Kinetic evidence for a unique testosterone-receptor complex in 5 alpha-reductase sufficient genital skin fibroblasts and the effects of 5 alpha-reductase deficiency on its formation.

When 5 alpha-reductase-sufficient genital skin fibroblast (GSF) monolayers are incubated with testosterone (T), they first form androgen (A)-receptor (R) complexes that dissociate at a fast rate [k(37 degrees C = 0.024 min-1]. As T is converted to 5 alpha-dihydrotestosterone (DHT), this population of T-R complexes is eventually replaced by one that dissociates much more slowly [k(37 degrees C) = 0.006 min-1], at a rate typical of DHT-R complexes. During the course of T to DHT conversion, one may observe a population of A-R complexes that has a linear (monophasic) intermediate dissociation rate constant [k(37 degrees C) = 0.012 min-1]; this population cannot simply reflect a mixture of T- and DHT-R complexes. The rate at which the complexes are processed from one dissociative form to the next varies with the incubation temperature and the presence or absence of serum in the medium; it also varies within and among GSF strains under apparently constant conditions. To explain these facts, we propose a model that enables the 5 alpha-reductase enzyme to influence the processive dissociative behaviour of T-R complexes by engaging in some sort of coupling with the AR. The proposal is strengthened by a set of observations in cells with constitutive, mendelian or inhibitor-induced 5 alpha-reductase deficiency that preclude a simple quantitative relation between A-R complex processing and the extent of T to DHT conversion.