Sexual differences in hepatic metabolism and intracellular distribution of corticosterone studied by pulse labeling with (1,2,6,7-3H)corticosterone.

The subcellular distribution of corticosterone and its metabolites in liver was studied 5, 30, and 90 min after injection of (1,2,6,7-3/)corticosterone in adult male and female rats that were adrenalectomized or hypophysectomized: 5 min after administration of isotope, the adrenalectomized male rats contained ten times as much labeled unconjugated corticosterone, 5alpha-dihydrocorticosterone, and 3alpha- and 3beta,11beta,21-trihydroxy-5alpha-pregnan-20-one on the nuclear fraction than the corresponding female rats. The metabolites of corticosterone in the soluble fraction of liver from adrenalectomized females occurred as about 90 per cent steroid monosulfates and disulfates already 5 min after administration of isotope. In contrast, the soluble fraction of liver from males contained only 38 per cent labeled monosulfate 5 min after injection of (1,2,6,7-3H)corticosterone. The individual labeled metabolites from the different subcellular fractions were identified by thin-layer and radio-gas chromatography. The major metabolites found in the female were mono- and disulfurylated 3alpha,11beta,15,21-tetrahydroxy-5alpha-pregnan-20-one, 3alpha,15,21-trihydroxy-5alpha-pregnane-11,20-dione, and 3alpha,11beta,21-trihydroxy-5alpha-pregnan-20-one. The predominant metabolites in the male were 5alpha-pregnane-3alpha(and 3beta),11beta,20beta,21-tetrol and 3beta,11beta,21-trihydroxy-5alpha-pregnan-20-one which mainly occurred as mono- and disulfates. Hypophysectomized female rats showed a corticosterone metabolite pattern with almost no 15-hydroxylated metabolites but with large amounts of isomers of pregnane-3,11beta,20beta,21-tetrol, i.e., a "masculinized" pattern. It is concluded that hepatic intracellular metabolism and transport of corticosterone in vivo in rats are characterized by large sexual difference which are at least partly under hypophyseal control.