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

The effects of the duration of severe hypothyroidism (thyroidectomy) and aging on the pituitary TSH response to exogenous TRH and the TSH MCR [metabolic clearance rate] in female rats were studied. 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 body wt) 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 .cntdot. 100 g; P < 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 decreased in 68-day-SHAM compared to 4- or 14-day-SHAM rats (0.15 .+-. 0.01 vs. 0.27 .+-. 0.01 ml/min .cntdot. 100 g; P < 0.05). The amount of TSH secreted (MCR .cntdot. area under .DELTA. plasma TSH curve .cntdot. body wt) in response to each dose of TRH was calculated and was decreased in 4-day-THYREX rats (4.5 .+-. 1.5 vs. 30.0 .+-. 4.5 .mu.g; P < 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 .mu.g; P < 0.05). The MCR of TSH is decreased by aging, but not by severe hypothyroidism in the rat; the pituitary TSH response of the rat to exogenous TRH is decreased by aging, and 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.