Por que estrógeno e raloxifeno melhoram a densidade mineral óssea?: mecanismo de ação do estrógeno e de um modulador seletivo do receptor de estrógeno (SERM) no osso

• Autor(a) principal: Ramalho, Ana Claudia R. [UNIFESP]
• Data de Publicação: 2000
• Outros Autores: Lazaretti-Castro, Marise [UNIFESP], Cohen-Solal, Martine E. [UNIFESP], Vernejoul, Marie Christine de [UNIFESP]
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/001300000t6xz
• Texto Completo: http://dx.doi.org/10.1590/S0004-27302000000600005; http://repositorio.unifesp.br/handle/11600/1073
• topic: Estrogen; Cytokine; Osteoclast; SERM; Estrogen receptor; Apoptosis; Estrógeno; Citoquinas; Osteoclasto; SERM; Receptor de estrógeno; Apoptose

Estrogen deficiency is responsible for increased bone turnover in the postmenopausal period, and it can be prevented by estrogen replacement therapy. The way by which estrogen acts on bone cells is not fully understood and there are still many unsolved questions: (1) What is the target-cell of estrogen in bone? Estrogen receptor has been described in monocyte, osteoclast, bone marrow stromal cell and osteoblast, but it is still not clear what cell mediates the effect of estrogen in bone. (2) What are the mediators of estrogen action on bone? There is some controversy about the role of interleukin-6; most of the positive results were in animals, not in human; other cytokines are also involved, as tumoral necrosis factor and interleukin-1. (3) Is the anti-osteoclast effect of estrogen related to the apoptosis of osteoclast precursors? Some authors had already reported that estrogen increase apoptosis of osteoclasts precursors in animals, but it is not clear whether this effect is also present in humans. (4) What is the role of the bone marrow in osteoclastogenesis and in its inhibition by estrogen? Recently, it has been shown that stromal cells produce a membrane-associated factor (RANK-ligand) that stimulates osteoclast precursors, showing the importance of stromal cells in osteoclastogenesis and probably in the effect of estrogen in bone. (5) What is the transcription mechanism of estrogen action into the cell? NF-kappaB proteins may have an important role in post-menopausal osteoporosis, by regulating the secretion of cytokines involved on osteoclastogenesis. These questions on the mechanism of action of estrogens and also SERMs will be discussed in this review based on studies of literature and on recent studies of our group.