Sex differences in serum 7α-hydroxycholesterol levels in the rat reflect hepatic activity of 3β-hydroxy-Δ5-C27-steroid dehydrogenase and cholesterol 7α-hydroxylase

Factors that affect serum levels of 7α-hydroxycholesterol were studied in the rat. Serum levels of 7α-hydroxycholesterol differed in male and female rats fed regular chow (male; 0.2±0.1 nmol/ml (mean ±SD)n=8; female; 0.4±0.1 nmol/ml;n=8). When rats were fed with chow to which 3% cholestyramine had been added, the level increased significantly, particularly in female rats (male: 0.6±0.3 nmol/ml;n=8; female; 2.4±1.5 nmol/ml;n=8). The liver activity of cholesterol 7α-hydroxylase, the rate-limiting enzyme for degradation of cholesterol, did not show any sex differences, irrespective of whether the animals were fed with regular chow (male; 51±15 pmol/min per mg protein;n=8; female; 58±21 pmol/min per mg protein;n=8), or the cholestyramine-supplemented chow (male; 162±33pmol/min per mg protein;n=8; female; 172±33 pmol/min per mg protein;n=8). In contrast, the activity of 3β-hydroxy-Δ5-C27-steroid dehydrogenase, which acts after cholesterol 7α-hydroxylase in the catabolism of cholesterol, showed a marked difference between the sexes. In both sexes this enzyme activity was higher in cholestyramine-treated rats (male; 963±78 pmol/min per mg protein;n=8; female; 708±106 pmol/min per mg protein,n=8) compared to that in that rats received regular chow (male; 622±83pmol/min per mg protein;n=8). If the serum level of 7α-hydroxycholesterol depended solely on the enzyme activity of cholesterol 7α-hydroxylase, it would be difficult to explain these sex differences, since there were no sex differences in levels of cholesterol, 7α-hydroxylase. These results clearly indicate that, in the rat, the serum level of 7α-hydroxycholesterol depends not only on cholesterol 7α-hydroxylase activity but also on 3β-hydroxy-Δ5-C27-steroid dehydrogenase activity.