• L Q Stewart, J A Roper, W S Young, A-M O'Carroll, and S J Lolait.
• Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), University of Bristol, Bristol, UK.
• J. Neuroendocrinol. 2008 May 1; 20 (5): 597-605.

AbstractArginine vasopressin and corticotrophin-releasing hormone synthesised and released from the hypothalamic paraventricular nucleus are the prime mediators of the hypothalamic-pituitary-adrenal (HPA) axis response to stress. These neurohormones act synergistically to stimulate adrenocorticotophin (ACTH) secretion from the anterior pituitary, culminating in an increase in circulating glucocorticoids. Arginine vasopressin mediates this action at the arginine vasopressin 1b receptor (Avpr1b) located on pituitary corticotrophs. Arginine vasopressin is regarded as a minor ACTH secretagogue in rodents but evidence suggests that it has a role in mediating the neuroendocrine response to some acute and chronic stressors. To investigate the role of the Avpr1b in the HPA axis response to an acute and chronic (repeated) stress, we measured the plasma ACTH and corticosterone concentrations in three stress paradigms in both Avpr1b knockout and wild-type mice. Single acute exposure to restraint, forced swim and change in environment stressors elevated both plasma ACTH and corticosterone concentrations in wild-type animals. Conversely, the ACTH response to the acute stressors was significantly attenuated in Avpr1b knockout mice compared to their wild-type counterparts. Plasma corticosterone concentrations were reduced in Avpr1b knockout mice in response to change in environment but not to mild restraint or forced swim stress. Irrespective of genotype, there was no difference in the plasma ACTH or corticosterone concentrations in response to acute and repeated stressors. The data show that a functional Avpr1b is required for an intact pituitary ACTH response to the acute and chronic stressors used in this study. Furthermore, the normal corticosterone response to repeated exposure to change in environment stress also requires the Avpr1b to drive HPA axis responsiveness.

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