Hepatic cholesterol 7 alpha-hydroxylase activity and serum 7 alpha-hydroxy-cholesterol level during liver regeneration after partial hepatectomy in rats

Hepatic cholesterol 7 alpha-hydroxylase is a rate-limiting enzyme for bile acid synthesis, and we have previously shown that the serum 7 alpha-hydroxycholesterol level reflects the enzyme activity in patients with an intact liver. The purpose of this study was to evaluate the alterations in hepatic cholesterol 7 alpha-hydroxylase activity and the serum 7 alpha-hydroxycholesterol level after hepatectomy and the correlations between these parameters and liver mass. Hepatic cholesterol 7 alpha-hydroxylase activity, the serum 7 alpha-hydroxycholesterol level and the remaining liver weight were determined after 70% hepatectomy in rats. Cholesterol 7 alpha-hydroxylase activity was decreased on days 1 and 2 (from 28.3 +/- 3.7 to 8.5 +/- 2.8 and 13.3 +/- 3.6 pmol/min/mg protein, respectively), returned to the preoperative level on day 3 (24.7 +/- 2.6 pmol/min/mg protein) and further elevated thereafter (71.4 +/- 10.9 on day 7 and 51.3 +/- 6.6 pmol/min/mg protein on day 14). The serum level of 7 alpha-hydroxycholesterol changed simultaneously with the enzyme activity, and a significant correlation between the two parameters was observed (r = 0.915, p < 0.0001). The correlations between the liver weight and hepatic cholesterol 7 alpha-hydroxylase activity and serum 7 alpha-hydroxycholesterol level were significant (p < 0.01), but the significances disappeared for the period of days 3-14 (r = 0.424, p = 0.08; r = 0.299, p = 0.228, respectively). In conclusion, hepatic cholesterol 7 alpha-hydroxylase activity is suppressed by hepatectomy and then activated as the liver regenerates. The serum 7 alpha-hydroxycholesterol level is a good parameter of this enzyme activity after partial hepatectomy.