Research ArticlePhysiology

Sexually Dimorphic Actions of Glucocorticoids Provide a Link to Inflammatory Diseases with Gender Differences in Prevalence

Science Signaling  12 Oct 2010:
Vol. 3, Issue 143, pp. ra74
DOI: 10.1126/scisignal.2001077

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Gender Bias for Glucocorticoids

The release of glucocorticoids from adrenal glands during times of stress activates transcription of genes encoding factors that suppress inflammation. Synthetic glucocorticoids, such as dexamethasone, are widely prescribed for inflammatory conditions. Because several diseases with inflammatory components show gender-specific differences in prevalence, Duma et al. investigated whether glucocorticoid responses were also gender-biased. Microarray analysis of messenger RNA abundance indicated that dexamethasone treatment of male and female rats increased the number of genes with gender-specific differences in liver expression. In male rat liver, more genes implicated in inflammatory disorders showed dexamethasone-induced alterations (usually decreases) in expression than did genes in female rat liver. In rats injected with lipopolysaccharide (LPS) to trigger systemic inflammation and subsequently treated with dexamethasone, more males than females survived. Male rats produced lower concentrations of inflammatory factors in response to dexamethasone treatment, and ovariectomy improved the survival of female rats after LPS challenge and dexamethasone treatment. The accompanying Perspective by Chrousos discusses the evolutionary context for gender-specific differences in responses to stress, inflammation, and glucocorticoids.