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Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

ABSTRACT: This study, using a growth hormone (GH)-deficient dwarf animal model and peripheral GH replacement, investigated the effects of circulating IGF-1 during adolescence on IGF-1 levels in the brain. Our results demonstrated that hippocampal IGF-1 protein concentrations during adolescence are highly regulated by circulating IGF-1, which were reduced by GH deficiency and restored by systematic GH replacement. In contrast, IGF-1 levels in the CSF were decreased by GH deficiency but not restored by GH replacement. Furthermore, analysis of gene expression using microarrays and RT-PCR indicated that circulating IGF-1 levels did not modify the transcription of IGF-1 or its receptor in the hippocampus but did regulate genes that are involved in microvascular structure and function, brain development, and synaptic plasticity, which potentially support brain structures involved in cognitive function during this important developmental period.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE29512 | GEO | 2011/07/21

SECONDARY ACCESSION(S): PRJNA141463

REPOSITORIES: GEO

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Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

Project description:This study, using a growth hormone (GH)-deficient dwarf animal model and peripheral GH replacement, investigated the effects of circulating IGF-1 during adolescence on IGF-1 levels in the brain. Our results demonstrated that hippocampal IGF-1 protein concentrations during adolescence are highly regulated by circulating IGF-1, which were reduced by GH deficiency and restored by systematic GH replacement. In contrast, IGF-1 levels in the CSF were decreased by GH deficiency but not restored by GH replacement. Furthermore, analysis of gene expression using microarrays and RT-PCR indicated that circulating IGF-1 levels did not modify the transcription of IGF-1 or its receptor in the hippocampus but did regulate genes that are involved in microvascular structure and function, brain development, and synaptic plasticity, which potentially support brain structures involved in cognitive function during this important developmental period. GH-deficient dwarf (dw/dw) and heterozygous (HZ) rats were identified at postnatal day 33-34. Starting from d35, dw/dw rats received subcutaneous injection of either 300µg GH (dw/dw+GH) or saline (dw/dw+sal) for 7d or 30d. HZ animals received saline for the same periods as controls. Animals (n=4/group for each time point) were sacrificed, the hippocampi were dissected, and total RNA were isolated for subsequent transcriptomic profiling.

2011-07-20 | E-GEOD-29512 | biostudies-arrayexpress

Rattus norvegicus

Project description:Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

| PRJNA141463 | ENA

Domestication and growth hormone transgenesis cause similar changes in gene expression profiles in coho salmon

Project description:By directly comparing gene expression in wild type, domestic, and GH transgenic strains of salmon, we have found that domestication and GH transgenesis are modifying similar genetic pathways. Genes in many different physiological pathways show modified expression in domestic and GH transgenic strains relative to wild-type, but effects are strongly correlated. Genes specifically involved in growth regulation (IGF-I, GHR, IGF-II, THR) are also concordantly regulated in domestic and transgenic fish, and both strains show elevated levels of circulating IGF-I. Muscle expression of GH in nontransgenic strains was found to be elevated in domesticated fish relative to wild type, providing a possible mechanism for growth enhancement. These data have implications for genetic improvement of existing domesticated species as well as regulation of emerging transgenic strains. Keywords: Expression profiling by array Microarray analyses were performed on four or five individual fish per group of wild type, domesticated, and GH transgenic salmon hybridized (one slide per individual) against a common wild-type RNA pool.

2009-03-08 | E-GEOD-13846 | biostudies-arrayexpress

Domestication and growth hormone transgenesis cause similar changes in gene expression profiles in coho salmon

2009-03-09 | GSE13846 | GEO

Transcriptional profiling by array of mouse hearts from animals with heterozygous truncation of Igf1 gene (HZ), or HZ treated with low doses of IGF-1 (substitutive therapy) against wild-type control

Project description:'This study investigates the effects produced by IGF-1 partial deficiency and if those effects were restored with the hormone''s substitutive therapy. Partial IGF-1 deficiency is achieved by heterozygous animals for a truncated gene of IGF-1 (Hz Igf1+/-), supplied by The Jackson Laboratories, which show a 60-75% reduction in circulating IGF-1 levels. The mice were a cross of 129SV Igf1+/- mice with non-consanguineous MF-1 mice to avoid consanguinity. Animals are treated for 10 days 2ug/100g bw/day with rhIGF-1 in succinate vehicle. After the 10 days of treatment, the animals were sacrificed, hearts were extracted, stored in RNAlater and frozen. On the day of the experiment, hearts were thawed, homogenised and subsequently processed as the RNA extraction kit instructions indicate (RNAqueousH-Micro Kit, Ambion, USA).'

