Sexual Differences in Hepatic Metabolism and Intracellular Distribution of Corticosterone Studied by Pulse Labeling with Corticosterone-1,2,6,7-³H

The subcellular distribution of corticosterone and its metabolites in liver was studied 5, 30, and 90 min after injection of [1,2,6,7-³H]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, 5α-dihydrocorticosterone, and 3α- and 3β,11β,21-trihydroxy-5α-pregnan-20-one in 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% steroid monosulfates and disulfates already 5 min after administration of isotope. In contrast, the soluble fraction of liver from males contained only 38% 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 3α,11β,15,21-tetrahydroxy-5α-pregnan-20-one, 3α,15,21-trihydroxy-5α-pregnane-11,20-dione, and 3α,11β,21-trihydroxy-5α-pregnan-20-one. The predominant metabolites in the male were 5α-pregnane-3α(and 3β), 11β,20β,21-tetrol and 3β,11β,21-trihydroxy-5α-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-3,11β,20β,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 differences which are at least partly under hypophyseal control.