The Effect of High Dose Total Body Irradiation on ACTH, Corticosterone, and Catecholamines in the Rat

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