Androgen receptor in rat liver: Hormonal and developmental regulation of the cytoplasmic receptor and its correlation with the androgen-dependent synthesis of α2u- globulin

Abstract

The cytoplasmic receptor for 5α-dihydrotestosterone has been identified in the rat liver and partially characterized. The receptor is a protein with a sedimentation coefficient of 3.5 S and binds both androgens (5α-dihydrotestosterone and testosterone) and estradiol-17β with high affinity. At saturating concentration, for every mole of estradiol there seem to be three moles of 5α-dihydrotestosterone bound to the receptor. Whereas estradiol stronly inhibits the uptake of 5α-dihydrotestosterone by the receptor, the presence of 5α-dihydrotestosterone only weakly interferes with estradiol binding. The level of the androgen receptor activity in the hepatic cytosol was found to follow closely the level of the urinary output of α- 2u-globulin, an androgen-dependent protein of hepatic origin. Immature and senile male as well as female rats, which do not normally produce α 2u-globulin, also lacked androgen receptor activity in their hepatic cytosol. Castration of the adult male rats results in a gradual drop of the urinary output of α 2u-globulin as well as of the hepatic androgen receptor activity. Androgen treatment of immature and senile male rats does not induce α 2u-globulin or any receptor activity. Administration of estradiol to adult male rates results in complete inhibition of both α 2u-synthesis as well as complete loss of the cytosol androgen receptor activity in these animals. These results strongly indicate that the hepatic the hepatic androgen receptor activity. Androgen treatment of immature and senile male rats does not induce α 2u-globulin or any receptor activity. Administration of estradiol to adult male rats results in complete inhibition of boty α 2u-synthesis as well as complete loss of the cytosol androgen receptor activity in these animals. These results strongly indicate that the hepatic androgen receptor is an inducible protein whose synthesis is regulated by its own ligands, the androgens acting as the positive and the estradiol as the negative signals.