EFFECT OF COMPOUNDS RELATED TO THYROXINE ON SERUM AND LIVER CHOLESTEROL AND ON ATHEROSCLEROSIS AND HEART WEIGHTS IN RATS AND MICE

Abstract

SUMMARY 1. Methods are described for comparing the activity of compounds related to thyroxine in controlling the increases in cholesterol concentration in the serum and in the liver, and the increased sudanophilia in the cardiovascular system, after feeding diets containing cholesterol, choline, fat and cholic acid. 2. The three test procedures described placed the compounds tested in a similar order of activity. Little activity could be detected in compounds not containing an iodine atom at both the 3 and 5 positions in the molecule. Compounds with iodine atoms at the 3:5:3′ positions were more active than those substituted at the 3:5:3′:5′ positions, which in turn were more active than the 3:5 di-substituted compounds. The l isomers of 3:5:3′-triiodo-thyronine and thyroxine were more active than the d isomers, but 3:5-diiodo-d-thyronine was as active as 3:5-diiodo-l-thyronine. 3. Methods are also described for comparing the activity of the same compounds in causing ventricular enlargement in mice maintained on a stock diet and in rats maintained on a diet containing added fat, cholesterol, choline and cholic acid or on a stock diet with added thiouracil. 4. The tests involving ventricular hypertrophy placed all the compounds tested in approximately the same order of activity, broadly similar to that shown in published results obtained by the oxygen consumption rate or antigoitrogenic tests. Little, if any, activity could be detected except in compounds with iodine atoms at both the 3 and 5 positions in the molecule. Compounds with iodine atoms at the 3:5:3′ positions were more active than the corresponding compounds with iodine atoms at the 3:5:3′:5′ positions, which in turn were more active than the 3:5 di-substituted products. Iodinated l-thyronine derivatives were more active than the corresponding thyroacetic acid compounds, which in turn were more active than the thyroformic acid derivatives. Iodinated l-thyronine derivatives were more active than the d-isomers. 5. The ratio of the activity of a compound in preventing elevation of serum cholesterol to its effect on the heart was about three times as great for some, such as 3:5-diiodo-d-thyronine and d-thyroxine, as for others, such as 3:5:3′-triiodo-l-thyronine and l-thyroxine.