ALTERED THYROID-HORMONE BINDING TO PLASMA-LIPOPROTEINS IN HYPOTHYROIDISM

Iodothyronine binding to plasma lipoproteins (Lp) and gel filtration e lution patterns of cholesterol and triglycerides were evaluated in the total lipoprotein fractions (TLF) obtained from 10 healthy blood dono rs and 7 patients with hypothyroidism of brief duration, TLF (d < 1.21 0 kg/L) shown to be free of plasma T-4 transport proteins (TBG, TTR, H SA) was equilibrated with 0.3 nM I-125-labeled T-4, T-3 or reverse T-3 (rT(3)) and chromatographed on Sepharose CL-6B. Percent distribution of rT(3) among the Lp subtypes was similar in the two groups (in norma ls: VLDL = 4.2 +/- 2.4, LDL = 15.6 +/- 4.2, HDL = 79.9 +/- 5.2) but HD L in hypothyroid subjects bound significantly more T-4 (98.7 +/- 0.4 v s. 91.2 +/- 0.3%) and 4 (95.5 +/- 2.6 vs. 78.3 +/- 11.3%). Correspondi ngly less T-4 and T-3 was bound to VLDL and LDL. Whereas rT(3) elution coincided with the major HDL cholesterol peak (202 +/- 17 kDa) and wa s the same in the two groups, both T-4 and T-3 eluted with smaller HDL particles and differed between hypothyroid and normal subjects. T-4 e luted with somewhat larger HDL particles in hypothyroid subjects (176 +/- 24 kDa vs. 111 +/- 34 kDa) and T-3 eluted with smaller HDL (94 +/- 30 kDa vs. 148 +/- 31 kDa). The major HDL-cholesterol peak in hypothy roid subjects had a slightly but significantly greater mass than in no rmals (241 +/- 28 kDa vs. 218 +/- 14 kDa). The HDL elution patterns al so differed: in normals there were from 3 to 6 minor peaks on either s ide of the major peak, whereas in hypothyroid subjects there were only 0 to 2 minor peaks. In conclusion, iodothyronines bind to relatively small size HDL subfractions and these are different for T-4, T-3, and rT(3); hypothyroidism of brief duration induces both quantitative and qualitative changes in iodothyronine distribution among lipoproteins a nd alters the microheterogeneity of HDL-cholesterol.