Developmental, diurnal and oestrous cycle-dependent changes in the activity of liver enzymes.

The metabolism of [4-14C]4-androstene-3, 17-dione was studied in the 105000 g microsomal and supernatant fractions of liver from developing rats of both sexes. The following enzyme activities were measured: 5beta-reductase (supernatant fraction) and 5alpha-reductase, 17alpha- and 17beta-hydroxysteroid reductases, 6beta-, 7alpha- and 16alpha-hydroxylases (microsomal fraction). The activities of the 3alpha- and 3beta-hydroxysteroid reductases were estimated by calculating the ratios of 3alpha-: 5alpha- and 3beta-: 5alpha-reduced metabolites formed, respectively. Most enzyme activities present at birth (i.e. 5beta-reductase, 5alpha-reductase, 17beta-hydroxysteroid reductase, 6beta- and 7alpha-hydroxylase) increased until 20 days of age in both male and female rats. Between 20 and 30 days of age a number of masculine metabolic characteristics appeared in both sexes, i.e. the 16alpha-hydroxylase and the 17alpha-hydroxysteroid reductase were induced, the 5beta-reductase activity rapidly increased and the 5alpha-reductase activity slightly decreased. During a third period beginning 30 days after birth the adult male enzyme activity pattern was completed by the induction of 3beta-hydroxysteroid reductase and a further increase in the activity of 16alpha-hydroxylase. After 30 days of age a feminine type of liver metabolism also rapidly developed in female rats; the 16alpha-hydroxylase and the 17alpha-hydroxysteroid reductase activities disappeared, the 6beta-hydroxylase and the 5beta-reductase activities decreased and the 5alpha-reductase activity increased six times. The developmental patterns of enzyme activities in the rat liver are consistent with a first developmental phase (0-30 days of age) independent of hypophysial control and probably determined primarily by the genome of the liver cell and a second phase (from 30 days onwards) with increasing sexual differentiation under hypophysial control. This control is mediated by some kind of feminizing factor in female rats and possibly by some kind of androgen-elicited secretion of masculinizing factor(s) in male rats. The metabolism of [4-14C]4-androstene-3, 17-dione was also studied during different times of the day and during different phases of the oestrous cycle. The 16alpha-hydroxylase activity showed a diurnal variation with higher values at noon than at midnight. The 5beta-reductase activity reached a maximal activity during metoestrus.