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]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 < 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 < 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.