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  • Title: 5-Androstene-3β,17β-diol promotes recovery of immature hematopoietic cells following myelosuppressive radiation and synergizes with thrombopoietin.
    Author: Aerts-Kaya FS, Visser TP, Arshad S, Frincke J, Stickney DR, Reading CL, Wagemaker G.
    Journal: Int J Radiat Oncol Biol Phys; 2012 Nov 01; 84(3):e401-7. PubMed ID: 22672754.
    Abstract:
    PURPOSE: 5-Androstene-3β,17β-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. METHODS AND MATERIALS: BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. RESULTS: BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. CONCLUSIONS: 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO.
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