Age-related changes in human oestrogen receptor α function and levels in osteoblasts

Oestrogen receptors (ERs) are present in human osteoblasts and mediate anti-resorptive effects on bone. Human osteoblast-like cells derived from different aged healthy female donors not on hormone replacement therapy were utilized under well-defined conditions in vitro to investigate ER function and levels, Treatment with 0.1 nM oestradiol-17 beta of cell strains derived from eight young women (less than 50 years of age) increased hydroxyproline levels significantly [an average (2.2 +/- 0.1 S.E.M.)-fold increase], whereas cells derived from nine older women (more than 50 years of age) were not significantly affected. Similarly, cell strains, derived from younger women, transfected with a consensus oestrogen-responsive element linked to chloramphenicol acetyltransferase exhibited a greater response to oestrogen than strains derived from older women, When basal ER alpha levels were measured by enzyme immunoassay and normalized on a per cell basis, osteoblast-like strains derived from younger women (n = 24) had a mean value of 2.54 +/- 0.16 fmol of ER alpha per 10(6) cells. In contrast, strains derived from older women (n = 20) had a mean value of 5.44 +/- 0.48 fmol of ER alpha per 10(6) cells. An age-related increase in ER alpha number was also observed in human skin-derived fibroblasts and directly in dermal biopsies from women not on hormone replacement therapy. The results demonstrate ligand concentration-dependent ER alpha induction and indicate a loss of receptor regulation and diminution of ligand-receptor signal transduction with increasing donor age.