Altered thyroid hormone binding to plasma lipoproteins in hypothyroidism

Iodothyronine binding to plasma lipoproteins (Lp) and gel filtration elution patterns of cholesterol and triglycerides were evaluated in the total lipoprotein fractions (TLF) obtained from 10 healthy blood donors and 7 patients with hypothyroidism of brief duration. TLF (d < 1.210 kg/L) shown to be free of plasma T4 transport proteins (TBG, TTR, HSA) was equilibrated with 0.3 nM 125I-labeled T4, T3 or reverse T3 (rT3) and chromatographed on Sepharose CL-6B. Percent distribution of rT3 among the Lp subtypes was similar in the two groups (in normals: VLDL = 4.2 +/- 2.4, LDL = 15.6 +/- 4.2, HDL = 79.9 +/- 5.2) but HDL in hypothyroid subjects bound significantly more T4 (98.7 +/- 0.4 vs. 91.2 +/- 0.3%) and T3 (95.5 +/- 2.6 vs. 78.3 +/- 11.3%). Correspondingly less T4 and T3 was bound to VLDL and LDL. Whereas rT3 elution coincided with the major HDL cholesterol peak (202 +/- 17 kDa) and was the same in the two groups, both T4 and T3 eluted with smaller HDL particles and differed between hypothyroid and normal subjects. T4 eluted with somewhat larger HDL particles in hypothyroid subjects (176 +/- 24 kDa vs. 111 +/- 34 kDa) and T3 eluted with smaller HDL (94 +/- 30 kDa vs. 148 +/- 31 kDa). The major HDL-cholesterol peak in hypothyroid subjects had a slightly but significantly greater mass than in normals (241 +/- 28 kDa vs. 218 +/- 14 kDa). The HDL elution patterns also differed: in normals there were from 3 to 6 minor peaks on either side 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 T4, T3, and rT3; hypothyroidism of brief duration induces both quantitative and qualitative changes in iodothyronine distribution among lipoproteins and alters the microheterogeneity of HDL-cholesterol.