Peripheral metabolism of homologous thyrotropin in euthyroid and hypothyroid rats: acute effects of thyrotropin-releasing hormone, triiodothyronine, and thyroxine.

The peripheral metabolism and metabolic clearance rate (MCR) of homologous TSH was studied in euthyroid and hypothyroid rats. Incubation of freshly labeled [125I]iodo-TSH with rat serum revealed a labeled nonimmunoreactive protein in the void volume of a Sephadex G-100 column which could not be detected by conventional chromatographic purification. Removal of this contaminant from the tracer reduced the nonspecific binding in the absence of serum and increased the binding of tracer in the absence of added exogenous TSH. Injection of [125I]iodo-TSH into rats was followed within 15 min by the appearance of at least three labeled protein components. Gel filtration showed that these peaks were trichloroacetic acid (TCA)-precipitable proteins of larger molecular weight than TSH, but not all were precipitable by antibody to rat TSH. The disappearance rate of TCA-precipitable 125I (t1/2 = 28 min) was significantly longer than the disappearance rate of immunoprecipitable 125I (t1/2 = 22 min). The disappearance rate of immunoprecipitable [125I]iodo-TSH was identical to that of injected purified rat TSH and of the TRH-induced TSH increment in euthyroid rats. The disappearance rate os suppressible TSH (after 100 microgram T3) in hypothyroid animals was only slightly longer than the rate of disappearance of immunoprecipitable [125I]iodo-TSH (40 vs. 36 min) in the same rats. The calculated MCR of TSH was slightly lower (P less than 0.05) in hypothyroid rats (18.3 +/- 3.0 ml/h/100 g BW, mean +/- SD) than it was in euthyroid rats (22.6 +/- 2.1). The pituitary TSH concentration in hypothyroid rats was 29 mU/mg wet wt, similar to that of euthyroid animals. These results indicate that the turnover rate of pituitary TSH in hypothyroid rats with serum TSH concentrations of 1400-3000 microunit/ml is 7-14 times/day. Therefore, the significant increase we observed in pituitary TSH concentration 1 h after T4 (1.5 microgram/100 g BW) or T3 (0.15 microgram/100 g BW) administration indicates that the 35% decrease in plasma TSH at this interval is due to inhibition of TSH release, not to inhibition of TSH synthesis.