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A mixture of testosterone-4-14C and testosterone-1,2-3H-17-glucosiduronate was intraperitoneally administered into male and female rats with bile fistulas. Biliary metabolites were separated and purififd by a combination of column chromatography, enzymic hydrolysis or solvolysis of the conjugate fractions and identification of the liberated aglycones. The injected steroids were extensively metabolized and excreted predominantly in the blue. 5β-Androstane-3α, 17β-diol was found principally in monoglucosiduronate fraction and was produced preferentially from the injected conjugate in both sexes. Very marked sex differences from the injected conjugate in both sexes. Very marked sex differences were observed in the following metabolites: Androsterone was present only in the female as monoglucosidironate, which was preferentially derived from testosterone. 5α-Androstane-3α,17β-diol was identified in both monoglucosiduronate and diconjugate fractions of the female, which was formed significanrly more from the conjugate than testosterone. These findings provide evidence that testosterone glucosiduronate could be converted directly into 5α-steroids as well as 5β-ones in vivo . In marked contrast, the major portion of testosterone was metabolized to polar steroids in the male.

The fate of 4- 14 C-testosterone 17-N-acetyl-glucosaminide has been studied in two subjects. Following intravenous administration urinary excretion of radioactivity was rapid. Testosterone N-acetylglucosaminide was the principal metabolites; etiocholanolone and androsterone conjugated with glucuronic acid were present in a ratio of 7.3. Following oral administration only traces of metabolites conjugated with the aminosugar were present. Etiocholanolone and androsterone were obtained in ratio of 7.3. In both studies etiocholane-3α,17β-diol was the predominant non-ketonic metabolite. These results were compared with the metabolites obtained following labelled testosterone and testosterone 17-glucosiduronate. The results demonstrate that 1) the cleavage of the glycosidic linkage is almost complete by the oral route, 2) ring A is reduced prior to hydrolysis of the aminosugar and 3) there is a directive influence of the aminosugar toward 5β-reduction similar to that of a glucosiduronate group at C-17.