Worthington-White D A, Gross S
Department of Pediatrics, University of Florida College of Medicine, Gainesville.
Exp Hematol. 1993 Jan;21(1):16-20.
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.
西咪替丁是一种用于治疗十二指肠溃疡的H2组胺拮抗剂,已被证明可抑制男性的粒细胞/巨噬细胞集落形成细胞(CFU-GM)。开展这项研究是为了考察性激素在西咪替丁诱导的CFU-GM抑制中的作用。男性患者的低密度非贴壁骨髓细胞与10(-6)M睾酮预孵育后,西咪替丁的抑制作用略有下降,而与10(-6)M 17-β-雌二醇预孵育,哪怕仅10分钟,也能完全消除西咪替丁诱导的集落数减少50%的效应。为检测女性患者的CFU-GM抑制情况而使用超药理剂量的西咪替丁时,得到了相同的结果。他莫昔芬完全逆转了雌激素的这种保护作用,用羟基脲预孵育以及从系统中去除T细胞均未能改变任何这些结果,这支持了西咪替丁和雌激素均直接影响骨髓髓系祖细胞的可能性。