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Effect of high-dose total body irradiation on ACTH, corticosterone, and catecholamines in the rat. Transl Res 2011 Jan;157(1):38-47

Date

12/15/2010

Pubmed ID

21146149

Pubmed Central ID

PMC3053012

DOI

10.1016/j.trsl.2010.09.007

Abstract

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic-pituitary-adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study assessed HPA axis function in rats undergoing TBI. Using a head-shielded model of TBI, we found an enhanced response to corticotropin-releasing hormone (CRH) in vitro in pituitaries from irradiated compared with nonirradiated rats at both 8 and 70 days after 10-Gy single fraction TBI. At 70, but not 8 days, plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels were increased significantly in irradiated compared with nonirradiated rats. Plasma aldosterone was not affected by TBI at either time point, whereas plasma renin activity was decreased in irradiated rats at 8 days. Basal and stimulated adrenal steroid synthesis in vitro was not affected by TBI. In addition, plasma epinephrine was decreased at 70 days after TBI. The hypothalamic expression of CRH messenger RNA (mRNA) and hippocampal expression of glucocorticoid receptor mRNA were unchanged by irradiation. We conclude that the hypertension of radiation nephropathy is not aldosterone or catecholamine-dependent but that there is an abscopal activation of the HPA axis after 10 Gy TBI. This activation was attributable at least partially to enhanced pituitary ACTH production.

Author List

Cohen EP, Bruder ED, Cullinan WE, Ziegler D, Raff H

Authors

William E. Cullinan PhD Adjunct Associate Professor in the Neurosurgery department at Medical College of Wisconsin
Hershel Raff PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adrenocorticotropic Hormone
Aldosterone
Animals
Catecholamines
Corticosterone
Corticotropin-Releasing Hormone
Cytochrome P-450 Enzyme System
Gene Expression Regulation
Humans
Male
Nuclear Warfare
Pro-Opiomelanocortin
RNA, Messenger
Radiation Dosage
Radioactive Hazard Release
Rats
Rats, Inbred Strains
Receptors, Glucocorticoid
Receptors, LDL
Renin
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Terrorism
Tyrosine 3-Monooxygenase
Whole-Body Irradiation
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d