ESTROGEN LOSS UP-REGULATES HEMATOPOIESIS IN THE MOUSE - A MEDIATING ROLE OF IL-6

We have previously demonstrated that ovariectomy causes an increase in the number of colony-forming unit granulocyte/macrophage (CFU-GM) and an upregulation of osteoclastogenesis in mice, both of which are medi ated by interleukin-6 (IL-6). IL-6 is involved in the development of s everal hematopoietic progenitors, including the burst-forming unit-ery throid (BFU-E) and multipotent CFUs (CFU-GEMM). Therefore, we performe d studies to examine if other hematopoietic progenitors, besides CFU-G M and their progeny, are affected by estrogen loss. We found that ovar iectomy caused an increase in the number of CFU-GEMM and BFU-E, as wel l as an increase of CFU-GM in marrow cells of the femur. Administratio n of 17 beta-estradiol or a neutralizing antibody against IL-6 prevent ed the ovariectomy-induced increase in the number of these progenitors in the marrow. Ovariectomy also caused an increase in the number of c irculating lymphocytes, neutrophils, and monocytes, which were suppres sed by administration of 17 beta-estradiol or the neutralizing antibod y against IL-6; however, the number of circulating platelets was unaff ected by loss of ovarian function. These data establish that, in addit ion to upregulation of osteoclastogenesis, loss of estrogens in the mo use causes widespread effects on hematopoiesis, which are apparently m ediated by IL-6.