Effect of ovarian steroid deficiency on oestrogen receptor alpha expression in bone.
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 alpha (ERalpha). Nevertheless, it is still debatable whether oestrogen and the ovarian steroids have a direct affect on osteocytes. If they could regulate osteocyte ERalpha 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 ERalpha 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 ERalpha 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 ERalpha protein by ovarian steroids in these patients, which is accompanied by decreased osteoblast ERalpha mRNA expression, providing further evidence for the involvement of osteocytes in the regulation of skeletal structure by ovarian steroids.
Musculoskeletal Disease Research Group, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, U.K.
J A
JA
Hoyland
C
C
Baris
L
L
Wood
P
P
Baird
P L
PL
Selby
A J
AJ
Freemont
I P
IP
Braidman
D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D047628:Estrogen Receptor alpha; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047628:Estrogen Receptor alpha; D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen