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.
Animals Bone Marrow