5-Androstene-3β,17β-diol promotes recovery of immature hematopoietic cells following myelosuppressive radiation and synergizes with thrombopoietin.
OBJECTIVE
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
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.
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Fatima S F
FS
Aerts-Kaya
Trudi P
TP
Visser
Shazia
S
Arshad
James
J
Frincke
Dwight R
DR
Stickney
Chris L
CL
Reading
Gerard
G
Wagemaker
D015114:Androstenediol / Q000494:pharmacology*; D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D001853:Bone Marrow; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D003114:Colony-Forming Units Assay; D019583:Dose Fractionation, Radiation; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013926:Thrombopoietin / Q000494:pharmacology; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000379:methods
D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin; D015114:Androstenediol