7β-Hydroxy-epiandrosterone-mediated regulation of the prostaglandin synthesis pathway in human peripheral blood monocytes

7α-Hydroxy-DHEA, 7β-hydroxy-DHEA and 7β-hydroxy-EpiA are native metabolites of dehydroepiandrosterone (DHEA) and epiandrosterone (EpiA). Since numerous steroids are reported to interfere with inflammatory and immune processes, our objective was to test the effects of these hydroxysteroids on prostaglandin (PG) production and related enzyme gene expression. Human peripheral blood monocytes were cultured for 4 and 24 h in the presence of each of the steroids (1–100 nM), with and without addition of TNF-α (10 ng/mL). Levels of PGE2, PGD2 and 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) were measured in the incubation medium, and cell content of cyclooxygenase (COX-2), and PGE and PGD synthases (m-PGES1, H-PGDS, L-PGDS), and peroxisome proliferator activated receptor (PPAR-γ) was assessed by quantitative RT-PCR and Western blots. Addition of TNF-α resulted in elevated PG production and increased COX-2 and m-PGES1 levels. Among the three steroids tested, only 7β-hydroxy-EpiA decreased COX-2, m-PGES1 and PPAR-γ expression while markedly decreasing PGE2 and increasing 15d-PGJ2 production. These results suggest that 7β-hydroxy-EpiA is a native trigger of cellular protection through simultaneous activation of 15d-PGJ2 and depression of PGE2 synthesis, and that these effects may be mediated by activation of a putative receptor, specific for 7β-hydroxy-EpiA.