Activation of the hypothalamic-pituitary axis in adrenalectomised rats: Potentiation by chronic stress

The influence of chronic stress on the status of the hypothalamo-pituitary- adrenal (HPA) axis of sham-operated and adrenalectomised rats was assessed, Animals underwent bilateral adrenalectomy (ADX) and 3 days later they were either left undisturbed or subjected daily to immobilization for 2 h each morning for 14 days (chronic IMO). In situ hybridization histochemistry rev ealed that ADX increased corticotropin-releasing factor (CRF) mRNA levels i n the paraventricular nucleus of the hypothalamus (PVN) and proopiomelanoco rtin (POMC) mRNA levels in the anterior pituitary, in both control and chro nically stressed rats as measured on the day following the last exposure to stress. Chronic IMO increased CRF mRNA levels in the PVN and POMC mRNA lev els in the anterior pituitary of sham-operated rats, as measured on the day following the last exposure to stress. Chronic IMO potentiated the increas e in CRF mRNA in the PVN following ADX and resulted in further increases in CRF mRNA above levels seen in adrenal-intact animals. Finally, chronic str ess, while not altering basal ACTH levels of ADX rats, reduced the ACTH res ponse of these animals to a novel stressor (tail-shock for 30 min). These r esults suggest that chronic stress exerts a stimulatory influence at the hy pothalamic level that is partially restrained by daily stress-induced gluco corticoid release. Despite the potentiation by chronic stress of CRF mRNA c ontent in the PVN of ADX rats, a blunted circulating ACTH response to an ac ute short-term stressor was apparent in ADX-chronically stressed rats, sugg esting that chronic stress might also alter POMC processing and/or ACTH sec retory patterns in the anterior pituitary in ADX animals. (C) 1999 Elsevier Science B.V. All rights reserved.