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

Abstract

Factors that affect serum levels of 7 alpha-hydroxycholesterol were studied in the rat. Serum levels of 7 alpha-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 7 alpha-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 +/- 33 pmol/min per mg protein; n = 8; female; 172 +/- 33 pmol/min per mg protein; n = 8). In contrast, the activity of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, which acts after cholesterol 7 alpha-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 +/- 83 pmol/min per mg protein; n = 8; female; 469 +/- 41 pmol/min per mg protein; n = 8). If the serum level of 7 alpha-hydroxycholesterol depended solely on the enzyme activity of cholesterol 7 alpha-hydroxylase, it would be difficult to explain these sex differences, since there were no sex differences in levels of cholesterol 7 alpha-hydroxylase. These results clearly indicate that, in the rat, the serum level of 7 alpha-hydroxycholesterol depends not only on cholesterol 7 alpha-hydroxylase activity but also on 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase activity.