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Endocrinology, Vol 113, 1574-1581, Copyright © 1983 by Endocrine Society

ARTICLES

Transformation of human androgen receptors to the deoxyribonucleic acid- binding state

WJ Kovacs, JE Griffin and JD Wilson

The transformation of [3H]dihydrotestosterone-androgen receptor complexes to the nuclear binding state was studied in fibroblasts cultured from human genital skin, using binding of the androgen- receptor complex to DNA-cellulose as a measure of transformation. Transformation of cytosolic dihydrotestosterone-receptor complexes proceeded slowly at 0 C, and heating to 25 C caused rapid transformation that was essentially complete within 15 min. Sodium molybdate (up to 10 mM) slowed the rate of transformation in a concentration-dependent fashion; low concentrations of molybdate (0.5-1 mM) prevented transformation at 0 C, but transformation of up to 70% of the total cytosolic hormone-receptor complexes could be achieved in the presence of high concentrations of molybdate by appropriately prolonged heating at 25 C. Molybdate appeared to exhibit a dual effect, increasing the total amount of androgen-receptor complex recoverable in cytosol and prolonging the time course of heat-induced transformation. Treatment of cytosolic dihydrotestosterone-receptor complexes with 0.5 M NaCl caused a degree of transformation similar to that seen after heat treatment but was unaffected by 10 mM molybdate. Transformation was accompanied by disappearance of the 7S form of the receptor on sucrose density gradients, but there was no reciprocal increase in a smaller size binding moiety on low ionic strength sucrose density gradients. The heat-transformed receptor could be detected, however, as a 3S binding peak on gradients containing 0.3 M NaCl, suggesting that transformation was accompanied by a structural alteration of the hormone-receptor complex.


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F. W. George
Androgen Metabolism in the Prostate of the Finasteride-Treated, Adult Rat: A Possible Explanation for the Differential Action of Testosterone and 5{alpha}-Dihydrotestosterone during Development of the Male Urogenital Tract
Endocrinology, March 1, 1997; 138(3): 871 - 877.
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Copyright © 1983 by The Endocrine Society