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

Jan Carlstedt-Duke, Jan Åke Gustafsson, Sven A. Gustafsson

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)639-648
Number of pages10
JournalBiochemistry
Volume14
Issue number3
DOIs
StatePublished - Feb 1 1975

ASJC Scopus subject areas

  • Biochemistry

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