Acute-stress-induced facilitation of the hypothalamic-pituitary-adrenal axis

It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis responds to a stressor by secreting facilitatory and inhibitory factors. D uring a stressor, the relative magnitude of secretion of these factors dete rmines the responsiveness of the HPA axis to a subsequent stressor. Previou s studies have suggested that corticosterone (B) secreted during the first stressor is an inhibitory factor. We hypothesized that the transient remova l of the inhibitory factor, B, during the first stressor would result in th e secretion of only facilitatory factors. This would cause the HPA axis to exist in a state of hyperresponsiveness, and to hypersecrete corticotropin (ACTH) and B in response to a second stressor. Therefore, our primary objec tive was to demonstrate stress-induced facilitation of the HPA axis respons e to a subsequent stressor. Male Sprague-Dawley rats were subjected to a 1- hour physical immobilization stressor (IMM) or administered a single dose o f ACTH on day 1. B response during these treatments was markedly but transi ently attenuated with an 100 mg/kg i.p. dose of aminoglutethimide (AG). Twe nty-four hours later, rats were subjected to an intraperitoneal saline inje ction stressor. B and ACTH levels were measured 15 min after the injection stressor. Rats treated with AG plus IMM on day 1 hypersecreted B and ACTH a fter the injection stressor on day 2. These results suggest that immobiliza tion stress induces facilitation of both pituitary and adrenal responses. E xogenous administration of ACTH- to AG-pretreated rats on day 1, in lieu of immobilization stress, did not affect the responsiveness of the HPA axis o n day 2. This suggests that ACTH secreted during the first stressor does no t play an important role in acute-stress-induced facilitation. Copyright (C ) 2000 S. Karger AG, Basel.