Studies of the Location of the Receptor Site for Negative Feedback Control of ACTH Release1

Abstract

Dexamethasone-21-phosphate was administered to rats 20 hr after graded amounts of forebrain had been removed. Four hr later, its ability to suppress ACTH release was estimated by measuring corticosterone in a 3-min collection of left adrenal effluent, obtained immediately after laparotomy under ether anesthesia. Corticosterone secretion was suppressed in dexamethasone-treated hypothalamic island and median eminence island animals as well as in dexamethasone-treated intact controls. Untreated animals of all groups had relatively high corticosterone secretion rates. Untreated animals with pituitary islands usually had pituitary infarcts and low corticosterone secretion rates, even without dexamethasone suppression. While the dexamethasone-treated pituitary island animals tended to have lower secretion rates than untreated pituitary island animals, it was not possible to assess with certainty the effect of dexamethasone on ACTH release in these animals. Since dexamethasone unequivocally suppressed ACTH secretion in animals with median eminence islands, it was concluded that none of the forebrain exclusive of the median eminence is essential to the mechanism whereby corticoids block stress-induced ACTH release in the rat. (Endocrinology74: 279, 1964)