Genetic control of thyroxine transport

Abstract

Almost all of the thyroid hormone in the plasma of primates is associated with transport proteins, with an extremely small proportion (~0.03%) in the unbound state¹. Thyroxine-binding globulin (TBG) is quantitatively the most important, carrying approximately 75% of circulating thyroxine (T₄) and triiodothyronine (T₃). Thyroxine-binding prealbumin (PA) is another relatively specific transport protein, but is involved mainly in T₄ transport. Serum albumin also binds T₄ and T₃, as it does many other small molecules in blood. Recently, Hoch and Lewallen² have confirmed earlier suggestions that the plasma lipoproteins transport a minor proportion of the circulating hormones, and in the foetus³ the so-called foetal post-albumin also shows an affinity for T₄. Up to the present time, however, no specific role for any of these proteins has been demonstrated, and the major ones appear to function solely as a buffering system for the extrathyroidal hormones. Hillier⁴ has shown that the rates of dissociation of the hormones from protein are extremely rapid, and indeed rapid enough to permit the expected flux of free hormone in the microcirculation. Although it is possible that in particular tissues some of the transport proteins may function more specifically, the subject I will discuss cannot be related in any obvious way to the control of thyroid hormone action. Nevertheless, the genetic alterations affecting the transport proteins are significant in clinical testing of thyroid function, and also represent an interesting system for the study of genetic influence on plasma protein levels.