Glucocorticoid action: A mechanism involving nuclear and non-nuclear pathways

The potent anti-inflammatory actions of the corticosteroid hormones have been appreciated by dermatologists since the introduction of synthetic glucocorticoid in 1950. Despite the explosion of knowledge regarding basic cell and molecular biology during the ensuing 30 years, a complete mechanistic picture of how glucocorticoids exert their diverse action on the complex cellular physiology of the skin is lacking. On first consideration, it is not surprising that corticosteroids can inhibit inflammatory responses because inflammation itself is an accelerated metabolic process and glucocorticoids are generally inhibitory on skin cell metabolism. However, a large body of evidence is now accumulating to suggest that glucocorticoids may be much more specific in the manoeuvre through which they exert their anti-inflammatory actions. This idea derives both from the finding of specific receptors for glucocorticoids in cell types derived from skin and the observation of specific responses mediated by defined gene products. However, the induction or inhibition of specific genes cannot explain all of the observed responses of skin elements to glucocorticoid treatment. The following review has, therefore, been organized with respect to a possible mechanism whereby the glucocorticoid receptor can influence both genomic and non-genomic events. Central to this discussion will be the corticosteroid inhibition of prostaglandin production. Data will also be drawn from the glucocorticoid regulation of the pituitary hormones, growth hormone and ACTH.