Androgen receptor in human liver: characterization and quantitation in normal and diseased liver

Liver is responsive to sex hormones. The role of androgens in normal human liver function is not well understood, although androgens have been implicated in several liver diseases. Because the human hepatic androgen receptor has not been adequately characterized, we analyzed cytosolic and nuclear fractions from normal human liver of both sexes for androgen-binding activity using multipoint saturation analysis with the androgenic radioligand methyltrienelone (R1881). Both cytosolic and nuclear fractions of both sexes displayed high affinity R1881 binding (dissociation constants = nanomolar range). The R1881 binding in both fractions is highly specific in that potent androgens compete well, and the antiandrogens hydroxyflutamide and cyproterone acetate show partial competition; other nonandrogenic steroid hormones do not compete. The cytosolic R1881 receptor displays physicochemical characteristics of androgen receptors in other tissues in that it is retained by heparin-Sepharose and by DNA cellulose after activation, and it displays a molybdate-stabilized 8S form on sucrose gradients and a 7.3-nm species on gel filtration chromatography. Receptor activity was also quantitated in specimens of hepatic adenoma, focal nodular hyperplasia and metastatic carcinoma to the liver and in samples of adjacent histologically normal specimens when available. In general, both the diseased and normal portions of the livers from the patients with hepatic adenoma and metastatic carcinoma to the liver, but not focal nodular hyperplasia, demonstrated reduced total androgen-receptor activity as compared with liver from normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)