Hypothalamo-pituitary-adrenocortical dysregulation in aging F344/Brown-Norway F1 hybrid rats

Hypothalamo-pituitary-adrenocortical (HPA) axis aging was studied in young (3 mo), middle aged (15 mo) and aged (30 mo) F344/Brown Norway hybrid rats. This strain was selected to obviate HPA-relevant pathologies found in othe r aging models. Aged, unstressed rats showed enhanced central HPA drive, ma rked by elevated ACTH release and decreased pituitary proopiomelanocortin a nd corticotropin-releasing factor receptor 1 (CRH-R1) mRNAs. Acute corticos terone responses to spatial novelty were exacerbated in aged rats; however, responses to restraint or hypoxia were not affected. Chronic stress exposu re also differentially increased HPA drive in aged animals, marked by eleva ted paraventricular nucleus CRH peptide levels and pituitary proopiomelanoc ortin mRNA. Plasma ACTH and pituitary POMC and CRH-R1 mRNA expression in mi ddle-aged rats were intermediate those of young and aged animals. Middle-ag ed animals responded to chronic stress with disproportionate increases in C RH mRNA levels, and increased corticosterone secretion following hypoxia bu t not novelty. The results suggest a gradual increase in HPA tone across th e aging process, culminating in marked hyperresponsivity to both acute and chronic stress in senescence. (C) 2001 Published by Elsevier Science Inc. A ll rights reserved.