To study the possible involvement of hypothalamic corticotropin-releasing factor (CRF) in the stimulation of adrenocorticotropic hormone (ACTH) release caused by insulin-induced hypoglycemia (IIH), we measured CRF secretion in hypophysial portal blood (HPB) in rats anesthetized with sodium thiopental after injection of insulin. Before treatment, systemic ACTH levels (952 ± SE 143 pg/ml; n= 12) were well above normal values, probably reflecting the anesthetic and surgical stress consecutive to the preparation for portal blood collection. Insulin injection induced a significant increase of ACTH release within 15 min (1,588 ± 168 vs. 741 ± 144 pg/ml; n = 6, in vehicle-injected rats) which lasted for at least 1 h. CRF levels in HPB were 857 ± SE 168 pg/ml (n = 13) during the first-hour pretreatment collection. Vehicle injection did not modify CRF secretion (759 ± 142 pg/ ml; n = 6). Insulin injection provoked a significant increase in CRF release (1,449 ± 257 pg/ml; n = 7). These data suggest that an increased hypothalamic CRF secretion is responsible for the stimulation of pituitary ACTH release following IIH. The possible involvement of central neuromediators in the IIH-induced CRF production is discussed.

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