[The role of the hypophysis and the hypophyseal hormone prolactin in maintenance of the sexual specificity of the metabolism of testosterone and 5-alpha-dihydrotestosterone in rat liver slices].

Hypophysectomy of rats 55 days after birth causes profound changes in the sexually differentiated liver metabolism of testosterone and 5alpha-dihydrotestosterone, which were studied when the rats were 80 days old. 1. Metabolism of testosterone after hypophysectomy: The turnover of testosterone decreased significantly to the same level in both sexes. The effect was especially marked in the female, which normally has a high turnover of this compound. The sexual differences in the patterns of metabolites were also lost, owing to the following changes: In the male, the high level of metabolites of the 3beta-hydroxy-5alpha-androstane type falls to the low level found in the female controls. The low level of 4-androstene-3,17-dione in the female increases to the high level found in the male controls. The concentrations of testosterone increase and those of the metabolites of the 3-oxo- and 3alpha-hydroxy-5alpha-androstane decrease to values that are significantly much higher or lower, respectively, than the normal values found in the control animals. 2. Metabolism of 5alpha-dihydrotestosterone after hypophysectomy: In comparison with the controls, the turnover of this substrate is significantly decreased by the same factor in both sexes; thus the difference between the sexes persists. In the pattern of metabolites, the sexual differences are still apparent, but less marked. The levels of metabolites show two opposing changes: a significant increase in the concentration of 3beta-hydroxy metabolites, and a significant decrease in the concentration of 3alpha-hydroxy metabolites; although the activity of the microsomal 3alpha-hydroxysteroid dehydrogenase increases by a factor of 3 - 4 in both sexes after hypophysectomy[1]. This discrepancy indicates a compartmentalization of androgen metabolism in the liver cell, in which delta4-5alpha- and 3beta-hydrogenation occur on the membranes of the endoplasmic reticulum, whereas 3alpha-hydrogenation occurs in the cytosol. 3. Action of prolactin on the metabolism of testosterone in hypophysectomized animals: Prolactin (125 mug twice daily from the 70th to the 79th day of life) causes a significant acceleration of the delta4-5alpha-hydrogenation, which is recognized as a significant increase in the concentrations of 5alpha-androstane metabolites; the 3beta-hydroxy compounds in both sexes reach the normal level of male control animals. The significant increase in the concentration of 3alpha-hydroxy compounds is accompanied by a partial reestablishment of the sexual differences. The sex differences in androgen turnover and metabolite pattern are subject to a hypophyseal regulation, which is separate from the gonadotropic partial function. The hydroxylation activity of the liver, measured as the production of C19O3-steroids, is not significantly affected by hypophysectomy or by treatment with prolactin.