Oestrogen action on bone cells.

Abstract

Sex steroids have an important impact on bone physiology. Oestrogen (E) appears to be the most important sex steroid in preventing osteoporosis in women. Despite the overwhelming evidence that oestrogens modulate bone growth and turnover in vivo, oestrogen receptors (ER) were detected only recently. Two forms of ER have been discovered so far, ERalpha and ERbeta. Both have been detected in osteoblasts and osteoclasts as well. A number of growth factors and cytokines appear to modulate bone resorption in vitro and in vivo. Among others, interleukin-1 and -6 and tumor necrosis factor alpha and beta were found to be extremely potent stimulators of bone resorption. Binding of different cytokines to their receptors in osteoblasts result in the release of soluble factors that act directly on osteoclasts to modulate their recruitment or activity. Thus, E, apart from the direct regulation of osteoclasts, which it achieves through its receptors, can inhibit the release of osteoclast stimulatory factors or enhance the release of osteoclast inhibitory factors. In general, E is an inhibitor of bone resorption that decreases both osteoclast numbers and activity. Recently, it has also been shown that it promotes apoptosis. Moreover, it also has anabolic effects on osteoblasts. However, E action on osteoclasts is superior in comparison with that on osteoblasts. Recent data have shown that transforming growth factor beta (TGFbeta) mediates the actions of E in bone. Following the example of raloxifene it may be proved that the role of TGFbeta in the actions of E in bone is central and has not only academic interest. More data are needed to elucidate this issue. Finally, recent data suggest the importance of E for bone maturation and development of peak bone mass in men. It seems likely that both E and androgens are required for the growth and maintenance of the adult male skeleton.