Glucocorticoid feedback control of corticotropin in the hypoxic neonatal rat. J Endocrinol 2007 Feb;192(2):453-8
Date
02/07/2007Pubmed ID
17283245Pubmed Central ID
PMC1832161DOI
10.1677/JOE-06-0103Scopus ID
2-s2.0-33947396870 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
The objective of this study was to determine the effects of manipulating glucocorticoid negative feedback on acute ACTH and corticosterone responses to corticotropin-releasing hormone (CRH) injection in 7-day-old rats exposed to normoxia or hypoxia from birth. Chemical adrenalectomy was achieved with aminoglutethimide, and glucocorticoids were replaced with a low dose of dexamethasone. Hypoxia per se increased basal plasma corticosterone and attenuated the plasma ACTH response to CRH. Aminoglutethimide per se decreased plasma corticosterone and strongly increased basal plasma ACTH and anterior pituitary POMC gene expression. Dexamethasone partially attenuated elevations in basal plasma ACTH due to aminoglutethimide in both normoxic and hypoxic pups, but inhibited anterior pituitary POMC expression and CRH-induced plasma ACTH only in hypoxic pups. Despite this inhibition, hypoxic pups treated with both dexamethasone and aminoglutethimide still exhibited a significant CRH-induced increment in plasma ACTH, which was lacking in hypoxic pups not treated with either dexamethasone or aminoglutethimide. We conclude that ACTH responses to acute stimuli in hypoxic neonatal rats are prevented by ACTH-independent increases in corticosterone, rather than by intrinsic hypothalamic-pituitary hypoactivity.
Author List
Raff H, Jacobson LAuthor
Hershel Raff PhD Professor in the Academic Affairs department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adrenergic AgentsAdrenocorticotropic Hormone
Aminoglutethimide
Animals
Animals, Newborn
Corticosterone
Corticotropin-Releasing Hormone
Dexamethasone
Feedback, Physiological
Glucocorticoids
Hypoxia
Pituitary Gland, Anterior
Pro-Opiomelanocortin
Rats
Rats, Sprague-Dawley
Receptors, Corticotropin-Releasing Hormone
Stimulation, Chemical