Some Molecular Mechanisms of Glucocorticoid Action

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Abstract
Glucocorticoids, in excess, profoundly affect the skeleton by increasing bone resorption, decreasing bone formation and altering intestinal absorption and renal excretion of mineral ions. The mechanisms underlying these actions are complex but many involve changes in expression of genes encoding critical proteins. Interaction of the glucocorticoid with its nuclear receptor results in the induction of either positive events (transactivation) by direct interaction with as-acting sequences, or negative (transrepression) events by repression of gene transcription and/or alteration of mRNA half-lives. An example is the inhibition by glucocorticoids of collagenase synthesis. Induction of the collagenase (procollagenase) gene by inflammatory mediators, such as interleukin-1, can be inhibited by glucocorticoid transrepression. The glucocorticoid-receptor complex binds to a protein complex AP-1; consisting of the proteins c-JUN and c-FOS) and prevents this complex from inducing activation of the procollagenase gene. These observations may be applicable to the interpretation of other glucocorticoid actions and explain some of their adverse effects on the skeleton.

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