Variant thyroxine-binding globulin in serum of Australian Aborigines: its physical, chemical and biological properties

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Abstract
Low serum total thyroxine (TT4) and triiodothyronine (TT3) is found in approximately 40% of Australian Aborigines. Studies were carried out to characterize the properties of thyroxine-binding globulin (TBG) in these Australian Aborigines to explain the observed reduction of thyroid hormone concentration in their serum. TBG from Aborigines with low serum TT4 concentrations was compared to TBG fram Aborigines with normal TT4 concentration and Caucasians and American Blacks with normal or reduced serum TBG levels due to familial partial TBG deficiency. TBG from Aborigines with low serum TT4 concentrations had a reduced affinity for thyroid hormone (Ka). The Ka for T4 was 54% and for T3 30% of the Ka values for TBG from Aborigines with normal TT4 concentration or non-Aborigines. Maximal binding values were in agreement with TBG measurements by RIA for Aborigines with low or normal serum TT4 and for non-Aborigines. An increase in the rate of heat denaturation of TBG at temperatures from 54 to 60 C was also observed in sera from Aborigines with low TT4. The heat lability was lowered by 2 C. The low concentration of TT4 in serum of these Aborigines could not explain this higher heat lability of TBG since only addition of greater than 80-fold the physiologic T4 concentration obliterated the difference of heat inactivation by denaturation. Nevertheless, decreased T4 occupancy of this TBG with lower affinity for thyroid hormone may explain reduced stability at high temperatures. There were no differences in the microheterogeneity by isoelectric focusing between TBGs from Aborigines with low serum TT4 concentration and those with normal TT4 or non-Aborigines. From data on maximal binding capacity and TBG measurement by radioimmu-noassy it could be determined that TBG in these Aborigines as in non-Aborigines has a single thyroid hormone binding site. These results indicate that euthyroid Aborigines with low serum TT4 and TT3 concentrations have a variant TBG with reduced affinity for these hormones. The difference between this variant TBG as compared to the more common type of TBG in non-Aborigines appears to reside in the polypeptide chain rather than in the carbohydrate moiety. It fully accounts for the reduced serum total thyroid hormone concentration in the presence of clinical euthyroidism with normal serum free T4 and thyrotropin levels.