Farris G M, Benjamin S A
Department of Pathology and Parasitology, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins 80523.
Am J Vet Res. 1993 Aug;54(8):1366-73.
Therapeutic doses of estrogens can cause fatal bone marrow damage in dogs, which are more sensitive than other species to these myelotoxic effects. Investigations with mice indicated that estrogens did not directly damage the bone marrow progenitor cells, but that the thymus responded to estrogen by producing a factor that inhibited bone marrow granulocyte-macrophage progenitor cell replication. A similar estrogen-induced myelopoiesis-inhibitory factor was produced by canine thymic cells in culture. This canine factor was more inhibitory to myelopoiesis than was the murine factor. Canine bone marrow progenitor cell growth was not significantly inhibited by direct estrogen treatment, which supported evidence for indirect thymus mediation of estrogen toxicity in vivo. Estrogen receptors were detected in canine nonlymphoid thymic cells by use of immunocytochemical staining. These findings indicate that the high estrogen sensitivity of dogs may relate to greater estrogen-induced myelopoiesis-inhibition by the thymus.
治疗剂量的雌激素可导致犬类出现致命的骨髓损伤，犬类比其他物种对这些骨髓毒性作用更为敏感。对小鼠的研究表明，雌激素不会直接损伤骨髓祖细胞，而是胸腺通过产生一种抑制骨髓粒细胞 - 巨噬细胞祖细胞复制的因子对雌激素作出反应。培养的犬胸腺细胞产生了一种类似的雌激素诱导的骨髓生成抑制因子。这种犬类因子对骨髓生成的抑制作用比鼠类因子更强。直接用雌激素处理并未显著抑制犬骨髓祖细胞的生长，这为雌激素在体内的毒性由胸腺间接介导提供了证据。通过免疫细胞化学染色在犬非淋巴细胞性胸腺细胞中检测到了雌激素受体。这些发现表明，犬类对雌激素的高敏感性可能与胸腺对雌激素诱导的骨髓生成抑制作用更强有关。
