Abstract
Partition of T4 to plasma proteins is classically attributed only to TBGC ≈70%), transthyretin (≈15%) and albumin (≈10%), based on zone electrophoresis. Since TBG migration spans the α1 and α2 regions, and since HDL, which have α1 migration, transport ≈4% of circulating T4, other α-globulins could bind T4 and “contaminate” the TBG area. Hence, we determined the association of [125I]T4 to TBG and, for comparison, to transthyretin and albumin. Sera from 50 normolipidemic individuals were equilibrated with [125I] T4 and analyzed by both zone electrophoresis and radioimmunoprecipitation with specific antisera. Transthyretin-T4 or albumin-T4 bindings as assessed by the two methods agreed, while TBG-T4 did not, because other α-globulins carrying T4 with low affinity co-migrated with TBG. Some, but not all, of these α-globulins belong to the same superfamily of TBG and also bind steroid hormones.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Robbins J. Thyroid hormone transport proteins and the physiology of hormone binding. In: Braverman L.E., Utiger R.D. (Eds.), Werner and Ingbar’s The thyroid, a fundamental and clinical text. Lippincott Williams & Wilkins, Philadelphia, 2000, p. 105.
Benvenga S., Gregg R.E., Robbins J. Binding of thyroid hormones to human plasma lipoproteins. J. Clin. Endocrinol. Metab. 1988, 67: 6–16.
Benvenga S., Lapa D., Trimarchi F. Re-evaluation of the thyroxine binding to human plasma lipoproteins using three techniques. J. Endocrinol. Invest. 2001, 24: RC 16–18.
Flink I.L., Bailey T.H., Gustafson T.A., Markham B.E., Markin E. Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases. Proc. Natl. Acad. Sci. USA 1986, 83: 7708–7712.
Hammond G.L., Smith C.L., Goping I.S., Underhill D.A., Harley M.J., Reventos J., Musto N.A., Gunsalus G.L., Bardin C.W. Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exibits homology with serine protease inhibitors. Proc. Natl. Acad. Sci. USA 1987, 84: 5153–5157.
Benvenga S., Bartolone L., Squadrito S., Trimarchi F. Thyroid hormone autoantibodies elicited by diagnostic fine needle biopsy. J. Clin. Endocrinol. Metab. 1997, 82: 4217–4223.
Benvenga S., Cahnmann H.J., Robbins J. Characterization of the binding of thyroxine to apolipoprotein E: localization of the binding site in the exon 3-coded domain. Endocrinology 1993, 133: 1300–1305.
Benvenga S., Cahnmann H.J., Robbins J. Characterization of the binding of thyroxine to high density lipoproteins and apolipoprotein A-I. J. Clin. Endocrinol. Metab. 1989, 68: 1067–1070.
Benvenga S., Cahnmann H.J., Rader D., Kindt M., Robbins J. Thyroxine binding to the apolipoproteins of high density lipoproteins HDL2 and HDL3. Endocrinology 1992, 131: 2805–2811.
Goncalves E., Lakshmanan M., Cahnmann H.J., Robbins J. High-affinity binding of thyroid hormones to neuroblastoma plasma membranes. Biochim. Biophys. Acta 1990, 1055: 151–156.
Loeberham H., Tokuoka R., Deisenhofer J., Huber R. Human α1-proteinase inhibitor. Crystal structure analysis of two crystal modifications: molecular model and preliminary analysis of the implications for functions. J. Mol. Biol. 1984, 177: 531–556.
Orth N.O., Kovacs W.J. The adrenal cortex. In: Wilson J.D., Foster D.W., Kronenberg D.W., Larsen P.R. (Eds.), William’s textbook of endocrinology. W.B. Saunders, Philadelphia, 1998, p. 517.
Ingenbleek Y. Thyroid function in nonthyroid illnesses. In: De Visscher M. (Ed.), The thyroid gland. Raven Press, New York, 1980, p. 499.
Benvenga S., Robbins J. Thyroid hormone efflux from monolayer cultures of human fibroblasts and hepatocytes. Effect of lipoproteins and other thyroxine transport proteins. Endocrinology 1998, 139: 4311–4318.
Benvenga S., Robbins J. Enhancement of thyroxine entry into low-density lipoprotein (LDL) receptor competent fibroblasts by LDL: an additional mode of entry of thyroxine into cells. Endocrinology 1990, 126: 933–941.
Haddad J.G., Jennings A.S., Aw T.C. Vitamin D uptake and metabolism by perfusate rat liver: influences of carrier proteins. Endocrinology 1988, 123: 498–504.
Haddad J.G., Aden D.P., Aw T.C. Plasma carriers influence the uptake of cholecalciferol by human hepatoma-derived cells. J. Bone Min. Res. 1989, 4: 243–247.
Sundaram V., Hanna H.F., Koneru L., Newman H.A.I., Falko J.M. Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation. J. Clin. Endocrinol. Metab. 1997, 82: 3241–3244.
Dieckman M.J.M., Demacker P.N., Kastelein J.J., Stalenhoef A.F., Wiersinga W.M. Increased oxidazibility of low-density lipoproteins in hypothyroidism. J. Clin. Endocrinol. Metab. 1998, 83: 1752–1755.
Benvenga S. Effect of thyroxine on low density lipoprotein oxidation. Another thyroid hormone nongenomic effect. J. Clin. Endocrinol. Metab. 1998, 83: 3337–3378.
Benvenga S., Robbins J. Lipoprotein-thyroid hormone interactions. Trends Endocrinol. Metab. 1993, 4: 194–198.
Pemberton P.A., Stein P.E., Pepys M.B., Potter J.M., Carrel R.W. Hormone binding globulins undergo serpin conformational change in inflammation. Nature 1998, 336: 257–258.
Jirasakuldech B, Schussler G.C., Yap M.G., Drew H, Josephson A, Michl J. A characteristic serpin cleavage product of thyroxine-binding globulin appears in sepsis sera. J. Clin. Endocrinol. Metab. 2000, 85: 3996–3999.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Benvenga, S., Lapa, D. & Trimarchi, F. Thyroxine binding to members and non-members of the serine protease inhibitor family. J Endocrinol Invest 25, 32–38 (2002). https://doi.org/10.1007/BF03343958
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03343958