Llorente I, Lizcano F, Alvarez R, Diez N, Sopena M, Gil M J, Salvador J
Department of Endocrinology, University Clinic of Navarra, Pamplona, Spain.
J Clin Endocrinol Metab. 1996 Aug;81(8):2902-7. doi: 10.1210/jcem.81.8.8768849.
Controversy still exists regarding the role of cholinergic pathways in the regulation of the hypothalamic-pituitary-adrenal axis in man. We studied the effects of the administration of placebo, pyridostigmine (PD); 120 mg, orally), and the combination of PD and pirenzepine (PZP; 100 mg, orally) on ACTH, cortisol, and GH secretion at 0730 and 2230 h in seven normal males. PD induced a clear decrease in ACTH levels at both times of the day compared to treatment with placebo, producing higher suppression in the nocturnal period (34.4 +/- 5.8% vs. 21.8 +/- 10.7%). The combination PD and PZP prevented the inhibitory action of PD on ACTH secretion in the morning, but not in the evening, when ACTH values showed a decrease similar to that seen after giving PD alone (38.1 +/- 5.6% vs. 34.4 +/- 5.8%, respectively). Cortisol values declined only when the association PD plus PZP was given in the evening. GH levels had a significant increase after PD administration in the morning (4.1 +/- 1.2 ng/mL) and in the evening (10.2 +/- 1.6 ng/mL), confirming that cholinergic stimulation was taking place, whereas the addition of PZP to PD induced a significant attenuation of these responses. It is concluded that cholinergic pathways have a inhibitory role in ACTH secretion in man. M1 muscarinic receptors seem to be involved in the diurnal inhibition of PD, whereas our observations are consistent with the mediation of another type of cholinergic receptors as an explanation for the nocturnal effect of PD on ACTH secretion. PD did not alter the circadian variation in the hypothalamic-pituitary-adrenal axis, whereas the association of PD and PZP increased the differences between diurnal and nocturnal ACTH values, suggesting a modulatory effect of the cholinergic system on the circadian rhythm of ACTH secretion.
关于胆碱能通路在人类下丘脑 - 垂体 - 肾上腺轴调节中的作用，目前仍存在争议。我们研究了安慰剂、吡啶斯的明（PD；口服120毫克）以及PD与哌仑西平（PZP；口服100毫克）联合用药对7名正常男性在0730和2230时促肾上腺皮质激素（ACTH）、皮质醇和生长激素（GH）分泌的影响。与安慰剂治疗相比，PD在一天中的两个时间点均使ACTH水平明显降低，在夜间产生更高的抑制作用（34.4±5.8%对21.8±10.7%）。PD与PZP联合用药可防止PD在早晨对ACTH分泌的抑制作用，但在晚上则不能，此时ACTH值的降低与单独给予PD后相似（分别为38.1±5.6%对34.4±5.8%）。仅在晚上给予PD加PZP联合用药时，皮质醇值才会下降。早晨（4.1±1.2纳克/毫升）和晚上（10.2±1.6纳克/毫升）给予PD后，GH水平显著升高，证实发生了胆碱能刺激，而在PD中加入PZP会导致这些反应显著减弱。结论是胆碱能通路在人类ACTH分泌中具有抑制作用。M1毒蕈碱受体似乎参与了PD的昼夜抑制作用，而我们的观察结果与另一种胆碱能受体的介导作用一致，可解释PD对ACTH分泌的夜间效应。PD并未改变下丘脑 - 垂体 - 肾上腺轴的昼夜变化，而PD与PZP联合用药增加了昼夜ACTH值之间的差异，表明胆碱能系统对ACTH分泌的昼夜节律具有调节作用。
