Stressor-specific activation of the hypothalamic-pituitary-adrenocortical axis.
New information has accrued from in vivo microdialysis studies about stress-related changes in norepinephrine concentrations in extracellular fluid of the paraventricular nucleus (PVN) and the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Our data on the effects of lower brainstem hemisections show that paraventricular noradrenergic terminals are derived mainly from medullary A1 and A2 catecholaminergic cells. The activation of these cells contributes importantly to stress-induced noradrenergic activation in the paraventricular nucleus of conscious animals. The results from brainstem hemisection experiments also indicate that baseline levels and immobilization-induced increments in corticotropin-releasing hormone (CRH) mRNA expression in the PVN depend on ipsilaterally ascending medullary tract. Thus, the prevalent concept that stress-induced noradrenergic activation of the HPA axis depends mainly on activation of locus ceruleus noradrenergic neurons requires re-evaluation. Our new stress concepts favor stressor-specific activation of the HPA axis. The present data also suggest the existence of stressor-specific central pathways that differentially participate in the regulation of sympathoneuronal and adrenomedullary outflows as well as of the activity of the HPA axis. Furthermore, the results are inconsistent with a founding tenet of Selye's stress theory, the doctrine of nonspecificity, which defines stress as the nonspecific response of the body to any demand. We expect that future studies in this area will focus on further examination of the notion of stressor-specific patterns of central neurotransmitter release and elucidate the genetic bases of these patterns.
Pacák
K
K
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke and Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryl.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D009490:Neurosecretory Systems / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*
D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine