The effect of ovine corticotrophin-releasing factor on the hormonal response to insulin-induced hypoglycaemia

In order to investigate the role of hypothalamic corticotrophin-releasing factor (CRF41) in the mediation of the pituitary ACTH response to hypoglycaemia, eight normal adult males were studied on four occasions. Commencing at 0830 h after an overnight fast, each received, in double-blind, random order, intravenous boluses of: A, normal saline control; B, soluble insulin 0.15U/kg; C, ovine CRF41 (oCRF41) 100 μg; D, soluble insulin 0.15 U/kg followed immediately by oCRF41 100 μg. Adequate hypoglycaemia (blood glucose <2.2 mmol/l) was achieved in each subject when insulin was given alone or with oCRF41, and there was no difference in the glucose nadir between the 2 days. Peak plasma ACTH was significantly higher after insulin plus oCRF41 than after insulin alone (P <0.05) or oCRF41 alone (P <0.01) and this enhancement of ACTH release was most marked in the first phase of the response at 30 min (P <0.001, b vs d). There was no difference in the peak serum cortisol response whether oCRF41 and insulin were given alone or together and although the area under the cortisol curve was greater after insulin plus oCRF41, this difference was explicable simply on the basis of the earlier onset of the cortisol response to oCRF41. There were no differences in the serum GH responses to hypoglycaemia on the 2 days. We conclude that during the initial, rising phase of the ACTH response to hypoglycaemia, secretion of hypothalamic CRF41 is not maximally stimulated and that changes in ACTH release are mediated by changes in another hypothalamic factor, the action of which is enhanced by simultaneous administration of a maximal stimulating dose of oCRF41.