Transcriptomics,Genomics

Dataset Information

58

Sex-specific early growth hormone responses in mouse liver (Mus musculus)


ABSTRACT: Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies. Overall design: Liver RNA isolated from the following ten groups of mice was used in the present study: Sham surgery-treated and vehicle-injected male and female mice (M-Sham (n = 7) and F-Sham (n = 8), respectively); male and female mice hypophysectomized at adulthood (M-Hypox, n = 6; F-Hypox, n = 7); M-Hypox and F-Hypox mice treated with a single GH injection and killed 30 min later (M-Hypox + GH (30), n = 7; and F-Hypox + GH (30), n = 7); M-Hypox and F-Hypox mice treated with a single GH injection and killed 90 min later (M-Hypox + GH (90), n = 7; F-Hypox + GH (90), n = 7); M-Hypox and F-Hypox mice treated with two GH injections spaced 4 hr apart and killed 30 min after the second GH injection (M-Hypox + 2 GH, n = 8; and F-Hypox + 2 GH, n = 6). These RNA pools were used in eleven separate sets of competitive hybridization experiments in a loop design: 1) M-Sham vs. F-Sham; 2) M-Hypox vs. M-Sham; 3) M-Hypox + GH (30) vs. M-Hypox; 4) M-Hypox + GH (90) vs. M-Hypox; 5) M-Hypox + 2 GH vs. M-Hypox; 6) F-Hypox vs. F-Sham; 7) F-Hypox + GH (30) vs. F-Hypox; 8) F-Hypox + GH (90) vs. F-Hypox; 9) F-Hypox + 2 GH vs. M-Hypox; 10) M-Hypox vs. F-Hypox; and 11) M-Hypox + GH (30) vs. F-Hypox + GH (30). Fluorescent labeling of RNA and hybridization of the Alexa 555-labeled and Alexa 647-labeled aRNA samples to Agilent Whole Mouse Genome oligonucleotide microarrays (4 x 44K format; Agilent Technology, Palo Alto, CA; catalog # G4122F) were carried out, with dye swapping for each of the eleven hybridization experiments to eliminate dye bias. Two microarrays, one for each mixed cDNA sample, were hybridized for each of the eleven fluorescent reverse pairs, giving a total of 22 microarrays.

INSTRUMENT(S): Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version)

SUBMITTER: David J. Waxman  

PROVIDER: GSE17644 | GEO | 2010-01-27

SECONDARY ACCESSION(S): PRJNA118589

REPOSITORIES: GEO

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Publications

Intrinsic sex differences in the early growth hormone responsiveness of sex-specific genes in mouse liver.

Wauthier Valerie V   Sugathan Aarathi A   Meyer Rosana D RD   Dombkowski Alan A AA   Waxman David J DJ  

Molecular endocrinology (Baltimore, Md.) 20100211 3


Sex differences in liver gene expression are dictated by sex differences in circulating GH profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that could contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex differences characterize hepatic responses to plasma GH stimulation. Global RNA expression analysis identified two distinct cla  ...[more]

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