ESTROGENS AND HEMATOPOIESIS - CHARACTERIZATION AND STUDIES ON THE MECHANISM OF NEUTROPENIA

  • 1 January 1980
    • journal article
    • research article
    • Vol. 95  (6) , 857-867
Abstract
The effect of ES [estrone] upon hematopoiesis was studied following 4-24 wk of administration in adult female mice. ES produced osteosclerosis, hepatomegaly, splenomegaly with an increase in splenic erythropoiesis, mild anemia 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 [cells capable of forming spleen colonies in irradiated mice], and CFU-GM [cells capable of forming granulocyte macrophages in culture] declined during 4-12 wk of study. Splenic granulocytopoiesis increased as measured by these parameters, but it only partially compensated for the neutropenia. Colony stimulating activity was present in serum, and no inhibitors of in vitro granulocytopoiesis were detected. The direct addition of estrone-3-sulfate 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. ES-induced neutropenia apparently is not due to direct inhibition of CFU-S or CFU-GM proliferation or differentiation to mature granulocytes; it may be mediated through effects on the hematopoietic microenvironment.