title: Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae.
abstract: 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 PGE2 and levels of mRNA for inducible and constitutive prostaglandin G/H synthase (PGHS-2 and PGHS-1) and cytosolic phospholipase A2 in calvarial cultures. OVX MSups had twofold greater effects on PGHS-2 and medium PGE2 than other MSups. IL-1 receptor antagonist and anti-IL-1 alpha neutralizing antibody decreased MSup-stimulated PGHS-2 mRNA and PGE2 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 bone 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.
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington 06030, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: C C
authors.initials: CC
authors.lastname: Pilbeam
authors.forename: S J
authors.initials: SJ
authors.lastname: Vargas
authors.forename: E E
authors.initials: EE
authors.lastname: Morse
authors.forename: J A
authors.initials: JA
authors.lastname: Lorenzo
authors.forename: L G
authors.initials: LG
authors.lastname: Raisz
mesh_terms: D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010052:Ovariectomy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000096:biosynthesis*
chemical_list: D004967:Estrogens; D007375:Interleukin-1; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases