Some properties of the specific androgen-binding activities in cultured human genital skin fibroblasts.

Specific 5 alpha-dihydrotestosterone (DHT)-binding activity in the cytosol (C) and 0.4 M KCl-extractable nuclear fraction (N) of cultured human fibroblast cell strains developed from preputial (n = 12) and labium majus (n = 12) skin were analyzed by gel exclusion chromatography, sucrose gradient sedimentation, and thermostability. Both fractions had activities that were excluded from Sephacryl S-200 columns; another component (mol wt, 20,000) was present in the N fraction. The C was more thermostable than a homologous N activity, and addition to the former of KCl to 0.4 M had no effect. There was large, overlapping variation in thermostability of the C and N activities among strains from either site, sister strains developed from a single skin biopsy, and even among serial subcultures within a strain; likewise, the variable sedimentability of the C (4-7S) and N (3.2-5.9S) activities prevented their consistent discrimination. Each type of variation occurred despite excellent intraexperimental replication. The thermostability of a given N activity varied directly with its sedimentation coefficient. By cluster analysis, the data relating thermostability of a given N activity with the percentage of 0.4 M KCl-resistant nuclear activity segregated into two populations; within each population these two measurements were related inversely. We suggest that these coordinate behaviors of the N activity reflect intrinsic properties of the androgen-receptor system in normal genital skin fibroblasts which may be useful for defining qualitative aberrations of the system in receptor-positive forms of congenital androgen insensitivity.