Szabo M, Ruestow P C, Kramer D E
Endocrinology. 1985 Jul;117(1):330-7. doi: 10.1210/endo-117-1-330.
To evaluate the role of thyroid hormones in regulation of the GH-stimulatory effects of TRH and human pancreatic GH-releasing factor (hpGRF-40), we studied the plasma GH responses to these secretagogues under conditions of thyroid hormone deprivation and replacement in the urethane-anesthetized rat. In euthyroid control rats, TRH (1 microgram/kg) elicited a small transient rise in plasma GH, which peaked at 2-5 min and returned to basal by 20 min. In chronically hypothyroid rats (10 weeks after thyroidectomy), intrapituitary GH was markedly depleted to less than 0.1% of normal, and TRH was completely ineffective in eliciting a plasma GH response to TRH. In chronically hypothyroid rats given T4 (20 micrograms/kg daily) for 4 days, intrapituitary GH was partially repleted, and the GH response to TRH was markedly enhanced compared to that in euthyroid rats. The extent to which the GH response to TRH was enhanced by chronic hypothyroidism, followed by short term T4 treatment, depended on the duration of T4 administration. The plasma GH response was greatest after 1-3 days of T4 treatment; treatment for 7 days, on the other hand, suppressed the GH response to below that of euthyroid rats. The minimal duration of hypothyroidism which, in combination with short term (2 days) T4 treatment, enhanced the plasma GH response to TRH, was 6 weeks, with 8 weeks or longer being optimal. The effect of TRH on plasma GH was dose dependent in thyroidectomized rats given T4 for 2 days; the lowest maximally stimulatory dose was 10 times less than that in the euthyroid rat (1 vs. 10 micrograms/kg). The GH-stimulatory effect of TRH in thyroidectomized rats given T4 for 2 days was abolished by the simultaneous administration of SRIF (40 micrograms/kg). That the failure of TRH to stimulate GH release in the chronically hypothyroid rat may have been the consequence of a depletion of intrapituitary GH available for release was suggested by the finding that in parallel studies, hpGRF-40, a more potent stimulator of GH release in the euthyroid rat, was also without effect. In contrast to the GH response to TRH, the GH response to hpGRF-40 was only partially restored by T4 treatment of chronically hypothyroid rats for 2 days. We conclude that chronic thyroid hormone deficiency selectively sensitizes the somatotroph to TRH. Short term thyroid hormone replacement is needed to replete intrapituitary GH and allow the expression of this enhanced GH secretory response to TRH. More prolonged treatment with T4, on the other hand, appears to desensitize the somatotroph to TRH.
为了评估甲状腺激素在调节促甲状腺激素释放激素（TRH）和人胰腺生长激素释放因子（hpGRF - 40）对生长激素（GH）的刺激作用中的作用，我们在氨基甲酸乙酯麻醉的大鼠中，研究了甲状腺激素缺乏和替代情况下，这些促分泌素引起的血浆GH反应。在甲状腺功能正常的对照大鼠中，TRH（1微克/千克）引起血浆GH出现短暂小幅升高，在2 - 5分钟达到峰值，20分钟时恢复到基础水平。在慢性甲状腺功能减退大鼠（甲状腺切除术后10周）中，垂体GH明显减少至正常水平的不到0.1%，TRH完全无法引起血浆GH反应。在给予四碘甲状腺原氨酸（T4，20微克/千克/天）4天的慢性甲状腺功能减退大鼠中，垂体GH部分恢复，与甲状腺功能正常的大鼠相比，对TRH的GH反应明显增强。慢性甲状腺功能减退后短期给予T4治疗，对TRH的GH反应增强的程度取决于T4给药的持续时间。T4治疗1 - 3天后血浆GH反应最大；另一方面，治疗7天则将GH反应抑制至低于甲状腺功能正常大鼠的水平。与短期（2天）T4治疗相结合，能增强血浆GH对TRH反应的甲状腺功能减退的最短持续时间为6周，8周或更长时间最为理想。在给予T4 2天的甲状腺切除大鼠中，TRH对血浆GH的作用呈剂量依赖性；最低最大刺激剂量比甲状腺功能正常大鼠低10倍（1微克/千克对10微克/千克）。在给予T4 2天的甲状腺切除大鼠中，同时给予生长抑素（SRIF，40微克/千克）可消除TRH对GH的刺激作用。在平行研究中发现，hpGRF - 40（在甲状腺功能正常大鼠中是一种更强的GH释放刺激剂）也无作用，这表明在慢性甲状腺功能减退大鼠中TRH未能刺激GH释放可能是由于可供释放的垂体GH耗竭所致。与对TRH的GH反应相反，慢性甲状腺功能减退大鼠经T4治疗2天，对hpGRF - 40的GH反应仅部分恢复。我们得出结论，慢性甲状腺激素缺乏选择性地使生长激素细胞对TRH敏感。需要短期甲状腺激素替代来补充垂体GH，并使这种增强的GH对TRH的分泌反应得以表达。另一方面，更长时间的T4治疗似乎会使生长激素细胞对TRH脱敏。
