title: Estrogen stimulates differentiation of megakaryocytes and modulates their expression of estrogen receptors alpha and beta.
abstract: 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 17 beta estradiol (E). Cells were immunolocalised for CD61, CD41, ER alpha 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 ER alpha expression at 6 days (P < 0.001) whilst ER beta was dose-dependently increased only at 9 days (P < 0.01). ER alpha mRNA was increased at 6 days but not at 14 days whilst ER beta 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.
authors.affiliation: University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom. sb201@cam.ac.uk
authors.forename: Sharyn
authors.initials: S
authors.lastname: Bord
authors.forename: Emma
authors.initials: E
authors.lastname: Frith
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Ireland
authors.forename: Mike A
authors.initials: MA
authors.lastname: Scott
authors.forename: Jenny I O
authors.initials: JI
authors.lastname: Craig
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Compston
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005312:Fetal Blood; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger