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Wide-genome analysis of hepatocytes isolated from male and female rats treated with glucocorticoid.

ABSTRACT: Glucocorticoids are widely used therapeutically to suppress inflammatory/immune responses and most of their effects are produced either by altering transcription of specific genes directly, or by altering the expression of transcription factors that subsequently alter the expression of downstream genes. Relevant data from previous studies indicate that the number of genes regulated by glucocorticoid receptor exceeds 4000 in cells and that 358 different genes are regulated in the liver of adrenalectomized males rats treated with a chronic infusion of methylprednisolone for up to 1 week . However, differences in gene expression between males and females in response to glucocorticoid treatment in isolated hepatocytes are not known.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE24255 | GEO | 2010/10/31

SECONDARY ACCESSION(S): PRJNA132977

REPOSITORIES: GEO

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Project description:Males and females exhibit differences in the incidence of many major diseases including auto-immune diseases, hepatocellular carcinoma, diabetes, and osteoporosis, which all have important inflammatory components in their etiology. Glucocorticoids are the primary physiological anti-inflammatory hormone in all mammals and synthetic derivatives of these hormones are widely prescribed as anti-inflammatory agents irrespective of gender. Surprisingly we report a marked sexually dimorphic regulation of gene expression by glucocorticoids in the rat liver. Eight distinct patterns of glucocorticoid regulated genes were identified and two revealed genes that respond to glucocorticoid treatment in both sexes in opposite directions (anti-correlated genes. We also identified gender-specific groups of genes regulated by glucocorticoids. Pathways analysis identified sex-specific glucocorticoid regulated gene expression in several canonical pathways that have been implicated in human disease in which disease susceptibility is sex-biased. For example, comparison of number of genes involved in inflammatory disorders between sexes, revealed 84 additional glucocorticoid responsive genes in the male rat. Our data suggests that glucocorticoids thorough sexually-dimorphic regulation of gene expression modulate gender specific homeostatic functions in male and female liver. Adult males and females adrenalectomized Sprague-Dawley rats (8-10 weeks of age) (females Distrous 1) were treated with vehicle (Phosphate Buffered Saline – 400 µl) or Dexamethasone (1mg/Kg i.p.) purchased from Steraloids (Newport, RI). Liver was harvested 6 hours after treatment and kept in RNA later solution at 4oC over night. Samples were frozen and stored at -80oC. Three replicate microarrays were completed for each group (male vehicle, male dexamethasone, female vehicle and female dexamethasone) for a total of 12 microarrays. Each microarray was hybridized using a pooled RNA sample, and each pool was created from equal amounts of total RNA from three independent RNA samples, representing individual animals (n=9 animals per group). This approach provides appropriate biological replication within the constraints of a limiting number of microarrays (C. Kendziorski, R. A. Irizarry, K. S. Chen, J. D. Haag, M. N. Gould, Proc Natl Acad Sci U S A 102, 4252 Mar 22, 2005).

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Wide-genome analysis of hepatocytes isolated from male and female rats treated with glucocorticoid.

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