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Binding of Thyroid Hormones to Human Plasma Lipoproteins^*

SALVATORE BENVENGA, RICHARD E. GREGG and JACOB ROBBINS

Clinical Endocrinology Branch, National Institute of Diabetes, Digestive and Kidney Diseases (S.B., J.R.), and Molecular Disease Branch, National Heart, Lung, and Blood Institute (R.E.G.), National Institutes of Health Bethesda, Maryland 20892

Address requests for reprints to: Dr. Jacob Robbins, Building 10, Room 8N315, National Institutes of Health, Bethesda, Maryland 20892.

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

^* Presented in part at the Annual Meeting of the European Thyroid Association, Stockholm, Sweden, June 29-July 4,1986.

On leave of absence from the Istituto Pluridisciplinare di Clinica Medica e Terapia Medica Generale e Speciale, Thyroid Unit, University of Messina, School of Medicine, 98100 Messina, Italy. Supported by grant from Boncompagni-Ludovisi Stiftelsen Foundation, Stockholm, Sweden.

Received August 14, 1987.

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