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1. Sexual differentiation of the metabolism of testosterone in liver slices of normally developed, sexually mature mice: Sexual differentiation in the mouse, unlike that in the rat, shows a high degree of uniformity: Where the formation of metabolites with the composition C19O2 is markedly greater in one sex, then this is invariably the male. The formation of C19O3 steroids and 4-androstene-3,17-dione, and the turnover of testosterone show no marked sexual differences, although the sum of the C19O2-type delta4-hydrogenation products of testosterone is significantly greater in the male. This apparent discrepancy is explained by the fact that the sum of the delta4-hydrogenation products represents no more than 10% of testosterone turnover. Thus, sexual differences in the formation of individual delta4-hydrogenation products are not apparent from a consideration of the overall turnover of testosterone. 2. Sexual differentiation of testosterone metabolism studied in genetically male litter mates, carrying the X-chromosome-bound mutation and showing testicular feminization (Tfm): The Tfm mutation (genotype XTfm Blo/Y; Blo = coat colour gene Blotchy) results in a feminization of testosterone metabolism. Where the level of testosterone metabolites is significantly higher in the normal male than in the normal female, the Tfm mutation shows a level that is significantly lower than in the normal male, and which, in most cases, is the same as that in the normal female. The concentration of three metabolites (3alpha- and 3beta-hydroxy-5beta-androstan-17-one, and 5beta-androstane-3,17-dione), which do not show sex-based differences, were significantly increased in the Tfm mutation. The Tfm mutation therefore effects the formation of all ring A hydrogenation products of type C19O2 (with the single exception of 5bets-androstane-3alpha,17beta-diol). It does more than simply equalize sexual differences by feminization. It has no effect on the hydroxylation of testosterone, or on its 17beta-dehydrogenation to 4-androstene-3,17-dione. The consequences of the Tfm mutation for the liver are irreversible: The formation of 5alpha-androstane-3,17-dione, which is a representative parameter for the sexual differentiation of testosterone metabolism, is not influenced by the injection of testosterone (15 mg i.p. 6 days before investigation).

hoppe-seyler's zeitschrift für physiologische chemie

Der sexuell differenzierte Stoffwechsel von Testosteron in Leberschnitten der Maus und seine Alteration durch eine zur testikulären Feminisierung führende X-Chromosomgebundene Mutation