Rate of Cholesterol Synthesis in Hypo- And Hyperthyroid Rats

Abstract

Recently it was found in this laboratory that the hyperthyroid rat excretes far more cholesterol in his bile than the normal animal, whereas the hypothyroid rat has a considerably smaller daily output than the normal animal (1). This finding suggested that the rate of cholesterol synthesis was increased in the hyperthyroid and decreased in the hypothyroid state. Findings, however, such as the reciprocal relationship between thyroid activity and serum cholesterol level (2), the protection afforded by cholesterol against thyroid toxicity (3, 4), and the protective effect of thyroid against experimental atherosclerosis (5, 6) do not naturally lead to the thought that hyperthyroidism increases the rate of cholesterol synthesis. In the present study, tritium has been used to obtain data on the turnover rate of cholesterol in normal, hypo-and hyperthyroid animals. The results show a more rapid turnover in the hyperthyroid animal, and a slower turnover in the hypothyroid animal, as compared with normal controls. EXPERIMENTALData concerning the rate of cholesterol turnover were obtained on four groups of male rats of the Long-Evans strain. One group was fed powdered thyroid substance (0.3 per cent of the diet) for 14 days; at the time of the experiment these animals were 10 weeks old. A second group was fed thiouracil (0.3 per cent of the diet) for 98 days; at the time of the experiment this group was 20 weeks old. Two control groups of 9 week and 18 week old rats, respectively were fed stock diet. Dietary supplements administered as above have been shown (7,8) to induce hyperthyroidism and hypothyroidism, respectively, in rats. The activity, food consumption, weight changes, general condition, and behavior of our groups of rats confirmed this observation.The weight gain was largest in the control group and least in the hyperthyroid group. The rats receiving thiouracil had a retarded growth and decreased activity; those given thyroid substance exhibited hyperactivity, marked tremor, tachycardia, and polyphagia.

Estimation of the Phospholipid Phosphorus Turnover Time in Man: Studies in Normal Individuals, in Patients With the Nephrotic Syndrome and in Other Types of Hyperlipemia 1

“…This finding is in agreement with results obtained in experimental animals by Flock, Bollman, and Berkson (12) and data on cholesterol synthesis in hypo-and hyperthyroid rats by Byers, Rosenman, Friedman, and Biggs (26). Since our studies in hypothyroidism are confined to one patient they are not suitable for statistical analysis.…”

Hypothyroidism Modifies Lipid Composition of Polymorphonuclear Leukocytes

“…Hypothyroidism also provoked a significant decrease of the serum TG concentration. The inverse correlation between serum TC and thyroid hormone levels has been known from experimental observations which date back to over 70 years [38]. Hypothyroidismassociated hypercholesterolemia would mainly be due to a decreased rate of receptor-mediated catabolism of the plasmatic lipoproteins in the liver.…”

A Possible Explanation of Myxedema and Hypercholesterolemia in Hypothyroidism: Control of Lysosomal Hyaluronidase and Cholesterol Esterase by Thyroid Hormones

“…Hypthyroid humans and animals tend to have increased serum cholesterol levels (5,6), even though cholesterol synthesis is significantly lower in the hypothyroid state (11)(12)(13)(14). Therefore, cholesterol degradation must also be reduced in hypothyroidism, and this effect appears to be the primary cause of the elevated serum cholesterol levels.…”

“…On the other hand, hyper thyroid rats and patients tend to have decreased serum cholesterol levels. Since cholesterol synthesis actually increases in hy perthyroidism (11,12,14), enhanced degra dation or elimination of cholesterol must be the important factor in determining serum levels. In fact, accelerated cholesterol degra dation in hyperthyroidism has been demon strated (11,15,16), although the biochemical basis for this increased breakdown has not been elucidated.…”