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Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence.

ABSTRACT: Males and females show differences in the prevalence of many major diseases that have important inflammatory components to their etiology. These gender-specific diseases, which include autoimmune diseases, hepatocellular carcinoma, diabetes, and osteoporosis, are largely considered to reflect the actions of sex hormones on the susceptibility to inflammatory stimuli. However, inflammation reflects a balance between pro- and anti-inflammatory signals, and investigation of gender-specific responses to the latter has been neglected. Glucocorticoids are the primary physiological anti-inflammatory hormones in mammals, and synthetic derivatives of these hormones are prescribed as anti-inflammatory agents, irrespective of patient gender. We explored the possibility that sexually dimorphic actions of glucocorticoid regulation of gene expression may contribute to the dimorphic basis of inflammatory disease by evaluating the rat liver, a classic glucocorticoid-responsive organ. Surprisingly, glucocorticoid administration expanded the set of hepatic sexually dimorphic genes. Eight distinct patterns of glucocorticoid-regulated gene expression were identified, which included sex-specific genes. Our experiments also defined specific genes with altered expression in response to glucocorticoid treatment in both sexes, but in opposite directions. Pathway analysis identified sex-specific glucocorticoid-regulated gene expression in several canonical pathways involved in susceptibility to and progression of diseases with gender differences in prevalence. Moreover, a comparison of the number of genes involved in inflammatory disorders between sexes revealed 84 additional glucocorticoid-responsive genes in the male, suggesting that the anti-inflammatory actions of glucocorticoids are more effective in males. These gender-specific actions of glucocorticoids in liver were substantiated in vivo with a sepsis model of systemic inflammation.

SUBMITTER: Duma D

PROVIDER: S-EPMC4772900 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence.

Duma Danielle D Collins Jennifer B JB Chou Jeff W JW Cidlowski John A JA

Science signaling 20101012 143

Males and females show differences in the prevalence of many major diseases that have important inflammatory components to their etiology. These gender-specific diseases, which include autoimmune diseases, hepatocellular carcinoma, diabetes, and osteoporosis, are largely considered to reflect the actions of sex hormones on the susceptibility to inflammatory stimuli. However, inflammation reflects a balance between pro- and anti-inflammatory signals, and investigation of gender-specific responses ...[more]

PMID: 20940427

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Project description:Glucocorticoid hormones are a popular health indicator for animal populations. We find the relationship between health and glucocorticoids is inconsistent. However, variation in glucocorticoids is prevalent and may characterize populations in decline. We suggest monitoring the variation in glucocorticoids within populations might be more useful than mean glucocorticoid levels. Abstract Glucocorticoids are a popular tool for monitoring health of animal populations because they can increase with environmental stressors and can indicate chronic stress. However, individual responses to stressors create variation in the glucocorticoid–fitness relationship within populations. The inconsistency in this relationship calls into question the widespread use of glucocorticoids in conservation. We investigated the sources of variation in the glucocorticoid–fitness relationship by conducting a meta-analysis across a diverse set of species exposed to conservation-relevant stressors. We first quantified the extent to which studies inferred population health from glucocorticoids without first validating the glucocorticoid–fitness relationship in their own populations. We also tested whether population-level information like life history stage, sex and species longevity influenced the relationship between glucocorticoids and fitness. Finally, we tested for a universally consistent relationship between glucocorticoids and fitness across studies. We found more than half of peer-reviewed studies published between 2008 and 2022 inferred population health solely based on glucocorticoid levels. While life history stage explained some variation in the relationship between glucocorticoids and fitness, we found no consistent relationship between them. Much of the variation in the relationship could be the result of idiosyncratic characteristics of declining populations, such as unstable demographic structure, that coincided with large amounts of variation in glucocorticoid production. We suggest that conservation biologists capitalize on this variation in glucocorticoid production by declining populations by using the variance in glucocorticoid production as an early warning for declines in population health.

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Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence.

Publications

Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence.

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