The effects of the duration of severe hypothyroidism and aging on the metabolic clearance rate of thyrotropin (TSH) and the pituitary TSH response to TSH-releasing hormone

Abstract

We have studied the effects of the duration of severe hypothyroidism (thyroidectomy) and aging on the pituitary TSH response to exogenous TRH and the TSH MCR in female rats. Rats were thyroidectomized (THYREX) or sham operated (SHAM) 4, 14, or 68 days before experimentation. All rats were prepared with chronic intraatrial catheters through which TRH (0, 250, or 1000 ng/100 g BW) or [125I]TSH was administered, and sequential blood samples were obtained. The MCR of TSH was determined in each group from the plasma disappearance curves of injected [125I]iodo-TSH and were found to be decreased in 4-day-THYREX [0.23 +/- 0.01 (+/- SE) vs. 0.27 +/- 0.01 ml/min X 100 g; P less than 0.05], but not in 14-day-THYREX or 68-day-THYREX rats compared with age-matched SHAM controls. In addition, the TSH MCR was found to be decreased in 68-day-SHAM compared to 4- or 14-day-SHAM rats (0.15 +/- 0.01 vs. 0.27 +/- 0.01 ml/min X 100 g; P less than 0.05). The amount of TSH secreted (MCR X area under delta plasma TSH curve X BW) in response to each dose of TRH was calculated and was found to be decreased in 4-day-THYREX rats (4.5 +/- 1.5 vs. 30.0 +/- 4.5 micrograms; P less than 0.05), but not different in 14-day- or 68-day-THYREX rats compared with age-matched SHAM controls. The amount of TSH secreted in response to TRH was also reduced in 68-day-SHAM compared with 4- or 14-day-SHAM rats (16.0 +/- 1.0 vs. 30.0 +/- 4.5 micrograms; P less than 0.05). These results indicate that 1) the MCR of TSH is decreased by aging, but not by severe hypothyroidism in the rat; 2) the pituitary TSH response of the rat to exogenous TRH is decreased by aging, and 3) during severe hypothyroidism, the pituitary TSH response of the rat to a midrange or maximal dose of TRH is decreased (4-day-THYREX) or not different (14- and 68-day-THYREX) compared with that of age-matched euthyroid rats.