The hepatocellular thyroid status of uremic rats estimated from the abundances of thyroid hormone-dependent nucleoplasmic proteins

Although the serum thyroxine (T 4) and triiodothyronine (T 3) concentrations of uremic rats are commensurate with moderate hypothyroidism, their thyroid status at the tissue level remains controversial. To help establish the hepatocellular thyroid status of uremic rats, a novel tissue marker (nuclear protein abundances) was evaluated in uremic rats (U), hypothyroid rats (H), and hypothyroid uremic rats (HU). Uremia was established by five-sixths nephrectomy. Moderate hypothyroidism was established by partial thyroidectomy or by provision of drinking water supplemented with propylthiouracil and T 4. Normal rats (N) and pair-fed, sham-operated rats (1 to 3 weeks after surgery) served as controls. Animals were killed 1 to 5 weeks postoperatively. The following values were obtained 5 weeks after surgery, at which time the total and free serum T 4 and T 3 levels of the hypothyroid rats (H) were equivalent to those of the uremic rats (U). Total T 4 (μg/dL ± 1 SD): N, 5.4 ± 1.7; H, 2.2 ± 0.5; U, 1.9 ± 1.5; HU, 0.5 ± 0.0. Free T 4 (ng/dL ± 1 SD): N, 535 ± 165; H, 126 ± 37; U, 135 ± 89; HU, 26 ± 1. Total T 3 (ng/dL ± 1 SD): N, 63 ± 20; H, 39 ± 14; U, 38 ± 18; HU, 13 ± 4. Free T 3 (ng/dL ± 1 SD): N, 7.83 ± 3.00; H, 3.87 ± 1.05; U, 3.47 ± 1.73; HU, 0.94 ± 0.47. Hepatocellular thyroid status was estimated from the relative abundances of two nucleoplasmic proteins on polyacrylamide gel electrophoregrams. As previously reported, an increase in the abundance of one protein (“t”, molecular weight [MW] ∼ 70,000) in conjuction with a reduction of a second protein (“n”, MW ∼ 125,000) is highly specific for hypothyroidism. The t n ratios determined by gel densitometry 5 weeks postoperatively were: N, 0.64 ± 0.12; H, 1.82 ± 0.48; U, 0.81 ± 0.21; HU, 1.91 ± 0.54. The t n ratios of the hypothyroid animals (H and HU) were significantly greater than groups N and U by Scheffe's test ( P ≤ .05). The t n ratio of group U was essentially normal. The finding of an elevated t n ratio in the hypothyroid uremic animals (HU) indicates that the uremic state itself would not mask the expression of an elevated t n ratio in the uremic rats (U) were the latter group hypothyroid. On the basis of this tissue marker, hepatocytes in uremia appear to be functionally “euthyroid.” Thus, the depressed serum total and free thyroid hormone concentrations in uremic rats do not uniformly reflect thyroid status at the tissue level.