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), PGF2 alpha, and 6-keto-PGF1 alpha, 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 X 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 microM), 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.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D013997:Time Factors
D011453:Prostaglandins; D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; D003994:Bucladesine; D003907:Dexamethasone; D015232:Dinoprostone