Decreased erythroid colony-forming cell response of XTfm/Y mice to testosterone and 5 beta-dihydrotestosterone.
Although certain tissue of XTfm/Y mice are known to be deficient in androgen-binding sites, the defect has not been documented for bone marrow. To study the bone marrow response to testosterone and its metabolites, we compared the responses of the erythroid colony-forming cell (CFU-E) in these mice and their wild counter-parts, XTa/Y mice, using an in vitro methyl cellulose system in the presence of erythropoietin. Testosterone or 5 beta-dihydrotestosterone (5 beta-DHT) treatment (5 mg/kg) of Ta/Y mice in vivo before femoral bone marrow culture resulted in a significant increase in CFU-E colonies. However, similar in vivo treatment of Tfm/Y mice with testosterone or 5 beta-DHT had no effect on CFU-E colony formation. 5 alpha-DHT had no significant effect on Ta/Y or Tfm/Y mouse bone marrow. Testosterone or 5 beta-DHT added directly to Ta/Y marrow cultures caused an enhancement of CFU-E colony numbers compared with erythropoietin alone. 5 alpha-DHT inhibited colony formation at high concentrations. Testosterone had no effect on Tfm/Y erythroid colonies, whereas 5 beta-DHT and 5 alpha-DHT significantly inhibited colony formation. These results indicate that Tfm/Y erythroid bone marrow colonies may have an altered response to testosterone and its metabolites compared to that of Ta/Y erythroid colonies. We postulate that the pattern of androgen receptors in the erythroid progenitor cell compartment of Tfm/Y mice is different from that of Ta/Y mice.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D011944:Receptors, Androgen / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology*
D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D004921:Erythropoietin; D013739:Testosterone