Estrogen potentiates the combined effects of transforming growth factor-beta and tumor necrosis factor-alpha on adult human osteoblast-like cell prostaglandin E2 biosynthesis.

Reports that estrogen treatment modulates arachidonic acid metabolism by bone and bone cells are found in the literature. However, conflicting indications of the relationship that exists between estrogen and arachidonic acid metabolism emerge from the analysis of those reports. The present studies were undertaken to determine if estrogen effected the production of prostaglandins (PG) in human osteoblast-like (hOB) cell cultures derived from adults, under basal or cytokine-stimulated conditions. A 48-hour estrogen pretreatment did not modify hOB cell PG biosynthesis on a qualitative basis, and PGE2 formation predominated under all tested conditions. Estrogen pretreatment did lead to increased PGE2 production in specimens stimulated conjointly with transforming growth factor-beta1 and tumor necrosis factor-alpha ( p < 0.001). No changes in PGE2 production were observed in estrogen pretreated specimens stimulated singly with either tested cytokine, nor in samples in which either TGFbeta or TNF was replaced by interleukin-1beta. Anti-estrogen (ICI 164,384) inclusion prevented the estrogen-dependent increase in PGE2 production in the TGFbeta plus TNF-stimulated samples. These results suggest that an estrogen effect on bone cell prostaglandin biosynthesis may be most evident and significant under conditions in which the cells are exposed to multiple osteotropic cytokines, a condition that applies during the bone remodeling process.