Thyroid function in Gunn rats with genetically altered thyroid hormone catabolism

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Abstract
Due to a congenital deficiency in UDP glucuronosyl transferase (UDP-GTase), Gunn [G] rats display an impaired biliary elimination of both bilirubin and thyroid hormones, resulting in hyperbilirubinemia and hyperthyroxinemia. They also present a pigmented thyroid gland. To assess the effect of the hyperthyroxinemia on the regulation of the thyroid function, the [125I]thyroid uptake and distribution into soluble proteins, the [127I]thyroid soluble content, the levels of circulating T4 [thyroxine], total and free, T3 [triiodothyronine], reverse T3 (rT3) and TSH, and the TSH response to TRH were determined in and G and Wistar (W) rats aged 3-56 wk. G rats possess a goiter with increased soluble [127I]-iodine content. The [125I]thyroid uptake and incorporation into soluble proteins were similar in both strains, but the diiodotyrosine fraction was higher, whereas the monoiodotyrosine, T4 and T3 fractions were lower compared to control rats. Total thyroxinemia was greatly increased in G rats as expected (G:5.1-9.1 vs. W:3.1-4.6 .mu.g/dl) whereas free thyroxinemia was increased only by 25-50%. The differences in total-T4 and bilirubin serum levels between G and W rats 6-56 wk old were in direct correlation. In addition, G rats presented normal serum T3 levels, but increased rT3 (G:0.10-0.45 vs. W: < 0.03-0.27 ng/ml) and TSH (G:0.33-0.75 vs. W:0.11-0.43 ng/ml) serum levels. The TSH response to TRH was however normal, but the return to basal values was delayed in comparison to W rats. Evolution of thyroid parameters with age was similar in both strains, i.e. opposite variations in T3 and rT3 serum values during the post-natal period and decreasing serum T4 concentrations, pituitary TSH content and TSH response to TRH during the adult life. The association of hyperthyroxinemia with decreased T3/rT3 serum ratio suggests that G rats may have, in addition to the impaired biliary excretion of iodothyronines, a modified T4 deiodination pattern with probably increased rT3 formation. A diminished T4 availability and/or a decreased T4 to T3 conversion in the thyrotrope cell might explain the normal TSH response to TRH. These data reflect a partial peripheral resistance to the hyperthyroxinemia, which may represent an adaptation mechanism.