Connors J M, DeVito W J, Hedge G A
Endocrinology. 1984 May;114(5):1930-7. doi: 10.1210/endo-114-5-1930.
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.
我们研究了严重甲状腺功能减退(甲状腺切除术)的持续时间和衰老对雌性大鼠垂体促甲状腺激素(TSH)对外源性促甲状腺激素释放激素(TRH)的反应以及TSH代谢清除率(MCR)的影响。在实验前4、14或68天,将大鼠进行甲状腺切除(THYREX)或假手术(SHAM)。所有大鼠均植入慢性心房导管,通过该导管给予TRH(0、250或1000 ng/100 g体重)或[125I]TSH,并采集连续的血样。根据注射的[125I]碘-TSH的血浆消失曲线,测定每组大鼠的TSH MCR,发现4天甲状腺切除组的MCR降低[0.23±0.01(±标准误)对0.27±0.01 ml/min×100 g;P<0.05],但与年龄匹配的假手术对照组相比,14天甲状腺切除组或68天甲状腺切除组大鼠的MCR未降低。此外,与4天或14天假手术组大鼠相比,68天假手术组大鼠的TSH MCR降低(0.15±0.01对0.27±0.01 ml/min×100 g;P<0.05)。计算了每组大鼠对每剂TRH反应分泌的TSH量(MCR×血浆TSH变化曲线下面积×体重),发现4天甲状腺切除组大鼠分泌的TSH量降低(4.5±1.5对30.0±4.5微克;P<0.05),但与年龄匹配的假手术对照组相比,14天或68天甲状腺切除组大鼠分泌的TSH量无差异。与4天或14天假手术组大鼠相比,68天假手术组大鼠对TRH反应分泌的TSH量也减少(16.0±1.0对30.0±4.5微克;P<0.05)。这些结果表明:1)衰老会降低大鼠TSH的MCR,但严重甲状腺功能减退不会;2)衰老会降低大鼠垂体TSH对外源性TRH的反应;3)在严重甲状腺功能减退期间,与年龄匹配的甲状腺功能正常的大鼠相比,大鼠垂体对中等剂量或最大剂量TRH的TSH反应降低(4天甲状腺切除组)或无差异(14天和68天甲状腺切除组)。