Ultraviolet B irradiation of the mouse eye induces pigmentation of the skin more strongly than does stress loading, by increasing the levels of prohormone convertase 2 and α-melanocyte-stimulating hormone.

BACKGROUND: In previous studies, we made the unexpected finding that in mice, ultraviolet (UV)B irradiation of the eye increased the concentration of α-melanocyte-stimulating hormone (α-MSH) in plasma, and systemically stimulated epidermal melanocytes. AIMS: To compare the extent of the pigmentation induced by social and restraint stress (which activate the hippocampus-pituitary system) with that induced by UVB irradiation. METHODS: DBA/2 and sham-operated or hypophysectomized DBA/2 mice were subjected to local UVB exposure using a sunlamp directed at the eye, and two types of stress (social and restraint) were imposed. RESULTS: UVB irradiation of the eye or exposure to stress loading both increased the number of Dopa-positive melanocytes in the epidermis, and hypophysectomy strongly inhibited the UVB-induced and stress-induced stimulation of melanocytes. Irradiation of the eye caused a much greater increase in dopamine than did the stress load. Both UVB eye irradiation and stress increased the blood levels of α-MSH and adrenocorticotropic hormone (ACTH). In addition, the increase in plasma α-MSH was greater in animals subjected to UVB eye irradiation than in those subjected to stress loading, whereas the reverse occurred for plasma ACTH. UVB irradiation to the eye and stress loading increased the expression of prohormone convertase (PC)1/3 and PC2 in the pituitary gland. The increase in expression of pituitary PC2 was greater in animals subjected to UVB eye irradiation than to stress, whereas no difference was seen between the two groups for the increase in PC1/3. CONCLUSIONS: UVB eye irradiation exerts a stronger effect on pigmentation than stress loading, and is related to increased levels of α-MSH and PC2.

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

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.

Effect of a 50 Hz electric field on plasma ACTH, glucose, lactate, and pyruvate levels in stressed rats.

The effect of extremely low frequency electric field (EF) on stress induced changes of plasma ACTH, glucose, lactate, and pyruvate levels was examined in ovariectomized rats. The rats were exposed to 50 Hz EF (17500 V/m) for 60 min and were restrained for the latter half (30 min) of the EF exposure period. The restraint stress significantly increased the plasma ACTH and glucose levels (P <.05: Student's t test). Restraint induced increase of plasma ACTH and glucose levels tended to be suppressed by exposure to the EF. Meanwhile, the EF exposure also affected plasma lactate level. Thus, the EF exposure significantly decreases plasma lactate levels in the stressed rats (P <.05: Student's t test). Although the precise mechanisms in the restraint dependent alteration in plasma ACTH, glucose, lactate, and pyruvate levels are not fully understood, our results demonstrate that the 50 Hz EF alter both stress responses and energy metabolism in stressed rats.

Effect of heavy ions on neuro-endocrine regulations.

During American and Russian short and long-term space flights neuroimmune dysregulations have been observed in man and rats for up to three months after the return. During Extra-Vehicular Activity, radiation exposure risk is greater to elicit short and/or long-term deleterious effects on the functional capacity of the neuroimmune system. In order to assess the effects of high LET events on neuroimmune networks, our preliminary ground-based study was to investigate brain inflammatory responses in mouse after low dose radiation exposure with high LET particles (12C, 95MeV/u, 42 mGy). Plasma corticosterone levels were rapidly (6 hours) increased by two-fold, then decreased 24 hours post-irradiation. At 3 days plasma corticosterone and ACTH concentrations were also two- to three-fold increased. Plasma ACTH levels were still elevated up to seven days to two months. Furthermore immune functions are under current assessment. The results of this study should allow a greater understanding of the effects of high LET particles on neuroimmune system.

Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1 alpha.

Recombinant human interleukin-1 alpha (rhIL-1 alpha) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1 alpha in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1 alpha administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1 alpha-induced increase in ACTH levels at the doses used. In fact, the rhIL-1 alpha-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus.

[The coupling of the contrariwise changes in the steroid-secreting activity of the adrenals and the steroid-metabolizing activity of the liver in rats after x-ray irradiation]. / Sopriazhennost' protivonapravlennykh izmenenii steroidsekretiruiushchei aktivnosti nadpochechnikov i steroidmetaboliziruiushchei aktivnosti pecheni krys pri rentgenovskom obluchenii.

The rat adrenal cortex activation is accompanied by inhibition of steroid metabolism in liver and vice versa at acute radiation disease caused by X-ray irradiation. A coupling of contrary changes of corticosteroid secretion and metabolism evidences that there is common regulation of these functions. The possible ACTH participation in coupling of adrenals and liver functions and the liver role in radiation hypercorticism genesis are discussed.

[The early reaction of the neuroendocrine system to irradiation at high doses]. / Ranniaia reaktsiia neiroéndokrinnoi sistemy pri obluchenii v vysokikh dozakh.

It has been found that in 2 hours after the total gamma irradiation of rats at doses of 20 and 100 Gy the ACTH and glucagon levels in plasma increased by 5-6 and 10-12 times correspondingly. No significant changes in levels of plasma insulin and glucose have been revealed.

Effects of hypophysectomy and dexamethasone on rat adrenal response to microwaves.

Circulating corticosterone levels were measured to compare the adrenocortical response to acute microwave exposure of normal, hypophysectomized, or sham-hypophysectomized rats. Plasma corticosterone levels in acutely hypophysectomized rats exposed to 60 mW/cm2 for 60 min were below control levels, indicating that the microwave-induced corticosterone response observed in normal, intact rats is dependent on ACTH secretion by the pituitary. In other groups of rats pretreated with dexamethasone before being exposed to microwaves for 60 min, the corticosterone response to a 50-mW/cm2 exposure was completely suppressed by doses equal to or greater than 3.2 micrograms dexamethasone/100 g body weight. However, the corticosterone response to a 70-mW/cm2 exposure was only partially suppressed by prior administration of 3.2 or 5.6 micrograms dexamethasone/100 g BW. The evidence obtained in these experiments, in conjunction with the results of other experiments previously reported, is consistent with the hypothesis that the stimulation of the adrenal axis in the microwave-exposed rat is a systemic, integrative process due to a general hyperthermia.

Diurnal rhythm of the pituitary-adrenocortical response to stress: effect of constant light and constant darkness.

The existence of a biological rhythm in the response of animals to noxious stimuli and drugs is well known. However, the mechanism of this response is not well understood. This study was undertaken to describe the existence of a diurnal rhythm in the hypothalamic-pituitary-adrenocortical system before and after stress in female rats kept in controlled environmental conditions in 12L:12D, 24L:OD, or OL:24D. Plasma ACTH and plasma corticosterone concentrations were compared in unstressed animals. The time pattern in the response to stress was determined at four hourly intervals during a 24 hr period in which plasma ACTH and plasma corticosterone were measured at different time intervals. The stress response varied considerably with time of day in both magnitude and duration. The adrenals of rats exposed to constant light for 45 days atrophied, whereas the adrenals of animals kept in constant dark for the same period did not differ significantly from those of controls kept in 12L:12D. The increase in plasma ACTH in response to stress was greater both in the animals maintained in constant light and in constant dark than in the 12L:12D controls. Homeostatic mechanisms involved in these changes are discussed.