del Balzo P, Salvatori R, Cappa M, Gertner J M
Division of Pediatric Endocrinology, New York Hospital-Cornell University, Medical College, New York.
Clin Endocrinol (Oxf). 1990 Nov;33(5):605-12. doi: 10.1111/j.1365-2265.1990.tb03898.x.
Glucocorticoids inhibit the growth hormone (GH) response to a variety of stimuli, including GH-releasing hormone (GHRH) in vivo, but they increase GHRH-stimulated GH secretion when added, in vitro, to animal and human pituitary cells. This discrepancy has led to the hypothesis that glucocorticoids act in vivo by increasing somatostatin secretion from the hypothalamus. To examine this hypothesis, we used a cholinergic drug, pyridostigmine (PD), which reduces hypothalamic somatostatin secretion. Eight normal volunteers were studied. They underwent four tests: (1) GHRH test; (2) Dex + GHRH (GHRH test after treatment the night before, with dexamethasone (Dex)); (3) PD + GHRH; (4) Dex + PD + GHRH. Dex significantly inhibited the GH response to GHRH expressed as area under the GH/time curve (AUC, microgram/1/min) (mean +/- SEM = 895.2 +/- 196.6 vs 1970.9 +/- 600.1, P less than 0.05). PD significantly increased the AUC of GH secretion in PD + GHRH compared with GHRH alone (3541.2 +/- 571.3 vs 1970.9 +/- 600.1, P less than 0.01) but by no means restored completely the normal GH response to GHRH, when given to Dex-pretreated subjects. Furthermore, the mean AUC of Dex + PD + GHRH was significantly lower than that of PD + GHRH (1621.7 +/- 500.6 vs 3541.2 +/- 571.3, P less than 0.01), demonstrating that Dex continues to exert its inhibitory effect on GH secretion in the presence of PD. These results suggest that glucocorticoid-induced GH inhibition does not act solely through an increase in hypothalamic somatostatin secretion.
糖皮质激素可抑制生长激素（GH）对多种刺激的反应，包括体内的生长激素释放激素（GHRH），但在体外将其添加到动物和人类垂体细胞时，它们会增加GHRH刺激的GH分泌。这种差异导致了一种假说，即糖皮质激素在体内通过增加下丘脑生长抑素的分泌起作用。为了检验这一假说，我们使用了一种胆碱能药物吡啶斯的明（PD），它可减少下丘脑生长抑素的分泌。对8名正常志愿者进行了研究。他们接受了四项测试：（1）GHRH测试；（2）地塞米松+GHRH（在前一晚用地塞米松（Dex）治疗后的GHRH测试）；（3）PD+GHRH；（4）地塞米松+PD+GHRH。地塞米松显著抑制了以GH/时间曲线下面积（AUC，微克/1/分钟）表示的GH对GHRH的反应（平均值±标准误=895.2±196.6对1970.9±600.1，P<0.05）。与单独的GHRH相比，PD显著增加了PD+GHRH中GH分泌的AUC（3541.2±571.3对1970.9±600.1，P<0.01），但当给予地塞米松预处理的受试者时，绝没有完全恢复GH对GHRH的正常反应。此外，地塞米松+PD+GHRH的平均AUC显著低于PD+GHRH（1621.7±500.6对3541.2±571.3，P<0.01），表明在地塞米松存在的情况下，地塞米松继续对GH分泌发挥抑制作用。这些结果表明，糖皮质激素诱导的GH抑制并非仅通过增加下丘脑生长抑素的分泌起作用。
