Premium
Endogenous hepatic glucocorticoid receptor signaling coordinates sex‐biased inflammatory gene expression
Author(s) -
Quinn Matthew A.,
Cidlowski John A.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-278309
Subject(s) - sexual dimorphism , glucocorticoid receptor , biology , gene , gene expression , endocrinology , proinflammatory cytokine , medicine , glucocorticoid , receptor , inflammation , gene expression profiling , regulation of gene expression , immunology , genetics
An individual's sex affects gene expression and many inflammatory diseases present in a sex‐biased manner. Glucocorticoid receptors (GRs) are regulators of inflammatory genes, but their role in sex‐specific responses is unclear. Our goal was to evaluate whether GR differentially regulates inflammatory gene expression in male and female mouse liver. Twenty‐five percent of the 251 genes assayed by nanostring analysis were influenced by sex. Of these baseline sexually dimorphic inflammatory genes, 82% was expressed higher in female liver. Pathway analyses defined pattern‐recognition receptors as the most sexually dimorphic pathway. We next exposed male and female mice to the proinflammatory stimulus LPS. Female mice had 177 genes regulated by treatment with LPS, whereas males had 149, with only 66% of LPS‐regulated genes common between the sexes. To determine the contribution of GR to sexually dimorphic inflammatory genes we performed nanostring analysis on liver‐specific GR knockout (LGRKO) mice in the presence or absence of LPS. Comparing LGRKO to GR flox/flox revealed that 36 genes required GR for sexually dimorphic expression, whereas 24 genes became sexually dimorphic in LGRKO. Fifteen percent of LPS‐regulated genes in GR flox/flox were not regulated in male and female LGRKO mice treated with LPS. Thus, GR action is influenced by sex to regulate inflammatory gene expression.—Quinn, M. A., Cidlowski, J. A. Endogenous hepatic glucocorticoid receptor signaling coordinates sex‐biased inflammatory gene expression. FASEB J. 30, 971–982 (2016). www.fasebj.org