The vasopressin-deficient Brattleboro rat: lessons for the hypothalamo-pituitary-adrenal axis regulation

Adaptation to stress is indispensable to life and the hypothalamo-pituitary-adrenocortical axis is one of the major components of the adaptation. The hypothalamic component consists of corticotropin-releasing hormone and arginine vasopressin, with a questionable contribution of the latter. Vasopressin was more important in the regulation of the adrenocorticotropin secretion in the perinatal vasopressin-deficient Brattleboro rats than in adulthood, where its role depended on the nature of the stressor encountered. In adults, the vasopressin deficiency did not influence the development of chronic stress response. In the neonatal rats, the role of vasopressin was supported by the inhibitory action of a V1b antagonist and vasopressin antiserum. As the corticosterone response to stress did not follow the adrenocorticotropin levels, we assume the presence of an adrenocorticotropin independent adrenal gland regulation in the neonates. We have shown that the apparent dissociation of the corticosterone and adrenocorticotropin responses is not due to the different time course of the two hormone responses, to different level of the corticosterone binding globulin or to changes in the adrenal gland sensitivity. In vitro experiments point to the contribution of beta-adrenoceptors in the process. It was also confirmed by in vivo tests using the vasopressin-deficient Brattleboro pup as a model organism, where corticosterone levels may rise without adrenocorticotropin level changes. Another important question is the role of adrenocorticotropin beyond the corticosterone secretion regulation, which could be supposed, e.g., in cardiovascular events, immunological processes, and metabolism. We can conclude that Brattleboro rats gave us much information about the stress-axis regulation far beyond the role of vasopressin itself.