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 x 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.