Differences between Germ-free and Conventional Rats in Liver Microsomal Metabolism of Steroids

Abstract

Abstract The metabolism of some steroids has been investigated in liver microsomal preparations from male germ-free and conventional rats. Hydroxylation of 4-[4-14C]androstene-3,17-dione in positions 6β and 16α is about 2 and 1.5 times more efficient in germ-free than in conventional rats. The same is true for 6β- and 2α-hydroxylation of 4-[4-14C]pregnene-3,20-dione (about 1.6 and 1.2 times larger, respectively, in germ-free animals), for 18-hydroxylation of 5α-[4-14C]-androstane-3α,17β-diol (about 1.6 times larger in germ-free rats), and for 6β-hydroxylation of lithocholic acid (about 2 times larger in germ-free rats). All these differences are statistically significant (significance level, p l 0.05). Similar differences (although not statistically significant) are also found for 16α-hydroxylation of 4-pregnene-3,20-dione and for 2β- and 2α-hydroxylation of 5α-androstane-3α,17β-diol. The amount of cytochrome P-450 in germ-free animals is 2.53 ± 0.45 nmoles per mg of protein as compared to 1.72 ± 0.04 nmoles per mg of protein in conventional animals (p l 0.005). 5α-Reduction of 4-androstene-3,17-dione, 4-pregnene-3,20-dione and of 7α-[6β-3H]hydroxy-4-cholesten-3-one tends to be lower in germ-free than in conventional rats. In contrast to these results, 12α-hydroxylation of 7α-hydroxy-4-cholesten-3-one and 7α-hydroxylation of [4-14C]-cholesterol are larger in conventional than in germ-free rats. These findings are in accordance with the slower cholesterol and bile acid turnover in germ-free compared to conventional rats.