Estrogen (E) deficiency is the major cause of postmenopausal osteoporosis. Understanding the mechanisms by which E regulates bone metabolism is critical for developing novel approaches to prevent and treat this disorder. We will focus on defining mechanisms for the age-related decrease in bone formation and the role of E deficiency in mediating this decrease. We will use novel methods we have developed to examine gene expression in highly purified bone marrow osteoblastic cells. We will test whether the increase in bone formation previously observed following acute E treatment in women is associated with an increase in markers of Wnt/bone morphogenetic protein (BMP) signaling and/or production and in othe genes related to bone formation by osteoblastic cells.