Inhibition of prostaglandin biosynthesis in human adipose tissue by glucocorticosteroids

Cultured stromal cells derived from human sc adipose tissue synthesized and secreted into the medium prostaglandin E₂ (PGE₂), PGF_2α, and 6-keto-PGF_1α, a metabolite of prostacyclin. PGE₂ was quantitatively the major PG formed by these cells. Dexamethasone inhibited PG biosynthesis in a concentration- and time-dependent manner; dexamethasone (2.5 × 10⁻¹⁰ m) caused greater than 50% inhibition of PGE₂ synthesis after 24 h of incubation and 90% inhibition after 48 h. The effect of dexamethasone to inhibit PGE₂ synthesis was blocked by simultaneous incubation of cells with cortisol-21-mesylate, an antagonist of the binding of glucocorticosteroids to cytosolic receptors. (Bu)₂cAMP (1 mm), forskolin (10 μm), and 1-methyl-3-isobutylxanthine (0.1 mm) markedly stimulated PGE₂ biosynthesis in cultured adipose stromal cells. The inhibitory effect of dexamethasone on PGE₂ synthesis was attenuated by simultaneous incubation of cells with (Bu)₂cAMP. The results of this study suggest that glucocorticosteroids inhibit PG biosynthesis in adipose tissue stromal cells, whereas cAMP and certain analogs thereof stimulate PG biosynthesis and overcome the inhibitory action of glucocorticosteroids.