OVARIECTOMY ENHANCES AND ESTROGEN REPLACEMENT INHIBITS THE ACTIVITY OF BONE-MARROW FACTORS THAT STIMULATE PROSTAGLANDIN PRODUCTION IN CULTURED MOUSE CALVARIAE
H. Kawaguchi et al., OVARIECTOMY ENHANCES AND ESTROGEN REPLACEMENT INHIBITS THE ACTIVITY OF BONE-MARROW FACTORS THAT STIMULATE PROSTAGLANDIN PRODUCTION IN CULTURED MOUSE CALVARIAE, The Journal of clinical investigation, 96(1), 1995, pp. 539-548
To examine PG production in estrogen deficiency, we studied effects on
cultured neonatal mouse calvariae of bone marrow supernatants (MSup)
from sham-operated (SHAM), ovariectomized (OVX), or 17 beta-estradiol
(OVX+E)-treated mice, MSups were obtained 3 wk after OVX when bone den
sity had decreased significantly, 10-60% MSup increased medium PGE(2)
and levels of mRNA for inducible and constitutive prostaglandin G/H sy
nthase (PGHS-2 and PGHS-1) and cytosolic phospholipase A(2) in calvari
al cultures. OVX MSups had twofold greater effects on PGHS-2 and mediu
m PGE(2) than other MSups, IL-1 receptor antagonist and anti-IL-1 alph
a neutralizing antibody decreased MSup-stimulated PGHS-2 mRNA and PGE(
2) levels and diminished differences among OVX, sham-operated, and OVX
+E groups, In contrast, antibodies to IL-1 beta, IL-6, IL-11, and TNF
alpha had little effect. There were no significant differences in IL-1
alpha concentrations or IL-1 alpha mRNA levels in MSups or marrow cel
ls, PGHS-2 mRNA in freshly isolated tibiae from OVX mice was slightly
greater than from sham-operated. We conclude that bane marrow factors
can increase PG production through stimulation of PGHS-2; that OVX inc
reases and estrogen decreases activity of these factors; and that IL-1
alpha activity, together with additional unknown factors, mediates th
e differential MSup effects.