Stimulatory and inhibitory regulators of the hypothalamo–pituitary–adrenocortical axis

Short- and long-term metabolic effects of stress are mediated through the hypothalamo–pituitary–adrenocortical (HPA) axis and the sympathetic nervous system. While efficient functioning of these systems is essential for life processes, dysfunction can lead to hypercortisolaemia and inappropriately elevated catecholamines, resulting in immunosuppression and associated pathologies. This review will concentrate on the central mechanisms involved in the control of HPA axis activity, particularly neuronal, neuropeptide and transcriptional input to CRF and AVP expression in the hypothalamus. The emphasis of the article will be on our increased understanding of selective and specific responses of the HPA axis to different types of stressors. Elucidating the biochemical mechanisms underlying stress may permit the development of pharmacological strategies to treat chronic stress which exacts such a major toll on our quality of life today.