Reduced triiodothyronine content in liver but not pituitary of the uremic rat model: demonstration of changes compatible with thyroid hormone deficiency in liver only.
Intracellular thyroid hormone concentration and action were examined in the liver and the pituitary of a nephrectomized rat model (Nx); the results were compared with those obtained from control (C), thyroidectomized (Tx), and nephrectomized-thyroidectomized (NxTx) littermates. Based on the severity of the uremia, Nx rats were subdivided into Nx1 and Nx2 groups; the former included rats with serum urea nitrogen of less than 100 mg/dl and the latter rats with serum urea nitrogen greater than 100 mg/dl. A group of rats pair-fed to the Nx rats was also included (PF). In the liver, nuclear T3 content (picograms per g liver) and T3-receptor binding capacity (Cmax, picograms T3 per mg DNA) were measured. The respective results from all groups of rats were as follows (asterisks denote values differing from C with a P value less than 0.05): C, 308 +/- (SE) 45 and 121 +/- 11; Nx1, 245 +/- 43 and 85 +/- 15; Nx2, 163 +/- 19 and 74 +/- 7; Tx, 43 +/- 11 and 91 +/- 10; NxTx, 33 +/- 10 and 54 +/- 6; and PF, 237 +/- 20 and 121 +/- 9. T3 receptor binding affinity (Ka), ranging from 3.62-5.28 X 10(9) M-1, was not significantly different among the six groups of rats. In the pituitary, T3 content (picograms per mg pituitary) was reduced only in the Tx rats, being 3.13 +/- 0.89 as compared to 7.04 +/- 1.48 in the C rats (P less than 0.05). In the Nx1, Nx2, and PF rats, pituitary T3 contents were 9.81 +/- 3.22, 13.01 +/- 3.60, and 7.83 +/- 1.08, respectively, and were not different from the C rats. Serum TSH was reciprocally elevated only in the Tx rats. The reduction in hepatic nuclear T3 content and T3-Cmax in the Nx2 rats is consistent with the presence of selective tissue deficiency of thyroid hormone. This is in agreement with the observation of reduced activity of two liver enzymes known to be under thyroid hormone regulation. The pituitary, however, had normal T3 content, suggesting a dissociation in thyroid hormone-dependent metabolic status between a peripheral tissue (liver) and the pituitary. This explains the failure to observe an increase in the serum TSH level, a manifestation of reduced intracellular rather than serum T3 concentration. Decreased food intake appeared not to be the cause of thyroid hormone abnormalities observed in uremia, as PF rats failed to manifest the changes found in Nx rats.
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D009929:Organ Size; D009928:Organ Specificity; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011988:Receptors, Thyroid Hormone; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism*
D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine