Basal and adrenocorticotropin-stimulated corticosterone in the neonatal rat exposed to hypoxia from birth: modulation by chemical sympathectomy. Endocrinology 2004 Jan;145(1):79-86
Date
10/04/2003Pubmed ID
14525916DOI
10.1210/en.2003-1130Scopus ID
2-s2.0-0347719548 27 CitationsAbstract
We previously demonstrated that 7-d-old rat pups exposed to hypoxia from birth exhibit ACTH-independent increases in corticosterone associated with an increase in steroidogenic acute regulatory (StAR) and peripheral-type benzodiazepine receptor (PBR) proteins. The purpose of the present study was to determine whether this increase in corticosterone could be attenuated by chemical sympathectomy induced with guanethidine treatment. Rat pups were exposed to normoxia or hypoxia from birth and treated with vehicle or guanethidine and studied at 7 d of age. Hypoxia per se resulted in an increase in plasma corticosterone without a change in plasma ACTH. Guanethidine treatment attenuated the increase in basal corticosterone in hypoxic pups but did not attenuate ACTH-stimulated corticosterone production. This effect was specific as basal and ACTH-stimulated aldosterone was not affected. Guanethidine also attenuated the increase in StAR protein induced by hypoxia. Neither the effect of hypoxia nor that of guanethidine could be explained by changes in the levels of adrenal tyrosine hydroxylase, StAR, or P450scc mRNA, adrenal tyrosine hydroxylase immunohistochemistry, or adrenal catecholamine content. We conclude that chemical sympathectomy normalizes basal corticosterone levels but has no effect on ACTH-stimulated corticosterone levels in 7-d-old rats exposed to hypoxia from birth. The mechanism of the effect of guanethidine to normalize hypoxia-stimulated basal corticosterone remains to be identified, although StAR protein may be an important mediator. This ACTH-independent increase in corticosterone may be a mechanism by which the neonate can increase circulating glucocorticoids necessary for survival while bypassing the hyporesponsiveness of the neonatal hypothalamic-pituitary-adrenal axis.
Author List
Raff H, Lee JJ, Widmaier EP, Oaks MK, Engeland WCAuthor
Hershel Raff PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adrenal GlandsAdrenocorticotropic Hormone
Aldosterone
Animals
Animals, Newborn
Body Weight
Carrier Proteins
Catecholamines
Cholesterol Side-Chain Cleavage Enzyme
Corticosterone
Female
Guanethidine
Hypoxia
Phosphoproteins
Pregnancy
Rats
Rats, Sprague-Dawley
Receptors, GABA
Receptors, GABA-A
Renin
Reverse Transcriptase Polymerase Chain Reaction
Sympathectomy, Chemical
Sympatholytics
Tyrosine 3-Monooxygenase
