Effect of high-dose total body irradiation on ACTH, corticosterone, and catecholamines in the rat

Abstract

Total 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 can result in injury to multiple tissues and may result in death due to multi-organ 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, due to hypertension and uremia. The present study assessed HPA axis function in rats undergoing total body irradiation (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 to non-irradiated rats at both eight and seventy days after 10 Gy single fraction TBI. At seventy, but not eight days, plasma ACTH and corticosterone levels were significantly increased in irradiated compared to non-irradiated rats. Plasma aldosterone was not affected by TBI at either time point, while 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. Hypothalamic expression of CRH 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 at least partially attributable to enhanced pituitary ACTH production.

Neonatal overfeeding disrupts pituitary ghrelin signalling in female rats long-term; Implications for the stress response

“…We next examined whether neonatal overfeeding similarly suppresses ACTH production in response to stimulation with CRH, the main stimulator of ACTH secretion. Stimulation with CRH increased ACTH production as compared to baseline levels and as previously shown in studies using similar protocols to assess CRH-stimulated ACTH production in vitro [ 54 , 55 ]. There were no further post hoc differences between fractions or experimental groups (within-subjects significant effect of time: F (3,21) = 2.96, p = 0.056; n = 4–5; Fig 5G ), and no differences were revealed in the AUC analysis ( Fig 5H ).…”

Relationship between locomotor activity rhythm and corticosterone levels during HCC development, progression, and treatment in a mouse model

“…The additional stress induced by radiotherapy further heats up the proinflammatory response leading to a vicious circle 48,49 . Rats exposed to 1‐10 Gy irradiation showed a significant increase in the plasma corticosterone levels as compared with non‐irradiated rats 49,50 . Consistently, in this study, the serum corticosterone levels were significantly increased in tumor + irradiated group as compared with the tumor group, especially after irradiation at ZT08 and ZT20 reflecting increased chronic stress and/or neuroinflammation.…”

“…48,49 Rats exposed to 1-10 Gy irradiation showed a significant increase in the plasma corticosterone levels as compared with non-irradiated rats. 49,50 Consistently, in this study, the serum corticosterone levels were significantly increased in tumor + irradiated group as compared with the tumor group, especially after irradiation at ZT08 and ZT20 reflecting increased chronic stress and/or neuroinflammation. The number of p-ERK immunoreactive cells in the SCN was significantly increased in mice which received radiotherapy at ZT20.…”

Irradiation of the kidneys causes pathologic remodeling in the nontargeted heart: A role for the immune system

“…Suppression of the RAAS system using ACE inhibitors and AT1 blockers mitigates radiation‐induced renal injury. However, hypertension of radiation nephropathy is not aldosterone dependent, 40 with no clear evidence to date of activation of the RAAS system upon irradiation of kidney in WAG/RijCmcr rats 41 …”