title: Neonatal glucocorticoid overexposure programs pituitary-adrenal function in ponies.
abstract: The present study tested the hypothesis that overexposure to endogenous glucocorticoids in neonatal life alters the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in ponies at 1 and 2 yr of age. Newborn foals received saline (0.9% NaCl, n = 8, control) or long-acting adrenocorticotropic hormone (ACTH1-24) (Depot Synacthen 0.125 mg intramuscularly twice daily, n = 9) for 5 d after birth to raise cortisol concentrations 5- to 6-fold. At 1 and 2 yr of age, HPA axis function was assessed by bolus administration of short-acting ACTH1-24 (1 μg/kg intravenous) and insulin (0.5 U/kg intravenous) to induce hypoglycemic on separate days. Arterial blood samples were taken at 5 to 30-min intervals before and after drug administration to measure plasma ACTH and/or cortisol concentrations. There were no differences in the basal plasma ACTH or cortisol concentrations or in the cortisol response to exogenous ACTH1-24 with neonatal treatment or age. At 1 and 2 yr of age, the increment in plasma ACTH but not cortisol at 60 min in response to insulin-induced hypoglycemia was greater in ponies treated neonatally with ACTH than saline (P < 0.05). Neonatal cortisol overexposure induced by neonatal ACTH treatment, therefore, alters functioning of the HPA axis in adult ponies.
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK. Electronic address: J.K.Jellyman.00@cantab.net.
authors.forename: J K
authors.initials: JK
authors.lastname: Jellyman
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: O A
authors.initials: OA
authors.lastname: Valenzuela
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: V L
authors.initials: VL
authors.lastname: Allen
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Forhead
authors.affiliation: Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: N B
authors.initials: NB
authors.lastname: Holdstock
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: A L
authors.initials: AL
authors.lastname: Fowden
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D003366:Cosyntropin / Q000008:administration & dosage / Q000494:pharmacology*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006736:Horses / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood; D010913:Pituitary-Adrenal System / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D003366:Cosyntropin; C006418:adrenocorticotropin zinc; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: ACTH; Adrenal; Cortisol; Glucocorticoid; Horse; Hypoglycemia; Pituitary