Regulation of Pituitary Vasopressin Receptors during Chronic Stress: Relationship to Corticotroph Responsiveness

The relationship between vasopressin (VP) receptor levels in the anterior pituitary and VP-stimulated ACTH release in vitro was studied in rats subjected to various chronic stress paradigms. The stress models used were water deprivation for 60 h and administration of 2% NaCI in the drinking water (both of which are associated with decreased pituitary ACTH responsiveness), and repeated i.p.hypertonic saline injections or repeated daily immobilization for 14 days (associated with increased ACTH responsiveness to novel stimuli). VP receptors were measured by binding of ³H]arginine-VP to anterior pituitary membrane-rich fractions, and ACTH responses to VP in collagenase dispersed anterior pituitary cells. In control rats, binding of ³H]AVP was saturable and high affinity, with a Kd of 0.45 ± 0.05 nM and a B_max of 138.8 ± 8.1 fmol/mg. In pituitary membranes from stressed rats, binding affinity was unchanged, but B_max changed according to the type of stress. While VP binding was markedly reduced after water deprivation and 2% saline (25% and 49%, respectively), it was significantly increased after repeated i.p. hypertonic saline injections and repeated immobilization (126% and 154% of controls, respectively). The changes in VP binding were associated to parallel changes in maximum VP-stimulated ACTH production in vitro, with a 34% decrease in water deprived rats and a 25% increase in hypertonic saline injected rats. The potentiating effect of VP on corticotropin releasing hormone-stimulated ACTH was also reduced in cells from water-restricted rats, and increased in cells from rats given repeated injections of hypertonic saline. The data show a direct relationship between changes in corticotroph responsiveness and changes in pituitary VP receptors during chronic stress, suggesting that pituitary VP receptor regulation is involved in the adaptation of the HPA axis during chronic stress.