title: Sexual dimorphisms in zonal gene expression in mouse liver.
abstract: Many of the metabolic functions of the liver are localized either in the pericentral region (zone 3) or in the periportal region (zone 1). However, a systematic analysis of the heterogeneity and sexual dimorphism of gene expression in the liver is lacking. Our objective was to obtain sections of intact tissue from zone 1 and zone 3 from both male and female mouse liver, and to measure the patterns of gene expression in these sections. Zone 1 and zone 3 areas were isolated by laser capture microdissection of liver sections, total RNA was isolated and microarray analysis was conducted using Agilent Whole Mouse Genome oligo arrays. To investigate functional characteristics as well as upstream regulators of specific gene lists, we used Ingenuity Pathway Analysis. We identified more than 925 genes in zone 1 and more than 450 genes in zone 3 of both male and female mice. Sexual dimorphism in metabolic functions was present in zone 1 but not zone 3. In zone 1, canonical pathways related to gluconeogenesis were male predominant, while canonical pathways related to hepatic progenitor cells were female predominant. In addition, we also analyzed the upstream regulators of zone-specific genes. SREBF1 was male-specific in zone 1, while TRIM24 was female-specific in zone 3. These results demonstrate the heterogeneity and sexually dimorphic differences in gene expression in the liver.
authors.affiliation: Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Saito
authors.forename: Masahiko
authors.initials: M
authors.lastname: Negishi
authors.forename: E
authors.initials: E
authors.lastname: James Squires
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011786:Quality Control; D012727:Sex Characteristics; D014158:Transcription, Genetic
keywords: GH; HNF4; Hepatic zonation; LCM; Laser capture microdissection (LCM); RIN; RNA integrity number; STAT; Sexual dimorphism; growth hormone; hepatocyte nuclear factor 4 alpha; laser capture microdissection; signal transducer and activator of transcription