Evidence for Acute ACTH Release by Extrahypothalamic Mechanisms1

In a previous report it was shown that prior manipulation “sensitized” rats bearing hypothalamic lesions so that the injection of extracts of nonhypothalamic tissue triggered rapid increases in plasma corticosterone. The purpose of the present study was to determine whether an endogenous ACTH-releasing mechanism accounts for this breakthrough and whether or not hypothalamic or extrahypothalamic pathways are involved. Therefore, laparotomy was used as a triggering stimulus instead of tissue extract injection and the influence of prior manipulation (ether stress and/or blood withdrawal) on the effect of this stimulus was examined. Laparotomy alone did not significantly increase plasma corticosterone levels in rats bearing ventral hypothalamic lesions. However, prior ether stress and/or blood withdrawal “sensitized” the lesioned rats and laparotomy, under these conditions, evoked increased plasma corticosterone levels. To determine whether the response to prior ether, blood withdrawal, and laparotomy was mediated via residual hypothalamus, these stimuli were applied to rats bearing expanded lesions which destroyed virtually all hypothalamic tissue. The response, although attenuated, was not abolished. Removal of all brain tissue anterior to the mesencephalon (pituitary isolation) did not eliminate circulating plasma corticosterone 6 hours postoperatively. The stress of blood withdrawal plus laparotomy in rats with pituitary islands evoked significant increases in plasma corticosterone. The observations of rapid stress-induced increases in plasma corticosterone in rats bearing ventral hypothalamic lesions, expanded hypothalamic lesions and pituitary islands provide evidence for the existence of extrahypothalamic pathways for acute ACTH release in rats. (Endocrinology90: 1160, 1972)