Scanlon M F, Weetman A P, Lewis M, Pourmand M, Rodriguez-Arnao M D, Weightman D R, Hall R
J Clin Endocrinol Metab. 1980 Dec;51(6):1251-6. doi: 10.1210/jcem-51-6-1251.
Basal TSH levels are known to rise during the evening, but the mechanism by which this rise occurs is poorly understood. The rise in TSH in response to dopamine (DA) receptor blockade with metoclopramide in the morning in normal subjects and hypothyroid patients has provided evidence for a tonic inhibitory role for DA in the control of TSH secretion. We have tested the hypothesis in normal, euthyroid volunteers (14 females, aged 20--40 yr; 12 males, aged 22--45 yr) that the nocturnal elevation of serum TSH levels might result from a reduction in DA action on the thyrotroph, in which case a reduced TSH response to metoclopramide would be expected. We found, however, that the TSH response to DA receptor blockade with metoclopramide (10 mg, iv) was significantly greater at 2300 h than at 1100 h [net incremental response over 120 min, 14.9 +/- 2.5 vs. 6.7 +/- 1.6 mU/liter (mean +/- SE); P < 0.001], indicating greater DA inhibition of TSH release at night. Thus, the nocturnal elevation of TSH is not due to decreased DA action on the thyrotroph; rather, increased DA tone is present and may limit the TSH response to other as yet unknown factors. Thyroid hormone levels also rose significantly after metoclopramide at both 1100 and 2300 h compared with control values after placebo [incremental difference (in nanomoles per liter) between 0 and 120 min values (mean +/- SE): 1100 h, T3, 0.24 +/- 0.09 vs. -0.05 +/- 0.08 (P < 0.02); T4, 19.4 +/- 6.1 vs. -1.8 +/- 2.5 (P < 0.01); 2300 h, T3 +/- 0.53 +/-0.07 vs. 0.04 +/- 0.07 (P < 0.01); T4 20.9 +/- 5.6 vs. 2.8 +/- 3.2 (P < 0.01)]. Incremental thyroid hormone and TSH responses to metoclopramide were directly related (T3 vs. TSH, r = 0.59 and P < 0.001; T4 vs. TSH, r = 0.41 and P < 0.01), suggesting that the thyroid hormone responses were mediated by TSH and illustrating the sensitivity of the thyroid gland to even small increases in endogenous TSH levels.
已知基础促甲状腺激素（TSH）水平在夜间会升高，但这种升高发生的机制尚不清楚。正常受试者和甲状腺功能减退患者早晨使用甲氧氯普胺阻断多巴胺（DA）受体后TSH升高，这为DA在控制TSH分泌中发挥的紧张性抑制作用提供了证据。我们在正常甲状腺功能的志愿者（14名女性，年龄20 - 40岁；12名男性，年龄22 - 45岁）中测试了以下假设：血清TSH水平的夜间升高可能是由于DA对促甲状腺细胞的作用减弱所致，在这种情况下，预计TSH对甲氧氯普胺的反应会降低。然而，我们发现，在23:00时，甲氧氯普胺（10 mg，静脉注射）阻断DA受体后TSH的反应显著大于11:00时[120分钟内的净增量反应，分别为14.9±2.5与6.7±1.6 mU/升（平均值±标准误）；P<0.001]，表明夜间DA对TSH释放的抑制作用更强。因此，TSH的夜间升高并非由于DA对促甲状腺细胞的作用减弱；相反，存在DA张力增加的情况，这可能会限制TSH对其他未知因素的反应。与安慰剂后的对照值相比，在11:00和23:00时，甲氧氯普胺后甲状腺激素水平也显著升高[0至120分钟值之间的增量差异（以纳摩尔/升计）（平均值±标准误）：11:00时，T3，0.24±0.09与 - 0.05±0.08（P<0.02）；T4，19.4±6.1与 - 1.8±2.5（P<0.01）；23:00时，T3，0.53±0.07与0.04±0.07（P<0.01）；T4，20.9±5.6与2.8±3.2（P<0.01）]。甲氧氯普胺引起的甲状腺激素和TSH的增量反应直接相关（T3与TSH，r = 0.59，P<0.001；T4与TSH，r = 0.41，P<0.01），表明甲状腺激素反应是由TSH介导的，并说明了甲状腺对即使是内源性TSH水平的小幅升高也很敏感。
