Inder W J, Livesey J H, Ellis M J, Evans M J, Donald R A
Department of Endocrinology, Christchurch Hospital, University of Otago, New Zealand.
Clin Endocrinol (Oxf). 1996 Jan;44(1):7-13. doi: 10.1046/j.1365-2265.1996.630452.x.
It has been demonstrated that beta-endorphin reduces CRH production and hypoglycaemia-induced ACTH secretion in the rat. We aimed to determine whether supraphysiological levels of beta-endorphin inhibit the ACTH and CRH response to insulin-induced hypoglycaemia in human subjects.
Plasma glucose, prolactin, cortisol, ACTH, CRH and AVP were measured at intervals over a 3-hour period. Intravenous beta-endorphin 5 mg/50 ml or an equal volume of normal saline was infused between 30 and 90 minutes, with soluble insulin 0.15 units/kg administered i.v. at 60 minutes in a cross-over design.
Six healthy male volunteers aged 20-35 years.
Prolactin was measured by a fluoroimmunometric assay, ACTH, CRH and AVP by radioimmunoassay, and cortisol was measured by enzyme-linked immunosorbent assay. Haemodynamic measurements were recorded prior to each blood sample. Results are expressed as mean +/- standard error of the mean.
beta-Endorphin resulted in a significant decrease in baseline cortisol (P < 0.05) but not ACTH. Plasma glucose (P < 0.001) and CRH (P < 0.05) and PRL (P < 0.05) increased significantly during beta-endorphin compared to normal saline. After insulin administration, glucose reached a similar nadir during beta-endorphin and normal saline (2.1 +/- 0.1 and 1.9 +/- 0.15 mmol/l, respectively) but the fall in plasma glucose was delayed during beta-endorphin (P < 0.01 by ANOVA). This resulted in a significantly altered time-course for the ACTH and cortisol responses (P < 0.05 for each), but no difference overall in the magnitude of the response. In contrast, neither the timing nor the magnitude of the CRH and AVP responses were affected. Prolactin also reached a similar peak value after the administration of insulin, while the haemodynamic responses to hypoglycaemia were not significantly altered during beta-endorphin.
While beta-endorphin has been shown to be inhibitory to basal ACTH and cortisol secretion in humans, we note a significant increase in plasma CRH in response to beta-endorphin, which may be arising from a peripheral source. Intravenous beta-endorphin increases plasma glucose and delays the onset of hypoglycaemia following insulin but does not result in significant inhibition of the ACTH and cortisol response. This may reflect the poor penetration of beta-endorphin into the central nervous system, although a hypothalamic effect of beta-endorphin is implied by the increased PRL. The significantly delayed time course in ACTH and cortisol secretion noted during beta-endorphin is not explained by a later response of either CRH or AVP. Although peripheral levels of these hormones may be a relatively insensitive measure of hypothalamic function, an additional factor may influence ACTH release during hypoglycaemia.
业已证明，β-内啡肽可减少大鼠促肾上腺皮质激素释放激素（CRH）的生成及低血糖诱导的促肾上腺皮质激素（ACTH）分泌。我们旨在确定超生理水平的β-内啡肽是否会抑制人类受试者对胰岛素诱导的低血糖的ACTH和CRH反应。
在3小时内定期测量血浆葡萄糖、催乳素、皮质醇、ACTH、CRH和精氨酸加压素（AVP）。采用交叉设计，在30至90分钟内静脉输注5毫克/50毫升的β-内啡肽或等体积的生理盐水，并在60分钟时静脉注射0.15单位/千克的可溶性胰岛素。
6名年龄在20至35岁之间的健康男性志愿者。
采用荧光免疫分析法测量催乳素，采用放射免疫分析法测量ACTH、CRH和AVP，采用酶联免疫吸附测定法测量皮质醇。在采集每份血样之前记录血流动力学指标。结果以平均值±平均标准误表示。
β-内啡肽导致基线皮质醇显著降低（P<0.05），但对ACTH无影响。与生理盐水相比，在输注β-内啡肽期间，血浆葡萄糖（P<0.001）、CRH（P<0.05）和催乳素（P<0.05）显著升高。注射胰岛素后，在输注β-内啡肽和生理盐水期间，葡萄糖达到相似的最低点（分别为2.1±0.1和1.9±0.15毫摩尔/升），但在输注β-内啡肽期间血浆葡萄糖的下降延迟（方差分析，P<0.01）。这导致ACTH和皮质醇反应的时间进程显著改变（每项P<0.05），但反应幅度总体无差异。相比之下，CRH和AVP反应的时间和幅度均未受影响。注射胰岛素后催乳素也达到相似的峰值，而在输注β-内啡肽期间对低血糖的血流动力学反应无显著改变。
虽然已证明β-内啡肽对人类基础ACTH和皮质醇分泌具有抑制作用，但我们注意到，对β-内啡肽反应时血浆CRH显著增加，这可能源于外周来源。静脉注射β-内啡肽可增加血浆葡萄糖，并延迟胰岛素注射后低血糖的发作，但不会显著抑制ACTH和皮质醇反应。这可能反映出β-内啡肽进入中枢神经系统的渗透性较差，尽管催乳素升高暗示了β-内啡肽对下丘脑的作用。在输注β-内啡肽期间观察到的ACTH和皮质醇分泌时间进程显著延迟，并非由CRH或AVP的延迟反应所致。尽管这些激素的外周水平可能是下丘脑功能相对不敏感的指标，但可能有另一个因素影响低血糖期间的ACTH释放。
