The effect of androstanes on granulopoiesis in vitro and in vivo.
Bone marrow culture in a patient with aplastic anaemia responding to anabolic steroid (methandienone) therapy, showed an unusually high degree of growth in unstimulated cultures. Growth in unstimulated cultures is due to factors with colony stimulating activity (CSA) released by monocyte macrophages in the bone marrow sample. These cells, which can be identified by staining for non-specific esterase activity, were not increased in this patient's marrow, implying either increased production of colony stimulating factors or increased sensitivity to these factors. Addition of methandienone or testosterone to feeder-layers containing normal peripheral blood leucocytes increased their stimulatory activity. Addition of these drugs to feeder-layers of CSF-containing conditioned medium did not have this effect, implying that androstanes cause increased production of colony stimulating factors rather than increased sensitivity to them. Lack of response to androstane therapy may be related to lack of response by bone marrow monocyte macrophages or to the inability of granulopoietic cells to respond to the increased CSF production induced by androstane therapy. A means of predicting lack of response is proposed.
D000731:Androstanes / Q000494:pharmacology*; D000741:Anemia, Aplastic / Q000188:drug therapy*; D001853:Bone Marrow / Q000187:drug effects*; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008696:Methandrostenolone / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects
D000731:Androstanes; D003115:Colony-Stimulating Factors; D008696:Methandrostenolone