Binding of Thyroid Hormones to Human Plasma Lipoproteins*

Abstract

The binding of T₄, T₃, and rT₃ to plasma lipoproteins was investigated in normal subjects and patients with abnormal lipoprotein metabolism. Gel filtration on Sepharose CL-6B demonstrated iodothyronine binding to all lipoprotein classes. In the total lipoprotein fraction (density < 1.210 g/mL), high density lipoproteins (HDL) were the major binders, accounting for 92% of lipoprotein-bound T₄, 99% of lipoproteinbound T₃, and 55% of lipoprotein-bound rT₃. The estimated iodothyronine binding in normal plasma to HDL, low density lipoproteins (LDL), and very low density lipoproteins (VLDL) was 3%, 0.2%, and 0.03% for T₄, 6%, 0.05%, and 0.02% for T₃, and 0.1%, 0.1%, and 0.01% for rT₃, respectively. These estimates may be low owing to possible dissociation during chromatography and the short incubation period used to avoid changes in lipoprotein structure. In VLDL and LDL deficiency (abetalipoproteinemia), HDL deficiency (Tangier disease), LDL excess (type Ha hyperlipoproteinemia), and VLDL excess (type III, IV, and V hyperlipoproteinemia), the distribution of iodothyronines reflected the lipoprotein abnormality. Variations resulting from altered distribution within HDL subclasses were also found. Binding was saturable, with approximate dissociation constants for VLDL, LDL, and HDL of lO⁻⁵–lO⁻⁶ mol/L. We conclude that thyroid hormones bind specifically to apolipoproteins, although additional binding by solubilization in the lipid components of the lipoproteins may also occur