Estrogens and hematopoiesis: characterization and studies on the mechanism of neutropenia.

The effect of ES upon hematopoiesis was studied following 4 to 24 weeks of administration in adult female mice. ES produced osteosclerosis, hepatomegaly, splenomegaly with an increase in splenic erythropoiesis mild anemai, and a relatively stable, moderately severe neutropenia. Intact and splenectomized mice failed to develop hepatic hematopoiesis to compensate for these blood changes. The neutropenia was characterized by a proportionally normal-sized marginal granulocyte pool and a reduced marrow granulocyte reserve in the marrow, cellularity, peroxidase-positive cells. CFU-S, and CFU-GM declined during 4 to 12 weeks of study in the same study period, splenic granulocytopoiesis increased as measured by these perameters, but it only partially compensated for the neutropenia. CSA was present in serum, and no inhibitors of in vitro granulocytopoiesis were detected. The direct addition of E3S to normal murine marrow cells in vitro failed to inhibit CFU=GM proliferation. Daily ES administration failed to inhibit in vivo granulocytopoiesis in diffusion chambers. These studies suggest that ES-induced neutropenia is not due to direct inhibition of CFU-S or CFU-GM proliferation or differentiation to mature granulocytes and by implication, suggest that it may be mediated through effects on the hematopoietic microenvironment.