3-Iodothyronamine (T 1 AM) is a biogenic amine derivative of thyroid hormone present in tissue and blood of vertebrates. Approximately 99% of the circulating thyroid hormones are bound to plasma proteins, including three major thyroid hormone-binding proteins, and the question arises as to whether circulating T 1 AM is also bound to serum factors. We report here that T 1 AM is largely bound to a single protein component of human serum. Using T 1 AM-affinity chromatography, we isolated this protein, and sequence analysis identified it as apolipoprotein B-100 (apoB-100), the protein component of several low density lipoprotein particles. Consistent with this finding, we demonstrate that >90% of specifically bound T 1 AM in human serum resides in the apoB-100-containing low density lipoprotein fraction. T 1 AM reversibly binds to apoB-100-containing lipoprotein particles with an equilibrium dissociation constant (K D ) of 17 nM and a T 1 AM/apoB-100 stoichiometry of 1:1. Competition binding assays demonstrate that this binding site is highly selective for T 1 AM. Intracellular T 1 AM uptake is significantly enhanced by apoB-100-containing lipoprotein particles. Modest enhancements to apoB-100 cellular uptake and secretion by T 1 AM were observed; however, multidose T 1 AM treatment did not affect lipid or lipoprotein inventory in vivo. Thus, it appears that apoB-100 serves as a carrier of circulating T 1 AM and affords a novel mechanism by which T 1 AM gains entry to cells.

TA4 may be ubiquitously generated in many tissues and enhances the biological impact of thyrotropin and thyroid-stimulating immunoglobulins in orbital connective tissue. These findings may identify a physiologically important determinant of extrathyroidal thyroid-stimulating hormone action.