SEX-DIFFERENCES IN SERUM 7-ALPHA-HYDROXYCHOLESTEROL LEVELS IN THE RATREFLECT HEPATIC ACTIVITY OF 3-BETA-HYDROXY-DELTA(5)-C-27-STEROID DEHYDROGENASE AND CHOLESTEROL 7-ALPHA-HYDROXYLASE

Factors that affect serum levels of 7 alpha-hydroxycholesterol were st udied 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 (m ean +/- SD): n = 8; female; 0.4 +/- 0.1 nmol/ml; n = 8). When rats wer e fed with chow to which 3% cholestyramine had been added, the level i ncreased 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 activi ty of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for de gradation of cholesterol, did not show any sex differences, irrespecti ve 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 prot ein; n = 8), or the cholestyramine-supplemented chow (male 162 +/- 33 pmol/min per mg protein: n = 8; female; 172 +/- 33 pmol/min per mg pro tein; n = 8). In contrast. the activity of 3 beta-hydroxy-Delta(5)-C-2 7-steroid dehydrogenase, which acts after cholesterol 7 alpha-hydroxyl ase in the catabolism of cholesterol, showed a marked difference betwe en the sexes. In both sexes this enzyme activity was higher in cholest yramine-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 p rotein: n = 8: female: 469 +/- 41 pmol/min per mg protein; n = 8), If the serum level of 7 alpha-hydroxycholesterol depended solely on the e nzyme activity of cholesterol 7 alpha-hydroxylase, it would be difficu lt to explain these sex differences, since there were no sex differenc es in levels of cholesterol 7 alpha-hydroxylase. These results clearly indicate that, in the rat, the serum level of 7 alpha-hydroxycholeste rol depends not only on cholesterol 7 alpha-hydroxylase activity but a lso on 3 beta-hydroxy-Delta(5)-C-27-steroid dehydrogenase activity.