Steroid metabolism in rats given (1- 2 H 2 )ethanol. Biliary metabolites of corticosterone and administered 4-androstene-3,17-dione.

Abstract

The rate of excretion of different corticosterone metabolites in rat bile after administration of [1‐2H2]ethanol, and the transfer of deuterium to these metabolites have been studied by gas chromatography‐mass spectrometry. The excretion of corticosterone metabolites increased after injection of ethanol, but the relative amounts of different steroids remained essentially constant. The deuterium excess in 3α,11β, 15α,21‐tetrahydroxy‐5α‐pregnan‐20‐one and 3β(and 3α),11β,21‐trihydroxy‐5α‐pregnan‐20‐one in female rats and of 3β,11β,21‐trihydroxy‐5α‐pregnan‐20‐one, 5α‐pregnane‐3β‐(and 3α),11β,20β,21‐tetrol and 5β‐pregnane‐3α,11β,20β,21‐tetrol in male rats varied between 7 and 20 atoms per cent. Only monodeuterated molecules were found. All the deuterium in 3β,11β,21‐trihydroxy‐5α‐pregnan‐20‐one was present in the 3α‐position, and little or no deuterium was found in the 20α‐position of the corresponding 20β‐hydroxysteroid.When 4‐androstene‐3,17‐dione was given to male bile‐fistula rats, 3α‐hydroxy‐5α‐androstan‐17‐one, 3β‐hydroxy‐5α‐androstan‐17‐one, and 3α‐hydroxy‐5β‐androstan‐17‐one, and various hydroxylated metabolites were excreted in bile. Of the former compounds, the 3α,5β‐epimer was predominant in the glucuronide fraction, whereas the 3β,5α‐epimer was the major epimer in the sulphate fraction. During metabolism of [1‐2H2]ethanol the 3β‐ and 3α‐positions of these compounds contained 5–20 atoms per cent of deuterium. No deuterium was found in the 5α‐ or 5β‐positions.The results indicate that the coenzyme pool(s) used in different reductions at C‐3 is metabolically related to NADH formed in the alcohol dehydrogenase reaction. Since little or no deuterium was found at C‐5 and C‐20 other coenzyme pools are probably used for the reductions of these positions.