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

Abstract

The mechanism by which oestrogen and hormone replacement therapy (HRT) maintain bone mass in women is still unclear. It has previously been shown that cells of osteoblast lineage in vivo, particularly osteocytes, express oestrogen receptor α (ERα). Nevertheless, it is still debatable whether oestrogen and the ovarian steroids have a direct affect on osteocytes. If they could regulate osteocyte ERα expression, this would be strong evidence for the involvement of these cells in the hormonal regulation of bone 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) for cellular localization of ERα protein or mRNA expression by indirect immunofluorescence, or by in situ hybridization combined with reverse transcriptase‐polymerase chain reaction (IS‐RT‐PCR) respectively. Image analysis showed that proportions of osteocytes positive for immunodetectable ERα 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 even when HRT was commenced 18 years after menopause. In contrast, grain volume/unit cell area of osteoblast mRNA signal was markedly higher when hormone‐deficient (0·055 ± 0·01) than when hormone‐replete (0·016 ± 0·004), with similar but non‐significant differences in osteocytes. This preliminary study indicates up‐regulation of osteocyte ERα protein by ovarian steroids in these patients, which is accompanied by decreased osteoblast ERα mRNA expression, providing further evidence for the involvement of osteocytes in the regulation of skeletal structure by ovarian steroids. Copyright © 1999 John Wiley & Sons, Ltd.

Effects of eccentric exercise training on cortical bone and muscle strength in the estrogen-deficient mouse

“…ciency (21,29). Given that the cortical bone response to mechanical loading is significantly attenuated in mice lacking ␣-estrogen receptor (28), it is reasonable to ask whether any benefits of resistance training might accrue in the absence of normal circulating estrogen.…”

Variation in estradiol level affects cortical bone growth in response to mechanical loading in sheep

“…Although more research is needed on the effects of E 2 on ER-␣ transcription, particularly in cortical bone, there is evidence that more estrogen leads to more estrogen receptors (Hoyland et al, 1999;Zhou et al, 2001;Zaman et al, 2006), with more receptors generally producing a greater osteogenic response to strain (Zaman et al, 2000;Lee et al, 2003). A reasonable prediction that follows from these results is that variation in E 2 and ER-␣ could alter cortical bone response to mechanical stimuli.…”

“…The relationship between ER-␣ number and strain sensitivity in osteoblasts is of particular interest because ER-␣ transcription depends in part on E 2 level. ER-␣ transcription is decreased by estrogen deficiency and increased by E 2 treatment in humans (Hoyland et al, 1999) and murine models (Lim et al, 1999;Zhou et al, 2001;Zaman et al, 2006).…”

Callus formation is related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing

“…By using the estrogen deficient OVX rat model with confirmed drop in serum estrogen, the impairment in healing outcomes was once again manifested by our data in the four-point bending tests of mechanical properties [31], callus morphometries [33,40], and also the expressions in genes related to callus formation [9] and ER-a and ER-b; and the possible relationships amongst them. ERs have been described to be modulated positively by the presence of estrogen [18,20]. ERs' function is also much related to activating bone formation in response to mechanical signals, especially by the ER-a [13,38,45].…”