Estradiol enhances insulin-like growth factor I mRNA and has anabolic effects in osteoblastic cells from rat calvariae and long bones

Although the beneficial effects of estrogen in the treatment of postmenopausal osteoporosis are well documented, only recent improvements in bone cell culture models (better defined osteoblastic cell populations, omission of Phenol Red from culture media) enabled several investigators to show small, but reproducible, direct effects of estradiol on various osteoblastic cell types in vivo. Such findings were supported by the identification of low numbers of high-affinity estrogen binding sites in bone cells derived from different mammalian species. The likely physiological relevance of the in vitro results is indicated by the specificity for 17β-E2 and the requirement for nanomolar concentrations of the hormone, consistent with a Kd of 0.6 nM for estradiol binding to its receptor. In bone cells in vitro, estradiol decreases PTH-stimulation of adenylate cyclase which may reduce bone resorption, and has anabolic effects by stimulating matrix synthesis and cell proliferation. The latter effects were abolished in the presence of IGF-I antibodies, and since estradiol may directly regulate IGF-I gene expression, IGF-I appears to be a estrogen-mediator for anabolic effects and may, when associated with BPs, act in an autocrine/paracrine fashion in bone.