Ambrosio M R, Campo M, Zatelli M C, Cella S G, Trasforini G, Margutti A, Rigamonti A E, Müller E E, degli Uberti E C
Department of Biomedical Sciences and Advanced Therapies - Section of Endocrinology, University of Ferrara, Italy.
Neuroendocrinology. 1998 Aug;68(2):123-8. doi: 10.1159/000054358.
In this study we explored, in man, the effect of acute attenuation of growth hormone (GH) release induced by somatostatin (SRIH) on ACTH and cortisol plasma levels. Sixteen young (8 women, aged 23-32 years, and 8 men, aged 18-27 years) and 14 elderly (8 women, aged 65-82 years, and 6 men, aged 65-70 years) healthy subjects volunteered to participate in this investigation. Each subject was tested on two separate occasions by: (1) a 90-min i.v. infusion of SRIH given in 50 ml 0.9% saline delivered at a rate of 9 microg/kg/h, and (2) a 90-min i.v. infusion of isovolumetric amounts of 0.9% saline. Plasma GH, ACTH, cortisol and glucose concentrations were determined prior and up to 180 min after SRIH or saline infusion. SRIH induced a significant (p < 0.05) decrease in plasma GH levels from basal values of 0.6 +/- 0.15 and 0.5 +/- 0.15 microg/l to nadir values 0.25 +/- 0.1 and 0.2 +/- 0.1 microg/l in young and elderly subjects, respectively. The administration of SRIH was associated with a clear-cut increase in plasma ACTH levels both in young (peak, 10.6 +/- 1.6 pmol/l; AUC, 558.6 +/- 147.5 pmol/l/h) and in elderly (peak, 21.3 +/- 5.6 pmol/l; AUC, 841.9 +/- 153.8 pmol/l/h) subjects with a significant (p < 0.01) difference as compared to saline infusion. Consistent with these results, SRIH infusion resulted in an unequivocal rise in plasma cortisol levels both in young (peak, 394.8 +/- 36.4 nmol/l; AUC, 18,591.62 +/- 1,372.45 nmol/l/h) and in elderly (peak, 585.6 +/- 51.5 nmol/l; AUC, 24,871.05 +/- 1,837.03 nmol/l/h) subjects. The ACTH and cortisol responses to SRIH were significantly (p < 0.05 and p < 0.01) higher in elderly than in young subjects. No sex-related differences occurred in the SRIH-induced activation of hypothalamic-pituitary-adrenocortical (HPA) axis. We conclude that (1) infusion of SRIH, at a dose that inhibited basal GH secretion, was associated with an activation of HPA axis, and (2) this response was higher in elderly individuals compared with younger adults. The reason for this novel and unexpected SRIH effect is presently unclear; however, the latter may be mediated, at least in part, by some central nervous system ACTH-releasing mechanisms activated by SRIH-induced decrease in GH secretion.
在本研究中，我们探讨了在人体中，生长抑素（SRIH）诱导的生长激素（GH）释放急性减弱对促肾上腺皮质激素（ACTH）和血浆皮质醇水平的影响。16名年轻健康受试者（8名女性，年龄23 - 32岁，8名男性，年龄18 - 27岁）和14名老年健康受试者（8名女性，年龄65 - 82岁，6名男性，年龄65 - 70岁）自愿参与本研究。每位受试者在两个不同的时间段接受测试：（1）以9微克/千克/小时的速率静脉输注90分钟的SRIH，用50毫升0.9%生理盐水配制；（2）静脉输注90分钟等体积的0.9%生理盐水。在输注SRIH或生理盐水之前以及之后长达180分钟内，测定血浆GH、ACTH、皮质醇和葡萄糖浓度。SRIH使年轻受试者血浆GH水平从基础值0.6±0.15微克/升和0.5±0.15微克/升分别显著（p < 0.05）降至最低点0.25±0.1微克/升和0.2±0.1微克/升，老年受试者也有类似情况。SRIH的给药与年轻受试者（峰值，10.6±1.6皮摩尔/升；曲线下面积，558.6±147.5皮摩尔/升/小时）和老年受试者（峰值，21.3±5.6皮摩尔/升；曲线下面积，841.9±153.8皮摩尔/升/小时）血浆ACTH水平的明显升高相关，与输注生理盐水相比有显著（p < 0.01）差异。与这些结果一致，SRIH输注导致年轻受试者（峰值，394.8±36.4纳摩尔/升；曲线下面积，18,591.62±1,372.45纳摩尔/升/小时）和老年受试者（峰值,585.6±51.5纳摩尔/升；曲线下面积，24,871.05±1,837.03纳摩尔/升/小时）血浆皮质醇水平明确升高。老年受试者对SRIH的ACTH和皮质醇反应显著（p < 0.05和p < 0.01）高于年轻受试者。在SRIH诱导的下丘脑 - 垂体 - 肾上腺皮质（HPA）轴激活方面未出现性别相关差异。我们得出结论：（1）输注抑制基础GH分泌剂量的SRIH与HPA轴激活相关；（2）与年轻成年人相比，老年人的这种反应更高。这种新型且意外的SRIH效应的原因目前尚不清楚；然而，后者可能至少部分由SRIH诱导的GH分泌减少激活的一些中枢神经系统促肾上腺皮质激素释放机制介导。
