Sexual differentiation of hepatic steroid metabolism in the rat

Steroid metabolizing enzyme activities in rat liver may be classified according to their regulation. One group consists of enzymes, the activities of which are irreversibly determined at birth by androgens, a second group encompasses enzymes that are reversibly affected by androgens and a third group is made up of enzymes essentially independent of androgens. The mechanisms by which androgens influence hepatic enzyme activities are still not clear but the hypophysis seems to be essential for the sexual differentiation of liver metabolism in the rat. Possibly this control is exerted by a hypophyseal feminizing factor that feminizes a basal masculine enzyme pattern in rat liver. Some kind of direct androgen action on the liver cell may also be postulated since a radioactively labelled complex between 4-androstene-3,17-dione and a high affinity protein can be extracted from liver cytosol and nuclei after intrapertitoneal administration of [1,2,6,7-³H]-testosterone to castrated male and female rats. This androgen "receptor" moves as a 10 S protein when analysed by sucrose density gradient centrifugation, has a pI of about H5 when analysed by isoelectric focusing and is selectively concentrated in unlabelled liver nuclei when these are incubated with liver cytosol containing labelled androgen-protein complex.