Metabolism of 11-oxygenated steroids. 1. Influence of the A/B ring junction on the reduction of 11-oxo groups

Abstract

An earlier hypothesis that reduction of steroid 11-oxo-to 11[beta]-hydroxy groups in vivo was largely dependent on the stereochemistry of the A and B rings has been tested by studying the metabolism of various 3[alpha]-hydroxy steroids. 11-Oxoandrosterone, 11[beta]-hydroxy-androsterone, 11-oxoetiocholanolone, 11[beta]-hydroxyetiocholanolone, tetra-hydrocortisone and allotetrahydrocortisone were given by mouth in doses of 40 to 100 mg to young male volunteers, together with prednisone or prednisolone to suppress endogenous adrenocortical secretion. Steroids in blood plasma and urine were estimated and identified by chromatographic methods. The proportions of the major metabolites of 11-oxoandrosterone (5[alpha]-H) and of allotetrahydrocortisone (5[alpha]-H) the 11[beta]-hydroxy (reduced) form were 23 and 91% respectively. No 11[beta]-hydroxy metabolites of the other steroid precursors (5B-H) were detected (<2% of their major metabolites). The C21 3[alpha]-hydroxy steroids gave rise to small but significant amounts of the related 17-oxosteroids and 20 [xi] -hydroxy steroids. It is suggested that the normal pattern of 11-oxo and 11[beta]-hydroxy steroids in human urine, in which little or no 11-oxo-5[alpha]-(H) steroids can be found while the 11-oxo- 5[beta]-(H) metabolites are more plentiful than 11[beta]-hydroxy-5[beta](H) metabolites, is largely accounted for by the ease with which the 11-oxo-5[alpha]-(H) metabolites are reduced to the related 11[beta]-alcohols.