Acceleration of Granulopoietic Recovery by Androgenic Steroids in Mice Made Neutropenic by Cytotoxic Drugs1

Injection of testosterone, nortestosterone, or oxymetholone markedly enhanced granulopoietic recovery in mice made neutropenic by l,3-bis(2-chloroethyl)-l-nitrosourea, vinblastine, or cyclophosphamide. Blood neutrophils rose to six times normal counts, and the bone marrow showed sequential increases first in dividing granulocytic elements and later in the nondividing reserve. The steroid-induced increase in myeloblasts was preceded by an increase in in vitro colony-forming cells and colony-forming units. Mice whose spleen colonyforming units had been eradicated by busulfan failed to show a granulopoietic response to androgens. The relationship be tween colony-forming units and -forming cells is discussed, and it is suggested that the granulopoietic effect of steroids results from stimulation of the proliferation of unipotential, granulo cytic, colony-forming stem cells.