Blunted pituitary-adrenocortical stress response in adult rats following neonatal dexamethasone treatment

Glucocorticoids have a prominent impact on the maturation of the stress-rel ated neuroendocrine system and on the postnatal establishment of adaptive b ehaviour. The present study aimed at investigating the stress responsivenes s of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, d examethasone. Newborn male Wistar rats were injected s.c. with 1 mu g/g dex amethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic ho rmone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pi tuitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 mu g/kg corticotropin releasing hormone (CRH). In addit ion, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capaci ties were assessed in the pituitaries of adult rats. The results showed tha t at day 10 basal ACTH concentration was elevated while the cold stress-evo ked ACTH response was attenuated in the dexamethasone-treated rats. As adul ts, treated rats showed a suppressed elevation of both ACTH and corticoster one plasma cncentrations in response to restraint, while basal hormonal con centrations were not altered. There was no difference in the magnitude of t he CRH-induced elevation of ACTH and corticosterone concentrations initiall y; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituita ry GR binding capacity. Neonatal dexamethasone treatment strongly suppresse d body weight gain, and adrenal and thymus weights in the early phase of po stnatal development. By adulthood, the body and adrenal weights were normal ized while thymus weight was greater than in controls. These findings indic ate that neonatal dexamethasone treatment permanently alters HPA axis activ ity by reducing stress responses to cold and restraint probably through sup ra-pituitary actions, and by decreasing the effectiveness of feedback throu gh a diminished GR binding in the pituitary.