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.