Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis

THE finding that aspirin-like drugs act by inhibiting prostaglandin (PG) synthetase was reported by Vane et al.¹, and the possible effects of anti-inflammatory steroids on PG production have since been a matter of controversy. Although some studies have indicated no appreciable effect of the corticosteroids on PG synthetase^1-4, other investigators have presented evidence that corticosteroids may act by inhibiting the biosynthesis or release of PGs. The latter data were derived from studies on a variety of tissues such as skin⁵, adipose tissue⁴, inflamed synovia^6,7, cultured fibroblasts⁸ and fibrosarcoma cells⁹. No satisfactory explanation for these controversial results has been offered, nor has the mechanism of this possible effect of corticosteroids on PG production been properly elucidated. The mechanism of action of the steroid hormones on their target organs has been clarified in recent years. These hormones are now thought to act primarily by stimulating transcription, thus controlling the rate of synthesis of certain key proteins (see ref. 10 for review). Many of the actions of the colt;rticosteroids on intermediary metabolism are indeed known to involve the induction of synthesis of specific enzyme proteins. We report here that corticosteroids influence PG production by a mechanism involving RNA and protein synthesis.