Sex-dependent and growth hormone (GH)-dependent gene expression
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE1146 | GEO | 2004/03/27
SECONDARY ACCESSION(S): PRJNA87271
REPOSITORIES: GEO
Similar Datasets
Project description:Effect of continuous GH treatment on old rat liver. Male rats, 2-year-old, were treated with vehicle or human GH (0.34 microgram/gram body weight) for 3 weeks. Keywords: response of old rat liver to growth hormone
2005-07-19 | GSE2962 | GEO
Project description: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.
2010-01-27 | GSE17644 | GEO
Project description:A series of two color gene expression profiles obtained using Agilent 44K expression microarrays was used to examine sex-dependent and growth hormone-dependent differences in gene expression in rat liver. This series is comprised of pools of RNA prepared from untreated male and female rat liver, hypophysectomized (‘Hypox’) male and female rat liver, and from livers of Hypox male rats treated with either a single injection of growth hormone and then killed 30, 60, or 90 min later, or from livers of Hypox male rats treated with two growth hormone injections spaced 3 or 4 hr apart and killed 30 min after the second injection. The pools were paired to generate the following 6 direct microarray comparisons: 1) untreated male liver vs. untreated female liver; 2) Hypox male liver vs. untreated male liver; 3) Hypox female liver vs. untreated female liver; 4) Hypox male liver vs. Hypox female liver; 5) Hypox male liver + 1 growth hormone injection vs. Hypox male liver; and 6) Hypox male liver + 2 growth hormone injections vs. Hypox male liver. A comparison of untreated male liver and untreated female liver liver gene expression profiles showed that of the genes that showed significant expression differences in at least one of the 6 data sets, 25% were sex-specific. Moreover, sex specificity was lost for 88% of the male-specific genes and 94% of the female-specific genes following hypophysectomy. 25-31% of the sex-specific genes whose expression is altered by hypophysectomy responded to short-term growth hormone treatment in hypox male liver. 18-19% of the sex-specific genes whose expression decreased following hypophysectomy were up-regulated after either one or two growth hormone injections. Finally, growth hormone suppressed 24-36% of the sex-specific genes whose expression was up-regulated following hypophysectomy, indicating that growth hormone acts via both positive and negative regulatory mechanisms to establish and maintain the sex specificity of liver gene expression. For full details, see V. Wauthier and D.J. Waxman, Molecular Endocrinology (2008) This series is comprised of pools of liver RNA prepared from untreated male, hypophysectomized (‘Hypox’) male, untreated female and Hypox female rats (3-4 livers/pool), as well as liver RNA prepared from Hypox male rats treated with a single growth hormone injection and killed either 30, 60, or 90 minutes later (pool of n = 4 livers) or from Hypox male rats treated with two growth hormone injections spaced 3 or 4 hr apart (pool of n = 5 livers). The pools were paired to generate the following 6 direct microarray comparisons: 1) untreated male liver vs. untreated female liver; 2) Hypox male liver vs. untreated male liver; 3) Hypox female liver vs. untreated female liver; 4) Hypox male liver vs. Hypox female liver; 5) Hypox male liver + 1 growth hormone injection vs. Hypox male liver; and 6) Hypox male liver + 2 growth hormone injections vs. Hypox male liver. Dye swapping experiments were carried out for each of the six hybridization experiments, as follows. The Alexa 555-labeled cDNA from one of the two untreated male pools was mixed with the Alexa 647-labeled cDNA from one of the two untreated female pools. Similarly, Alexa 647-labeled cDNA from the second untreated male pool was mixed with the Alexa 555-labeled cDNA from the second untreated female pool. Together, these two mixed cDNA samples comprise a fluorescent reverse pair (dye swap). Dye swaps were similarly carried out for each of the five other competitive hybridization experiments, except that for experiments 5 and 6, a single pool of M-Hypox + GH liver cDNA, or a single pool of M-Hypox + 2GH liver cDNA, was used in each half of the fluorescent reverse pair. Two microarrays, one for each mixed cDNA sample, were hybridized for each of the six fluorescent reverse pairs, giving a total of 12 microarrays.
