The circadian rhythm of synthesis and catabolism of cholesterol.

The circadian rhythms of HMG-CoA reductase and cholesterol-7 alpha-hydroxylase (low values, during light, rising in the evening with maximum at 12.00 p.m.) are investigated in rats under diverse conditions. Intragastral administration of cholestyramine (bile acid-absorbing resin) leads to an increased rhythm of both enzymes. Feeding of cholic acid (or cholesterol) reduces the activity of both enzymes (of HMG-CoA reductase and cholesterol-7 alpha-hydroxylase, respectively). In starved rats enzyme activity and time of day is proportional to the metabolism of a substrate.ies are lowered, too; a damped rhythm reappears after 24 h. A 20% fat diet (containing saturated fatty acids predominantly) markedly reduces the high values. Enzyme activities inhabited after thyroidectomy can be normalized by thyroxin substitution. Thyroxin administration in the normal remains without effect. Four-day insulin treatment of the normal inhibits cholesterol-7 alpha-hydroxylase, has no effect on HMG-CoA reductase. In the untreated diabetic rat cholesterol-7 alpha-hydroxylase is increased, HMG-CoA reductase significantly inhibited. Insulin treatment of the diabetic animal results in normalized values of HMG-CoA reductase whilst cholesterol-7 alpha-hydroxylase is nearly completely suppressed. The rate-limiting enzymes of cholesterol turnover are peripherally regulated by their products via a negative feedback. In contrast, hormones may have synergistic or opposite effects; thus they may represent means of higher regulation. All regulative possibilities discussed (except hypophysectomy) do modifiy the circadian rhythms. This cannot be demonstrated after hypophysectomy. After hypophysectomy circadian rhythms are not detectable any more. To get valid data about biochemical or pharmacological effects on these enzymes the circadian viriations have to be considered by measuring at different times of day (e.g. fat diet); for only the area of enzyme activit