THE 5β-METABOLITES OF TESTOSTERONE: MODE AND SEX-SPECIFICITY OF THEIR FORMATION IN THE RAT LIVER

Abstract

ABSTRACT Rat liver slices provide a suitable test model which, with simple and variable experimental conditions, contributes direct evidence for the formation of the 5β-metabolites, 17β-hydroxy-5β-androstan-3-one, 5β-androstane-3α,17β-diol and 3α-hydroxy-5β-androstan-17-one, from a direct hydrogenation of testosterone glucuronide. When liver slices are incubated with testosterone in a KHR-phosphate medium no glucuronidation occurs and no 5β-metabolites are formed. They are produced, however, in a KHR-hydrogencarbonate medium, in which the slices are able to form glucuronides. Moreover, the production rate of 5β-hydrogenated products like that of testosterone glucuronide formation is sex-specific. The male animal metabolizes less testosterone by oxidoreductive pathways than the female and thus exhibits the higher testosterone glucuronide formation. This higher glucuronide formation rate is closely associated with the appearance of 5β-metabolites in the aglucone fraction. Apparently, the testosterone glucuronide formation rate of the female animal is not sufficiently high to allow the production of 5β-configurated C19O2-aglucones in measurable quantities. An experimentally induced feminization of the hepatic metabolism of genetically male rats by a single injection of 300 μg oestradiol benzoate on day 2 of life reduces the testosterone glucuronide formation rate to the female level and causes the 5β-metabolites to disappear. Thus, it is evident that at least those 5β-metabolites mentioned above are products of a direct hydrogenation of testosterone glucuronide.