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Blunted pituitary-adrenocortical stress response in adult rats following neonatal dexamethasone treatment.
J Neuroendocrinol 2000; 12(10):1014-21JN

Abstract

Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 microg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (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, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 microg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma concentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary.

Authors+Show Affiliations

Central Research Department, Semmelweiss University, Faculty of Health Sciences, Budapest, Hungary. kfelsz@lib.hiete.huNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11012843

Citation

Felszeghy, K, et al. "Blunted Pituitary-adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone Treatment." Journal of Neuroendocrinology, vol. 12, no. 10, 2000, pp. 1014-21.
Felszeghy K, Bagdy G, Nyakas C. Blunted pituitary-adrenocortical stress response in adult rats following neonatal dexamethasone treatment. J Neuroendocrinol. 2000;12(10):1014-21.
Felszeghy, K., Bagdy, G., & Nyakas, C. (2000). Blunted pituitary-adrenocortical stress response in adult rats following neonatal dexamethasone treatment. Journal of Neuroendocrinology, 12(10), pp. 1014-21.
Felszeghy K, Bagdy G, Nyakas C. Blunted Pituitary-adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone Treatment. J Neuroendocrinol. 2000;12(10):1014-21. PubMed PMID: 11012843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blunted pituitary-adrenocortical stress response in adult rats following neonatal dexamethasone treatment. AU - Felszeghy,K, AU - Bagdy,G, AU - Nyakas,C, PY - 2000/9/30/pubmed PY - 2001/2/28/medline PY - 2000/9/30/entrez SP - 1014 EP - 21 JF - Journal of neuroendocrinology JO - J. Neuroendocrinol. VL - 12 IS - 10 N2 - Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 microg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (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, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 microg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma concentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. SN - 0953-8194 UR - https://www.unboundmedicine.com/medline/citation/11012843/Blunted_pituitary_adrenocortical_stress_response_in_adult_rats_following_neonatal_dexamethasone_treatment_ L2 - https://doi.org/10.1046/j.1365-2826.2000.00551.x DB - PRIME DP - Unbound Medicine ER -