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Sex and substrate effects on hepatic corticosteroid metabolism in the rat.

Liver homogenates from male rats metabolized cortisol, cortisone, and 11-deoxycortisol by reduction at the α-ketol sidechain and the A-ring in equal amounts; with the native steroids, corticosterone, and 11-deoxycorticosterone, however, reduction at the A-ring far exceeded that at the sidechain. Liver homogenates from female rats metabolized all substrates tested more efficiently at the A-ring than at the sidechain. Females cleared corticosterone from plasma more rapidly and cortisol less rapidly than males. Corticosterone was cleared more rapidly than cortisol in both sexes. Orchiectomy shortened the half-life of corticosterone without affecting that of cortisol. Both male and female hamsters reduced more corticosterone than cortisol at the A-ring in vitro; nonetheless, in vivo metabolism of cortisol was more rapid than corticosterone in both sexes. The sex difference in corticosterone metabolism was similar to that for cortisol in hamsters, males metabolizing both more rapidly than females. The divergen...