Estrogen blocks the cimetidine-induced suppression of CFU-GM.
Cimetidine, an H2-histamine antagonist used for the treatment of duodenal ulcers, has been shown to suppress granulocyte/macrophage colony forming cells (CFU-GM) in males. This study was initiated to examine the role of sex hormones on this cimetidine-induced suppression of CFU-GM. Preincubation of light-density, nonadherent bone marrow cells in male patients with 10(-6) M testosterone resulted in a modest decrease in the suppressive effect of cimetidine, whereas preincubation with 10(-6) M 17-beta-estradiol, for as little as 10 minutes, completely abolished the 50% reduction in colony numbers induced by cimetidine. Using supra-pharmacologic doses of cimetidine in order to detect CFU-GM suppression in female patients, identical results were obtained. Tamoxifen completely reversed this protective effect of estrogen and preincubation with hydroxyurea and the elimination of T cells from the system failed to alter any of these results, lending support to the likelihood that both cimetidine and estrogen directly affect marrow myeloid progenitor cells.
Worthington-White
D A
DA
Department of Pediatrics, University of Florida College of Medicine, Gainesville.
Gross
S
S
D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008297:Male; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
D013629:Tamoxifen; D013739:Testosterone; D004958:Estradiol; D002927:Cimetidine