Congenital absence of vasopressin and age-dependent changes in ACTH and corticosterone stress responses in rats

Abstract

The hypothalamic components of the hypothalamo–pituitary–adrenal axis (HPA) are corticotropin-releasing hormone (CRH) and vasopressin. To test the hypothesis that HPA regulation changes with age, we compared ether and bacterial lipopolysaccharide (LPS) injection induced stress reactions in adult and 10-day-old Brattleboro rats, which naturally lack vasopressin owing to mutation of the gene (di/di). The LPS stimulus was used also with V_1b receptor antagonist pretreatment (SSR149415). In adult di/di or V_1b pretreated rats, we observed normal pituitary and adrenocortical secretory responses, while in all 10-day-old rats stress-induced serum corticosterone increases were marked, but adrenocorticotropin (ACTH) increases were significantly smaller. Compared to control pups the adenohypophysis of the 10-day-old di/di rats responded normally to CRH, but their adrenal glands were hyper-responsive to ACTH, while in adults there was greater secretion at both levels with no difference between the genotypes. The serum transcortin level was higher in adults than pups, with the di/di pups having higher transcortin levels than controls. Hence, using the same stressors in adults and pups with both a genetic model and pharmacological pretreatment, we have shown that the role of vasopressin in ACTH regulation is more important during the neonatal period than in adulthood. Blunted hypophysial sensitivity to CRH and similar adrenal gland sensitivity to ACTH in the pups compared to adults suggest that hypothalamic factors could be responsible for the neonatal stress hyporesponsive period.

Keywords::

• CBG
• corticosterone
• ether exposure
• LPS
• stress hyporesponsive period
• V_1b antagonist

Acknowledgements

Supported by grants F 48783, IN 67249 and NN 71629 from OTKA, Hungary and a grant 059/2006 from ETT, Hungary.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.