Investigations into the etiology of elevated serum T₃ levels in protein-malnourished rats

Thyroid function studies and the peripheral metabolism of thyroid hormone were examined in rats fed a low protein diet (9% casein) for 4-8 wk. Compared to animals fed a normal protein diet ad libitum, both the low protein rats and a pair-fed control group weighed less at the end of the study. However, serum total T₃ levels were significantly higher only in the protein deficient rats. The elevated serum T₃ was not explainable by enhanced peripheral T₄ to T₃ conversion, as there was no evidence of any change in hepatic or renal 5′-deiodinase activity when homogenates were examined for conversion of T₄ to T₃, reverse T₃ to 3,3′-diiodothyronine, or 3′,5′-diiodothyronine to 3′-monoiodothyronine. Neither was there an effect on hepatic T₃ receptor maximal binding capacity (204 ± 24 versus 168 ± 15 fmol/mg DNA control) or binding affinity (2.07 ± 0.38 versus 2.49 ± 0.24 × 10^-10 M control). In two separate experiments the dialyzable fraction of T₃ was significantly lower in the low protein group while free T₃ concentrations were unchanged or reduced. In contrast, serum total and free T₄ were either normal or reduced and dialyzable T₄ was unaffected by protein deficiency. We conclude that while serum total T₃ is elevated in rats chronically fed a low protein diet, this elevation is not due to enhanced T₄ to T₃ conversion. Rather, the increased T₃ levels can be accounted for by a striking alteration in protein binding to T₃. Moreover, the failure to demonstrate similar changes in serum total and dialyzable T₄ suggests that in the rat, protein deficiency has different effects on binding to the two major thyroid hormones. Dietary induced changes in serum thyroid hormone binding must be kept in mind in nutrition studies in the rat.