Age-related changes in human oestrogen receptor alpha 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-17beta 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 ERalpha 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 ERalpha per 10(6) cells. In contrast, strains derived from older women (n=20) had a mean value of 5.44+/-0.48 fmol of ERalpha per 10(6) cells. An age-related increase in ERalpha 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 ERalpha induction and indicate a loss of receptor regulation and diminution of ligand-receptor signal transduction with increasing donor age.
Division of Geriatrics and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
M A
MA
Ankrom
J A
JA
Patterson
P Y
PY
d'Avis
U K
UK
Vetter
M R
MR
Blackman
P D
PD
Sponseller
M
M
Tayback
P G
PG
Robey
J R
JR
Shapiro
N S
NS
Fedarko
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002675:Child, Preschool; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology*
D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol