Differences between germ-free and conventional rats in liver microsomal metabolism of steroids.

The metabolism of some steroids has been investigated in liver microsomal preparations from male germ-free and conventional rats. Hydroxylation of 4-[4-14C]androstene3,17-dione in positions 60 and 16~~ is about 2 and 1.5 times more efficient in germ-free than in conventional rats. The same is true for 6/3and Zol-hydroxylation of 4-[4J4C]pregnene-3,20-dione (about 1.6 and 1.2 times larger, respectively, in germ-free animals), for 1%hydroxylation of 5a-[4J4C]androstane-3a, 17P-diol (about 1.6 times larger in germ-free rats), and for 6P-hydroxylation of lithocholic acid (about 2 times larger in germ-free rats). All these differences are statistically significant (significance level, p < 0.05). Similar differences (although not statistically significant) are also found for 16or-hydroxylation of 4-pregnene-3,20-dione and for 2/3and 2a-hydroxylation of Sac-androstane-30c, 17pdiol. The amount of cytochrome P-450 in germ-free animals is 2.53 f 0.45 nmoles per mg of protein as compared to 1.72 i 0.04 nmoles per mg of protein in conventional animals (p < 0.005). %-Reduction of 4-androstene-3,17-dione, 4-pregnene-3,20-dione and of 7~[6/3-~H]hydroxy-4-cholesten-3.one tends to be lower in germ-free than in conventional rats. In contrast to these results, 12cz-hydroxylation of 7~ hydroxy-4-cholesten-3-one and 7or-hydroxylation of [4J4C]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.