HDL clearance and receptor-mediated catabolism of LDL are reduced in hypothyroid rats.

Hypercholesterolemia associated with hypothyroidism is due partly to increased plasma LDL and partly to increased HDL cholesterol concentrations. The increase in LDL cholesterol has been shown to be secondary to reduced plasma clearance of LDL. To determine which catabolic route was thyroid dependent, the present study examined the effects of hypothyroidism on the receptor-mediated pathway and the 'receptor-independent' pathway of LDL metabolism. Wistar rats (327 +/- 22 g; mean +/- SD) were made hypothyroid by feeding propylthiouracil (0.1%, w/w) and rat 131I-LDL (rLDL; d = 1.019-1.050) and 125I-methylated-LDL (rLDL-CH3) were simultaneously injected i.v. after which the rates of clearance of labelled LDL in plasma were determined over 0-54 h. Total LDL and 'receptor-independent' clearances were represented by clearance of 131I-rLDL and 125I-rLDL-CH3 respectively and the difference between the two represented high affinity receptor-mediated clearance. The data were analyzed using Matthews' model and the fractional catabolic rates (FCR) were calculated. The FCR of rLDL clearance via the receptor-mediated pathway was 0.1042 +/- 0.0112 pools/h (n = 6) in controls vs. 0.0613 +/- 0.0079 pools/h (n = 6) in hypothyroid animals (P less than 0.01). The FCR via the 'receptor-independent' pathway was 0.0642 +/- 0.0040 pools/h (n = 6) in controls vs. 0.0561 +/- 0.0036 pools/h (n = 6) in hypothyroid animals (not significant). The plasma HDL cholesterol concentration was also increased in hypothyroid rats (70.4 +/- 6.7 mg/dl) compared to control (53.3 +/- 3.1 mg/dl) (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)