abnormalities can be detected only under special conditions: lability at 42°C; increased dissociation rate of the androgen receptor complex; different behaviour in the absence of molybdate, etc. A more or less complete investigation is therefore extremely time consuming, while in a significant percentage of all patients with the clinical diagnosis AIS, the diagnosis cannot be confirmed or excluded by means of laboratory studies. Therefore, we tried a functional approach: fibroblasts were stimulated for 6 days with T and DHT, followed by 25S-methionine pulse-labeling. Labeled proteins were separated by means of 1- and 2-dimensional electrophoresis and detected by autoradiography. We found no evidence for the induction of new proteins, but the results suggest that under these conditions in normal androgen-responsive cells at least one protein disappears. In AIS patients no such repression was seen. This functional approach is able to corroborate and complement the “classical” receptor studies.