Abstract
The present studies were undertaken to investigate the influence of thyroid function on the metabolism of fatty acid and cholesterol in rats using acetate- 1 -14C and palmitate-1-14C. It was also thought of interest to ascertain whether thyroid stimulating hormone (TSH) affects lipid metabolism not only in the intact animal but also in the absence of the thyroid gland. Male rats of the Wistar strain weighing 140 to 150 gm were divided into 7 groups : hypophysectomized rats (operated 3 days prior to sacrifice), thyroidectomized rats (operated 7 days prior to sacrifice), intact rats given 30 μg of L-thyroxine per 100 gm of body weight daily for 5 days, thyroidectomized rats given 2.5 μg of L-thyroxine per 100 gm of body weight daily for 5 days, intact rats given 0.2 U.S.P.U. of TSH (Thytropar) daily for 7 days, thyroidectomized rats given 0.2 U.S.P.U. of TSH daily for 7 days and nontreated control. Each was then injected intraperitoneally with acetate- 1 14C (5 μc per 100 gm of body weight) or palmitate-1-14C (1 μc per 100 gm of body weight). Following the administration of the isotope, liver, epididymal adipose tissue and blood samples were obtained at 0.25, 0.5, 1, 2, 6 and 24 hours. For the separation of fatty acids and cholesterol of tissues and plasma the method of Srere et al was used, and the cholesterol concentration was determined by the method of Abell et al. Radioactivities of these fractions were measured by a gas flow counter. Specific activity was expressed as cpm per mg of each fraction after correction for self-absorption.
1) Thyroidectomy resulted in an increase in the concentration of liver and plasma cholesterol, and L-thyroxine administration to thyroidectomized rats brought back this increase approximately to normal, whearas L-thyroxine administration to normal rats had no effect on the liyer and plasma cholesterol concentration. However, the concentration of cholesterol in epididymal adipose tissue was elevated by L-thyroxine treatment. The difference in cholesterol concentration in all these tissues between thyroidectomized rats and thyroidectomized rats given TSH was not significant.
2) In normal rats, the maximum acetate-1-14C incorporation for liver cholesterol and that for liver fatty acids occurred at 1 and 2 hours, respectively.
3) The specific activity of liver cholesterol 15 minutes after acetate-1-14C injection was much higher in intact rats given L-thyroxine than in nontreated control, while that 6 hours after injection was lower in the former than in the latter. Furthermore, in the thyroidectomized group the initial incorporation of acetate-1-14C into liver cholesterol was lower than nontreated control and this was restored by L-thyroxine administration, while the specific activity of liver cholesterol 24 hours after injection in the thyroidectomized group remained consistently high. These results demonstrate that thyroid hormone accelerates biosynthesis as well as degradation of cholesterol in the liver. Consequently, the increased concentration of plasma cholesterol observed in the hypothyroid state is probably explained by the differences in degree of the alteration of synthesis and elimination or destruction of cholesterol, i.e. the more marked decrease in the rate of elimination. It was also observed that hepatic cholesterogenesis was greatly reduced in hypophysectomized rats.
4) The administration of L-thyroxine, 30 μg per 100 gm of body weight daily for 5 days to produce hyperthyroidism, increased the initial incorporation of acetate-1-14C into liver fatty acids. Conversely, thyroidectomy resulted in a decrease in the hepatic lipogenesis. This impaired hepatic lipogenesis found in thyroidectomized rats, however, was not restored by L-thyroxine administration.
