Effects of high-dose estrogen on murine hematopoietic bone marrow precede those on osteogenesis

High-dose estrogen both stimulates new medullary bone formation and suppres ses hematopoiesis in mouse long bones. To determine whether the latter resp onse is a direct consequence of the former, we compared the time course of estrogen's effects on osteogenesis and hematopoietic bone marrow. Flow cyto metry was employed to measure hematopoietic subpopulations in bone marrow f rom femurs of female mice killed at different times after commencing 0.5 mg estradiol/wk to each animal. Estrogen markedly reduced the number of leuco cytes (CD11a positive), which had already diminished by 75% after 4 days an d had virtually disappeared by 18 days. Specific populations showed a simil ar pattern of decline after estrogen, including B lymphocytes, monocytes, a nd endothelial cells. In contrast, the osteogenic precursor population show ed a marked increase after estrogen treatment, as assessed by assaying alka line phosphatase-positive colony-forming units (fibroblastic) ex vivo. Howe ver, this rise did not reach significance until 8 days after estrogen admin istration, suggesting that it follows rather than precedes estrogen's effec ts on hematopoiesis. We conclude that estrogen does not suppress hematopoie sis in mouse long bones as a direct consequence of its effects on osteogene sis.