Effect of ovarian steroid deficiency on oestrogen receptor alpha expression in bone

The mechanism by which oestrogen and hormone replacement therapy (HRT) main tain bone mass in women is still unclear. It has previously been shown that cells of osteoblast lineage in vivo, particularly osteocytes, express oest rogen receptor alpha (ER alpha). Nevertheless, it is still debatable whethe r oestrogen and the ovarian steroids hare a direct affect on osteocytes, If they could regulate osteocyte ER alpha expression, this would be strong ev idence for the involvement of these cells in the hormonal regulation of bon e mass. This study therefore aimed to compare bone biopsies from women who were replete with ovarian steroids (pre-ovariectomy or post-HRT) with those from the same women when hormone-deficient (post-ovariectomy or pre-HRT) f or cellular localization of ER alpha protein or mRNA expression bg indirect immunofluorescence, or by in situ hybridization combined with reverse tran scriptase-polymerase chain reaction (IS-RT-PCR) respectively, image analysi s showed that proportions of osteocytes positive for immunodetectable ER al pha were higher in hormone-replete than in hormone-deficient women (25 +/- SEM 3 per cent, 12 +/- SEM 4 per cent, respectively; n=5), with similar but non-statistically. significant changes in osteoblasts, This was observed e ven when HRT was commenced 18 years after menopause. In contrast, grain vol ume/unit cell area of osteoblast mRNA signal was markedly higher when hormo ne-deficient (0.055 +/- 0.01) than when hormone-replete (0.016 +/- 0.004), with similar but non-significant differences in osteocytes. This preliminar y study. indicates up-regulation of osteocyte ER alpha protein by ovarian s teroids in these patients, which is accompanied by decreased osteoblast ER alpha mRNA expression, providing further evidence for the involvement of os teocytes in the regulation of skeletal structure by ovarian steroids. (C) 1 999 John Wiley & Sons, Ltd.