2017-07-30 | E-MTAB-5791 | biostudies-arrayexpress

Transcription profiling by array of human adipose tissue from hypopituitary men before and after growth hormon (GH) treatment.

Project description:Adipose tissue is a major target of GH action. GH stimulates lipolysis and reduces fat mass. The molecular mechanism underlying cellular and metabolic effects of GH in adipose tissue is not well understood. The aim of this study is to identify GH-responsive genes that regulate lipid metabolism in adipose tissue. Eight men with GH deficiency underwent measurement of plasma free fatty acid (FFA), whole body lipid oxidation and fat biopsies before and after one month of GH treatment (0.5mg/day). Gene expression profiling was performed using Agilent 44K G4112F arrays utilising a two-colour design. Differentially expressed genes were identified using an empirical Bayes, moderate t-test, with a false discovery rate of < 5%. Genes involved in GH receptor signalling, lipolysis, triglyceride biosynthesis, adipocyte differentiation and function were analysed. Target genes were validated by quantitative RT-PCR. GH increased circulating IGF-I and FFA and stimulated fat oxidation. A total of 246 genes were differentially expressed, of which 135 were up-regulated and 111 down-regulated. GH enhanced adipose tissue expression of IGF-I and SOCS3. It did not change expression of key enzymes governing lipolysis, but differentially regulated genes promoting diacylglycerol syntheses. GH repressed hydroxysteroid (11-beta) dehydrogenase 1, which activates local cortisol production, and genes encoding components of extracellular matrix that regulate inflammation. GH induced concordant change in circulating IGF-I and expression in adipose tissue. GH stimulation of lipolysis is mediated at a translational and/or post-translational level. GH suppressed genes encoding local factors regulating adipocyte differentiation, function and inflammation.

2010-12-31 | E-MTAB-276 | biostudies-arrayexpress

Effects of social isolation stress on miRNA expression in the bed nucleus of stria terminalis (BNST) in male and female rats

Project description:Purpose: This study assessed putative sex differences in miRNA expression in the bed nucleus of the stria terminalis (BNST)—a sexually dimorphic brain region implicated in anxiety—of adult male and female rats that had been exposed throughout adolescence to social isolation (SI) stress. Methods: Male and female Sprague-Dawley rats underwent SI during adolescence or remained grouped housed (GH) till adulthood. Small RNA sequencing was performed on tissue extracted from the anterodorsal BNST. Results: SI compared to GH induced more anxiogenic-like effects in females compared to males and sex-dependent changes in miRNA expression in the BNST. Conclusions: The current study shows that housing conditions (either SI or GH) during adolescence regulates miRNA expression in a sex-specific manner in the sexually dimorphic area of the adBNST

2019-09-24 | GSE131289 | GEO

Experimental replacement therapy counters decreased IGF-1 levels in Huntington’s disease

Project description:Huntington’s disease (HD) is a monogenetic neurodegenerative disorder caused by the expansion of a polyglutamine (polyQ) stretch in huntingtin (htt). Here we show that mutant htt reduces the transcription of insulin-like growth factor 1 (IGF-1) and leads to loss of IGF-1 in HD brains, HD mouse models and mutant htt-transgenic microglial cells. IGF-1 replacement therapy by transplantation of genetically engineered mouse neuronal precursor cells (mNPCs) in a mouse model of HD reverted the motor phenotype and countered striatal neuronal loss.

2018-10-01 | GSE19291 | GEO

Frequent low-dose THC in adolescence disrupts microglia homeostasis and disables response to microbial infection

Project description:Adolescence is a time of experimentation with cannabis. We evaluated whether adolescent exposure to the drug's psychotropic consituent, delta-9-tetrahydrocannabidiol (THC), might persistently alter microglia function and brain immune responses to lipopolysaccaride administration.

2022-09-22 | GSE213734 | GEO

Transcription profiling of muscle from hypopituitary men before and after growth hormone treatment to investigate the effect of growth hormone on metabolic processes in muscle

Project description:Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic process in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and muscle biopsies before and after two weeks of GH treatment (0.5mg/day). Transcript profiles of four subjects were analysed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I), procollagens I and III were measured by RIA. GH increased serum IGF-I, procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in muscle by modulating circadian gene expression with possible metabolic consequences.

2008-01-31 | E-TABM-206 | biostudies-arrayexpress

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