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Herein, we aimed at examining the therapeutic effects of 5-androstenediol (5-AED), a natural hormone produced in the adrenal cortex, on radiation-induced myelosuppression in C3H/HeN mice. The mice were subjected to whole-body irradiation with a sublethal dose of 5 Gy gamma-irradiation to induce severe myelosuppression, and 5-AED (50 mg/kg) was administered subcutaneously. 5-AED was administrated 1 day before irradiation (pre-treatment) or twice weekly for 3 weeks starting from 1 h after irradiation (post-treatment). Treatment with 5-AED significantly ameliorated the decrease in the peripheral blood neutrophil and platelet populations in irradiated myelosuppressive mice, but had no effect on the lymphocyte population. It also ameliorated hypocellularity and disruption of bone marrow induced by irradiation and led to rapid recovery of myeloid cells. Further, it attenuated the decrease in spleen weight and megakaryocyte and myeloid cell populations in the spleen and promoted multilineage hematopoietic recovery. We found that a single injection of 5-AED produced only a temporary therapeutic effect, while sequential injection of 5-AED after irradiation had a more pronounced and prolonged therapeutic effect and reduced myelosuppression by irradiation. Thus, sequential injection of 5-AED after irradiation has therapeutic potential for radiation-induced myelosuppression when administered continuously and can be a significant therapeutic candidate for the management of acute radiation syndrome, particularly in a mass casualty scenario where rapid and economic intervention is important.

Ionizing radiation can damage the hematopoietic system, and treatment with cytokines, including granulocytecolony-stimulating factor (G-CSF), is used to enhance hematopoietic recovery. In the present study, mice were whole-body irradiated with a sublethal dose of 5 Gy to produce severe myelosuppression and to evaluate the hematologic consequences of G-CSF treatment following irradiation. G-CSF (100 μg/kg of body weight) was injected immediately after irradiation, and then every three days for 3 weeks. G-CSF significantly ameliorated the decrease in peripheral neutrophils typically observed after exposure to radiation, but it also aggravated the decrease in the number of peripheral platelets during days 3–14 following irradiation. In the histological analysis, while the number of megakaryocytes was significantly decreased in the bone marrow, a number of trapped megakaryocytes were observed in the spleen of G-CSF-treated and irradiated mice. These data suggest that radiation-induced thrombocytopenia is worsened by G-CSF administration, possibly due to a decrease in the number of megakaryocytes in the bone marrow and an increase in the trapping of megakaryocytes in the spleen.