2008-05-24 | E-GEOD-11529 | biostudies-arrayexpress
Project description:Effect of continuous GH treatment on old rat liver. Male rats, 2-year-old, were treated with vehicle or human GH (0.34 microgram/gram body weight) for 3 weeks. Comparison of treated and untreated rats. Individual RNA were used for 4 microarray hybridization. Dye swapped.
2010-06-09 | E-GEOD-2962 | biostudies-arrayexpress
Project description:A reduction in hepatocyte growth hormone (GH)-signaling promotes non-alcoholic fatty liver disease (NAFLD). However, debate remains as to the relative contribution of the direct effects of GH on hepatocyte function vs indirect effects, via alterations in insulin-like growth factor 1 (IGF1). To isolate the role of hepatocyte GH receptor (GHR) signaling, independent of changes in IGF1, mice with adult-onset, hepatocyte-specific GHR knockdown (aHepGHRkd) were treated with a vector expressing rat IGF1 targeted specifically to hepatocytes. Compared to GHR-intact mice, aHepGHRkd reduced circulating IGF1 and elevated GH. In male aHepGHRkd, the shift in IGF1/GH did not alter plasma glucose or non-esterified fatty acids (NEFA), but was associated with increased insulin, enhanced systemic lipid oxidation and reduced white adipose tissue (WAT) mass. Livers of male aHepGHRkd exhibited steatosis associated with increased de novo lipogenesis, hepatocyte ballooning and inflammation. In female aHepGHRkd, hepatic GHR protein levels were not detectable, but moderate levels of IGF1 were maintained, with minimal alterations in systemic metabolism and no evidence of steatosis. Reconstitution of hepatocyte IGF1 in male aHepGHRkd lowered GH and normalized insulin, whole body lipid utilization and WAT mass. However, IGF1 reconstitution did not reduce steatosis or eliminate liver injury. RNAseq analysis showed IGF1 reconstitution did not impact aHepGHRkd-induced changes in liver gene expression, despite changes in systemic metabolism. These results demonstrate the impact of aHepGHRkd is sexually dimorphic and the steatosis and liver injury observed in male aHepGHRkd mice is autonomous of IGF1, suggesting GH acts directly on the adult hepatocyte to control NAFLD progression.
2020-07-11 | GSE154217 | GEO
Project description:This is the first use of cDNA microarrays to study the influence of GH transgenesis on liver gene expression in a non-mammalian vertebrate. Three groups of salmon were examined: transgenic on full ration (T), transgenic on restricted ration (R), and control nontransgenic (C). Daily weight gains in T were approximately 8-fold higher than in C, and 4-fold higher than in R. Differential gene expression in T, R, and C samples was determined using ~ 16,000 gene microarrays. In the GRASP microarray studies, only those features (cDNA spots on the microarrays) behaving similarly (e.g. greater than 2-fold up-regulated in T relative to C) in all slides of the study will be reported to minimize false positives occurring due to dye bias and technical variability. Coho salmon transcripts responding reproducibly to GH transgenesis with and without feed rationing will be reported. Many of the microarray-identified hepatic transcripts responsive to GH transgenesis with and without rationing are involved in iron homeostasis, metabolism, cellular proliferation, and innate immunity. Keywords: Impact of growth hormone transgenesis with and without ration restriction on global hepatic gene expression
2005-12-31 | GSE3477 | GEO
Project description:We investigated the effects of a single pulse of growth hormone on the transcriptional activation of STAT5 target genes in hypophysectomized male mouse liver. This GEO series is part of a larger study, where we investigated the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later. The STAT5-dependent but sex-independent early GH response genes Igf1 and Cish showed rapid, GH pulse-induced increases in chromatin accessibility and gene transcription, reversing the effects of hypophysectomy. Rapid increases in liver chromatin accessibility and transcriptional activity were also induced in hypophysectomized male mice for some (Ces2b, Ugt2b38) but not for other liver STAT5-dependent male-biased genes (Cyp7b1). Moreover, in pituitary-intact male mice, Igf1, Cish, Ces2b and Ugt2b38 all showed remarkable cycles of chromatin opening and closing, and associated cycles of induced gene transcription, which closely followed each endogenous pulse of liver STAT5 activity. Thus, the endogenous rhythms of male plasma GH pulsation dynamically open and then close liver chromatin at discrete, localized regulatory sites in temporal association with transcriptional activation of Igf1, Cish and a subset of STAT5-dependent male-biased genes.
