Hydrolase activities in the rat aorta. V. Comparison to activities in liver and kidney after thyroidectomy and relation to dynamic clearance of circulating low density lipoproteins.

Abstract

Thyroid hormones influence circulating low density lipoprotein (LDL) levels in humans; they could have an effect on LDL catabolism. Male rats were thyroidectomized (H); half were treated for 7 days with 2 micrograms triiodothyronine/100 g body weight (T) and both groups were compared to controls (C). Aorta, liver, and kidney were assayed for cellular marker enzymes, including lysosomal acid cholesteryl esterase (ACE). Specific activities of ACE (mU/mg DNA; mean +/- SD) were: Aorta, C, 0.19 +/- 0.01; H, 0.16 +/- 0.01; T, 0.21 +/- 0.01; Liver: C, 15.55 +/- 1.49; H, 9.16 +/- 1.54; T, 15.43 +/- 2.28; Kidney: C, 1.70 +/- 0.23; H, 1.04 +/- 0.13; T, 2.08 +/- 0.35. Half lives for injected unmodified 125I-labeled human LDL were 11.5 +/- 0.7 hour in C, 16.2 +/- 3.1 in H, and 12.9 +/- 0.9 in T groups. Fractional catabolic rates (FCR) of LDL in %/hr were 6.5 +/- 0.6 in C; 4.8 +/- 0.5 in H, and 6.0 +/- 0.3 in T. Reductively methylated 125I-labeled human LDL had half-lives of 14.9 +/0 1.4 hour in C and 15.1 +/- 1.6 hour in H and the FCR of this modified LDL was 5.3 +/- 0.5 %/hr in C and 5.2 +/- 0.7 %/hr in H groups. Thus, thyroidectomy results in marked decreases in ACE specific activity of liver and kidney and a marked decrease in FCR and prolonged half-life of non-modified LDL (all P less than 0.05). On the other hand, methylated LDL showed a similarly reduced FCR and prolonged half-life in control and thyroidectomized rats (P less than 0.05). This suggests a major effect of thyroid deficiency on receptor-mediated uptake of LDL in vivo and demonstrates the influence of hormonal status on dynamic clearance and catabolism of LDL.