J. Thomas Dowling

THYROXINE-BINDING BY SERA OF PREGNANT WOMEN, NEW-BORN INFANTS, AND WOMEN WITH SPONTANEOUS ABORTION

Among the many physiological alterations which may occur during pregnancy are thyromegaly (1), augmented thyroidal avidity for iodine (2, 3), and increase in the concentration of circulating thyroid hormone (4, 5). This triad of anatomical and functional alterations is ordinarily considered to be diagnostic of thyrotoxicosis. Paradoxically, however, these findings are neither accompanied by symptomatic stigmata of hyperthyroidism, nor are they associated, during the first half of pregnancy, with increase in the basal metabolic rate. Although the basal metabolic rate increases during the latter half of pregnancy, this change has been ascribed by some to fetal needs, and not to alterations in maternal energy requirements (6). The origins and consequences of this unique functional dissociation are unknown. Recently there has been considerable interest in the physiological role and physicochemical properties of the specific thyroxine-binding protein or proteins of plasma (TBP). Although the physiological role of TBP has not been elucidated, demonstration of this alpha globulin moiety in 1952 provided another parameter of thyroidal economy which is susceptible to measurement (7-11). Even earlier it had been suggested that the increased SPI of pregnancy might result from an alteration in the manner in which thyroxine in plasma is protein-bound (12, 13). Therefore, it appeared possible that study of the thyroxine-

THE INTERACTION OF THYROXINE WITH PLASMA PROTEINS: LOCALIZATION OF THYROXINE-BINDING PROTEIN IN COHN FRACTIONS OF PLASMA

Recently zone electrophoretic techniques have been employed to characterize the site of thyroxine-binding in plasma (1-7). In most reports, an association has been described between thyroxine and a protein moiety intermediate in electrophoretic mobility at pH 8.6 between the al and the a, globulins. A concentrated source of this thyroxine-binding protein (TBP) has not been available for further purification or for experimental evaluation of its physiological role. To meet these objectives, zone electrophoretic techniques have been employed to localize TBP in subfractions of plasma prepared by Method 6 of Cohn and his co-workers (8, 9).

Estimation of thyroxine distribution in man

A group of 13 normal subjects were evaluated for their extrathyroidal thyroxine distribution. The method employed the measurement of the acute plasma disappearance of a thyroxine-(131)I tracer and its concomitant uptake into the liver and forearm. The analysis of these parameters allowed the theoretical construction of a four compartmental mathematical model system comprised of the plasma, extracellular fluid, hepatic, and extrahepatic thyroxine pools. The results of this analysis revealed that the exchange of thyroxine from the plasma into the hepatic and extrahepatic cellular fluid spaces appeared, in general, to be rapid, while the uptake into the extrahepatic tissues was relatively slow. The calculated distribution of thyroxine at equilibrium was estimated to be 14% in liver, 34% in extrahepatic tissues, and 26% each in the plasma and extracellular fluid pools in this group of normal subjects.