It has been hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis responds to a stressor by secreting facilitatory and inhibitory factors. During a stressor, the relative magnitude of secretion of these factors determines the responsiveness of the HPA axis to a subsequent stressor. Previous studies have suggested that corticosterone (B) secreted during the first stressor is an inhibitory factor. We hypothesized that the transient removal of the inhibitory factor, B, during the first stressor would result in the 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 objective was to demonstrate stress-induced facilitation of the HPA axis response to a subsequent stressor. Male Sprague-Dawley rats were subjected to a 1-hour physical immobilization stressor (IMM) or administered a single dose of ACTH on day 1. B response during these treatments was markedly but transiently attenuated with an 100 mg/kg i.p. dose of aminoglutethimide (AG). Twenty-four hours later, rats were subjected to an intraperitoneal saline injection 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 after the injection stressor on day 2. These results suggest that immobilization stress induces facilitation of both pituitary and adrenal responses. Exogenous administration of ACTH- to AG-pretreated rats on day 1, in lieu of immobilization stress, did not affect the responsiveness of the HPA axis on day 2. This suggests that ACTH secreted during the first stressor does not play an important role in acute-stress-induced facilitation.

Keywords:
Corticotropin, Adrenal steroids, Stress
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