Possible implications of the comparative dissociative behavior of testosterone- and 5 alpha-dihydrotestosterone-receptor complexes formed by human skin fibroblasts.
We have studied the dissociative behavior of 5 alpha-dihydrotestosterone (DHT)- or testosterone (T)-receptor complexes extracted from normal and 5 alpha-reductase-deficient human genital skin fibroblasts, respectively. The rate at which each hormone dissociates from the androgen receptor is temperature-dependent (29-40 degrees C), but DHT does so in a first-order (monophasic) manner, while T yields complex (biphasic) dissociation kinetics. Prior exposure to 0.1 M sodium thiocyanate induces DHT-receptor complexes to dissociate with complex kinetics. The temperature dependence of these complex dissociation profiles can be simulated identically by a kinetic model involving three conformational states of the androgen-receptor complex. Neither the rate constants of the rapidly- or slowly-dissociating components of T-receptor dissociation, nor the magnitude of the latter are affected by sodium molybdate (5 mM). Similarly, neither sodium molybdate nor potassium chloride (0.1-0.3 M) alters the complex dissociative behavior of DHT-receptor complexes that is induced by 0.1 M sodium thiocyanate.
D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013696:Temperature; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism
D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D013739:Testosterone