2017-02-24 | GSE93379 | GEO
Project description:We investigated the effects of a single pulse of growth hormone on the transcriptional activation of STAT5 target genes in hypophysectomized male mouse liver. This GEO series is part of a larger study, where we investigated the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later. The STAT5-dependent but sex-independent early GH response genes Igf1 and Cish showed rapid, GH pulse-induced increases in chromatin accessibility and gene transcription, reversing the effects of hypophysectomy. Rapid increases in liver chromatin accessibility and transcriptional activity were also induced in hypophysectomized male mice for some (Ces2b, Ugt2b38) but not for other liver STAT5-dependent male-biased genes (Cyp7b1). Moreover, in pituitary-intact male mice, Igf1, Cish, Ces2b and Ugt2b38 all showed remarkable cycles of chromatin opening and closing, and associated cycles of induced gene transcription, which closely followed each endogenous pulse of liver STAT5 activity. Thus, the endogenous rhythms of male plasma GH pulsation dynamically open and then close liver chromatin at discrete, localized regulatory sites in temporal association with transcriptional activation of Igf1, Cish and a subset of STAT5-dependent male-biased genes.
2017-02-24 | GSE93381 | GEO
Project description:E2 and GH are critical regulators of growth and intermediate metabolism in mammals. Hypothyroidism causes endocrine and metabolic disturbances in the liver with features that mimic deficiencies of E2 or GH signalling. In this work, we used the hypothyroid-orchiectomized (TXOX) adult rat model to evaluate the influence of E2 and GH on the liver in terms of global changes in gene expression. This study shows the changes in hepatic transcriptome that were provoked by E2 benzoate (50 ug/kg; sc; 5 days per week x 27 days), intermittent GH administration (0.3 mg/kg/day;sc injection divided into two daily injections x 7 days) or the combination of E2 plus GH in TXOX rats. E2 influenced the liver transcriptome, particularly genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, gender, and immune responses. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. Notably, the combination of E2 and GH caused deleterious effects on transcriptional immune response. These results highlight the role of E2 as a critical regulator of liver metabolism in mammals and provide insights into the functional interplay between E2 and GH in the liver. Groups=4; Biological replicates = 4 per group; Samples=16; Reference samples=TXOX group. Adult (3 months old) male Sprague-Dawley rats (n=4 per group) were used throughout these experiments. The generation of TXOX was performed by adding methimazole (MMI; 0.05%) to the drinking water for 5 weeks starting on postnatal day (PND) 59 until sacrifice on PND94. Two weeks after starting MMI administration, male rats were castrated (OX) to make TXOX rats. Four days after OX, we began treatment with E2 benzoate (TXOXE2) or vehicle (TXOX) to TXOX rats for 20 days followed for 7 days by either vehicle plus GH (TXOXGH) or by E2 plus GH (TXOXE2GH). Twenty-four hours (in the case of E2) or twelve hours (in the case of GH) after the last injection, the animals were killed by exsanguinations. Portions of the liver were snap frozen in liquid nitrogen and stored at -80C until processed for mRNA analysis.
2014-02-28 | E-GEOD-50014 | biostudies-arrayexpress
Project description:Sequencing files provided here are mouse liver DNase-seq for male mouse livers collected at either a peak or trough of GH/STAT5 activity. This is part of a larger study that includes DNase-seq in mouse liver from hypophysectomized males, females, and hypox-male mice given a single dose of GH. DNase hypersensitivity site (DHS) analysis of these livers established that the naturally occurring, endogenous male rhythm of plasma GH pulse-stimulated liver STAT5 activation induces dynamic, repeated cycles of chromatin opening and closing at several thousand liver DHS and comprises a novel mechanism conferring male bias to liver chromatin accessibility.
2023-08-21 | GSE131848 | GEO