Male age-related bone loss is caused, at least in part, by hypogonadism that occurs with advancing age. The study of the effects of sex steroids on bone physiology in men has recently highlighted the central role of estrogens on bone pathophysiology. This review focuses on particular aspects of bone physiology and pathophysiology in aging men, noting both the similarities to and the differences from female counterparts. In particular, the role of sex steroids on bone sexual dimorphism in health and disease has been analyzed.

We know that the Yin Yang 1 protein (YY1) overexpression is positively and strongly correlated with the degree of malignancy of bone tumors. Therefore, we questioned whether we could influence cell invasiveness by deleting YY1 in human osteosarcoma cells (SaOs-2), as tested in Matrigel-coated filters and metastasis implantation of such osteosarcoma cells in vivo, by serial analysis with nuclear magnetic resonance. Moreover, we focused our work on the chemokine receptor CXCR4 and its inhibition by T22 antibody, as well as on systemic (direct in vivo assay) and computer-assisted imaging of angiogenesis-related metastasis. Results showed that cell invasiveness and metastasis implantation by wild-type SaOs-2 cells, as evaluated by histology and immunohistochemistry, are associated with up-regulation of CXCR4 expression, which in turn was significantly reduced by T22. In addition, deletion of YY1 (siRNAYY1-SaOs-2) induced a significant decrease of cell invasion and metastasis growth. This phenomenon was associated with decreased vascular endothelial growth factor (VEGF)/angiogenesis and a complex rearrangement of the gene expression profile as evaluated by microarray analysis. In conclusion, YY1 and VEGF/CXCR4 seem to intervene in the pathogenesis of the malignant phenotype of osteosarcoma by acting on cell invasiveness and metastasis growth. [Cancer Res 2008;68(6):1797-808]

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The study of the sexual behaviour in this man with aromatase deficiency suggests that oestrogens in humans do not affect gender-identity and sexual orientation but could have a role in male sexual activity.