OVARIECTOMY ENHANCES AND ESTROGEN REPLACEMENT INHIBITS THE ACTIVITY OF BONE-MARROW FACTORS THAT STIMULATE PROSTAGLANDIN PRODUCTION IN CULTURED MOUSE CALVARIAE

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 density had decreased significantly, 10-60% MSup increased medium PGE(2) and levels of mRNA for inducible and constitutive prostaglandin G/H synthase (PGHS-2 and PGHS-1) and cytosolic phospholipase A(2) in calvarial cultures. OVX MSups had twofold greater effects on PGHS-2 and medium PGE(2) than other MSups, IL-1 receptor antagonist and anti-IL-1 alpha 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 cells, 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 increases and estrogen decreases activity of these factors; and that IL-1 alpha activity, together with additional unknown factors, mediates the differential MSup effects.