THE EFFECT OF BETA-ENDORPHIN ON BASAL AND INSULIN-HYPOGLYCEMIA STIMULATED LEVELS OF HYPOTHALAMIC-PITUITARY-ADRENAL AXIS HORMONES IN NORMAL HUMAN-SUBJECTS

OBJECTIVE It has been demonstrated that beta-endorphin reduces CRH pro duction and hypoglycaemia-induced ACTH secretion in the rat. We aimed to determine whether supraphysiological levels of beta-endorphin inhib it the ACTH and CRH response to insulin-induced hypoglycaemia in human subjects. DESIGN Plasma glucose, prolactin, cortisol, ACTH, CRH and A VP were measured at intervals over a 3-hour period. Intravenous beta-e ndorphin 5 mg/50 ml or an equal volume of normal saline was infused be tween 30 and 90 minutes, with soluble insulin 0.15 units/kg administer ed i.v. at 60 minutes in a cross-over design. SUBJECTS Six healthy mal e volunteers aged 20-35 years. MEASUREMENTS Prolactin was measured by a fluoroimmunometric assay, ACTH, CRH and AVP by radioimmunoassay, and cortisol was measured by enzyme-linked immunosorbent assay. Haemodyna mic measurements were recorded prior to each blood sample. Results are expressed as mean +/- standard error of the mean. RESULTS beta-Endorp hin 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 no rmal saline. After insulin administration, glucose reached a similar n adir 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 signific antly altered time-course for the ACTH and cortisol responses (P < 0.0 5 for each), but no difference overall in the magnitude of the respons e. In contrast, neither the timing nor the magnitude of the CRH and AV P 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 . CONCLUSIONS While beta-endorphin has been shown to be inhibitory to basal ACTH and cortisol secretion in humans, we note a significant inc rease in plasma CRH in response to beta-endorphin, which may be arisin g from a peripheral source. Intravenous beta-endorphin increases plasm a glucose and delays the onset of hypoglycaemia following insulin but does not result in significant inhibition of the ACTH and cortisol res ponse. This may reflect the poor penetration of beta-endorphin into th e central nervous system, although a hypothalamic effect of beta-endor phin is implied by the increased PRL. The significantly delayed time c ourse in ACTH and cortisol secretion noted during beta-endorphin is no t explained by a later response of either CRH or AVP. Although periphe ral levels of these hormones may be a relatively insensitive measure o f hypothalamic function, an additional factor may influence ACTH relea se during hypoglycaemia.