Regulation of activity in the hypothalamo-pituitary-adrenal axis is integral to a larger hypothalamic system that determines caloric flow.

We have previously reported that there are diurnal rhythms in the magnitude of ACTH responses to stressors and in the sensitivity of stress-induced ACTH responses to facilitation induced by prior stress and to corticosterone (B) feedback induced by exogenous B. In all cases ACTH was more responsive in the morning than in the evening in nocturnally feeding rats. We have also shown in adrenalectomized rats that an overnight fast reduces ACTH responses to restraint in the morning compared with rats fed ad libitum, and we have shown that calorie-containing gavage during the fast increases the amplitude of ACTH responses to restraint in fasted rats. Therefore, this diurnal rhythm is not associated with B feedback and is associated with calories. In these studies we asked whether young, male intact rats that were deprived of food overnight had: 1) hypothalamo-pituitary-adrenal (HPA) axis responses during the fasting period; 2) altered basal activity in the HPA axis; 3) altered responsivity of ACTH to restraint; and 4) altered sensitivity of restraint-induced ACTH responses to facilitation or B feedback. Our results show that food deprivation: 1) induces marked ACTH and B responses during the fast that mirrors the pattern of food intake in fed rats, with an approximately 3-h lag; 2) results in essentially no change in basal ACTH in the morning; 3) reduces ACTH responsivity to stress in the morning; and 4) reduces ACTH responsivity to prior stress-induced facilitation and exogenous B-induced feedback. We conclude that: 1) the HPA axis serves as a default pathway to feeding when food is not available; 2) the diurnal rhythms in restraint-induced ACTH secretion are determined by food intake; and 3) the HPA axis is integral to a larger hypothalamic system that mediates energy flow.