Estrogen stimulates differentiation of megakaryocytes and modulates their expression of estrogen receptors α and β

Estrogen has multifunctional effects influencing growth, differentiation, and function in many tissues. High-dose estrogen has been shown to produce anabolic skeletal effects in the skeleton of postmenopausal women with increased megakaryocyte (MK) population in the bone marrow, suggesting a possible role for these cells in bone remodelling. To investigate if estrogen stimulates megakaryocytopoiesis and affects on estrogen receptor(ER) expression, CD34(+) cells were cultured for 6, 9, and 14 days plus or minus low-dose or high-dose 170 estradiol (E). Cells were immunolocalised for CD61, CD41, ERalpha and beta. ER mRNA expression was assessed by RT-PCR. Cells formed more CD61 positive MK colonies with low- and high-dose E treatment (P<0.001) at 6 and 9 days. CD41 expression was increased dose-dependently in MK (3- and 5-fold P<0.001) at 9 days. E-stimulated ERa expression at 6 days (P<0.001) whilst ERbeta was dose-dependently increased only at 9 days (P<0.01). ERalpha mRNA was increased at 6 days but not at 14 days whilst ERbeta mRNA expression was only increased at 14 days with E treatment. These results demonstrate that E stimulates the colony forming potential of CD34(+) cells to a more megakaryocytic phenotype in vitro. This finding together with the stimulation of ER protein and mRNA expression adds to the increasing evidence for a role for MKs in estrogen-induced bone formation. (C) 2004 Wiley-Liss, Inc.