title: The effect of beta-endorphin on basal and insulin-hypoglycaemia stimulated levels of hypothalamic-pituitary-adrenal axis hormones in normal human subjects.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Six healthy male volunteers aged 20-35 years.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, Christchurch Hospital, University of Otago, New Zealand.
authors.forename: W J
authors.initials: WJ
authors.lastname: Inder
authors.forename: J H
authors.initials: JH
authors.lastname: Livesey
authors.forename: M J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: M J
authors.initials: MJ
authors.lastname: Evans
authors.forename: R A
authors.initials: RA
authors.lastname: Donald
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D001127:Arginine Vasopressin / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology; D011388:Prolactin / Q000097:blood; D013997:Time Factors; D001615:beta-Endorphin / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D001127:Arginine Vasopressin; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone