Selective cerebral overexpression of growth hormone alters cardiac function, morphology, energy metabolism and catcholamines in transgenic mice

Bohlooly‐Y, Mohammad; Bollano, Entela; Mobini, Reza; Soussi, B.; Törnell, Jan; Ömerovic, Elmir

doi:10.1016/j.ghir.2004.12.007

Cited by 13 publications

(19 citation statements)

References 42 publications

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“…The modest effects of bGH-Tg in our study is surprising considering that local overexpression of bGH in the CNS has previously been shown to modify cardiac function (Bohlooly-Y et al 2005a) and eating behaviour (Bohlooly-Y et al 2005b). Although changes in hypothalamic gene expression were observed, the authors also speculated that there was a change in sympathetic outflow, possibly in conjunction with an increase in serum corticosterone (Bohlooly-Y et al 2001) and serum leptin (Bohlooly-Y et al 2005b).…”

Section: Discussioncontrasting

confidence: 51%

“…Therefore, we believe that the central effects of bGH-Tg in terms of altered cardiac function and metabolism (Bohlooly-Y et al 2005a) are confined to brain regions other than the hippocampus and that the previously reported hippocampus-specific effects of systemic GH are weakly affected by local bGH-Tg.…”

Section: Discussionmentioning

confidence: 87%

“…This founder line exhibited the lowest level of bGH expression in the brain with the least systemic effect, compared with previous publications that have described a bGH-Tg strain from another founder line. The latter animals exhibited significant increases in body weight, serum bGH and serum IGF1 (Bohlooly-Y et al 2001(Bohlooly-Y et al , 2005a, probably due to leakage of bGH from the brain into the circulation. As we wanted to study the local expression of bGH in the brain, we used a founder line without significant effects on body weight or serum IGF1.…”

Section: Animalsmentioning

confidence: 95%

“…In mice, both the systemic transgenic (TG) overexpression of bovine GH (bGH) (Soderpalm et al 1999) and (albeit to a lesser degree) local brain overexpression of GH affect the brain and the body (Bohlooly-Y et al 2005b). Specifically, brain-specific bGH overexpression increases body weight and alters (mostly negatively) several cardiac measures of function (Bohlooly-Y et al 2005a), as well as increases eating behaviour (Bohlooly-Y et al 2005b). Two previous studies using TG models affecting GH signalling in the developing and adult brain have demonstrated an influence on the number of astrocytes in the cerebral cortex (Turnley et al 2002, Ransome et al 2004.…”

Section: Introductionmentioning

confidence: 99%

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Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

Walser¹,

Samà²,

Wickelgren³

et al. 2012

Journal of Endocrinology

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GH therapy improves hippocampal functions mainly via circulating IGF1. However, the roles of local GH and IGF1 expression are not well understood. We investigated whether transgenic (TG) overexpression in the adult brain of bovine GH (bGH) under the control of the glial fibrillary acidic protein (GFAP) promoter affected cellular proliferation and the expression of transcripts known to be induced by systemic GH in the hippocampus. Cellular proliferation was examined by 5-bromo-2 0 -deoxyuridine immunohistochemistry. Quantitative PCR and western blots were performed. Although robustly expressed, bGH-Tg did not increase either cell proliferation or survival. However, bGH-Tg modestly increased Igf1 and Gfap mRNAs, whereas other GH-associated transcripts were unaffected, i.e. the GH receptor (Ghr), IGF1 receptor (Igf1r), 2 0 ,3 0 -cyclic nucleotide 3 0 -phosphodiesterase (Cnp), ionotropic glutamate receptor 2a (Nr2a (Grin2a)), opioid receptor delta (Dor), synapse-associated protein 90/postsynaptic density-95-associated protein (Sapap2 (Dlgap2)), haemoglobin beta (Hbb) and glutamine synthetase (Gs (Glul )). However, IGF1R was correlated with the expression of Dor, Nr2a, Sapap2, Gs and Gfap. In summary, although local bGH expression was robust, it activated local IGF1 very modestly, which is probably the reason for the low response of previous GH-associated response parameters. This would, in turn, indicate that hippocampal GH is less important than endocrine GH. However, as most transcripts were correlated with the expression of IGF1R, there is still a possibility for endogenous circulating or local GH to act via IGF1R signalling. Possible reasons for the relative bio-inactivity of bGH include the bell-shaped dose-response curve and cell-specific expression of bGH.

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 87%

Section: Animalsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

Walser¹,

Samà²,

Wickelgren³

et al. 2012

Journal of Endocrinology

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“…During the last decade, the interest on GH overexpression effects has increased significantly, and several transgenic animal models overexpressing GH have been developed, including mammals (mouse and rat) and some teleost fishes (Oncorhynchus mykiss, Danio rerio) (Ikeda et al 1998, Devlin et al 2001, Lall et al 2004, Figueiredo et al 2007. However, there is few data on the GH overexpression effects in brain, a feature that has only been clearly analyzed using mouse GH transgenic models (Lall et al 2004, Bohlooly-Y et al 2005. As the GH secretion in the brain is regulated through a complex neuroendocrine control system that is modulated by hypothalamic peptides and neurotransmitter networks (Müller et al 1991), it would be interesting to determine which genes in this tissue could be associated with GH overexpression.…”

Section: Resultsmentioning

confidence: 99%

A comparative expression analysis of gene transcripts in brain tissue of non-transgenic and GH-transgenic zebrafish (Danio rerio) using a DDRT-PCR approach

Alves-Costa

Figueiredo

Lanes

et al. 2012

An. Acad. Bras. Ciênc.

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The presence of higher level of exogenous growth hormone (GH) in transgenic animals could lead to several physiological alterations. A GH transgenic zebrafish (Danio rerio) line was compared to nontransgenic (NT) samples of the species through a DDRT-PCR approach, with the goal of identifying candidate differentially expressed transcripts in brain tissues that could be involved in GH overexpression. Densitometric analyses of two selected amplification products, p300 and ADCY2, pointed to a significant lower gene expression in the transgenic zebrafish (104.02±57.71; 224.10±91.73) when compared to NT samples (249.75±30.08; 342.95±65.19). The present data indicate that p300 and ADCY2 are involved in a regulation system for GH when high circulating levels of this hormone are found in zebrafishes.

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Open‐chest ³¹P magnetic resonance spectroscopy of mouse heart at 4.7 Tesla

Lee

Nakamura

et al. 2006

Magnetic Resonance Imaging

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Purpose: To develop a rapid, robust, and accurate method for assessing myocardial energetics in mice and demonstrate its applicability to mouse models of acquired and genetic heart disease. Materials and Methods:We combined surface coil localization (10-mm diameter, tunable between 1 H and 31 P, using adiabatic half-passage radiofrequency pulses) and surgery (electrocautery removal of anterior chest wall) to create an open-chest method for acquiring in vivo 31 P nuclear magnetic resonance (NMR) cardiac spectra from mice at 4.7T within 12 minutes. Normal BALB/c mice, BALB/c with myocardial infarction (MI), cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta knockout (KO) (CR-PPARd -/-) and control loxP-flanked Ppard (Ppardflox/flox ) mice were examined. Results:The mean phosphocreatine (PCr)/adenosine triphosphate (ATP) ratios in control BALB/c mice, BALB/c MI mice, Ppard flox/flox mice, and PPAR-␦ KO mice were 2.13 Ϯ 0.09 (N ϭ 11), 1.35 Ϯ 0.07 (N ϭ 9, P Ͻ 0.001 vs. BALB/c control), 1.92 Ϯ 0.09 (N ϭ 5), and 1.31 Ϯ 0.12 (N ϭ 5, P Ͻ 0.005 vs. Ppard flox/flox control), respectively. The significant depression of myocardial PCr/ATP we observed in these genetic/acquired models of heart disease was in accord with previous data from analogous large animal models. No NMR signal contamination from chamber blood or adjacent skeletal muscle was identified. Conclusion: This new technique provides cardiac31 P spectra suitable for accurate quantitative analysis in a relatively short acquisition time, is suitable for terminal studies of mouse myocardial energy metabolism, and could be installed in virtually any NMR laboratory to study myocardial energetics in numerous mouse models of human heart disease.

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Selective cerebral overexpression of growth hormone alters cardiac function, morphology, energy metabolism and catcholamines in transgenic mice

Cited by 13 publications

References 42 publications

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

A comparative expression analysis of gene transcripts in brain tissue of non-transgenic and GH-transgenic zebrafish (Danio rerio) using a DDRT-PCR approach

Open‐chest ³¹P magnetic resonance spectroscopy of mouse heart at 4.7 Tesla

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Selective cerebral overexpression of growth hormone alters cardiac function, morphology, energy metabolism and catcholamines in transgenic mice

Cited by 13 publications

References 42 publications

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

A comparative expression analysis of gene transcripts in brain tissue of non-transgenic and GH-transgenic zebrafish (Danio rerio) using a DDRT-PCR approach

Open‐chest 31P magnetic resonance spectroscopy of mouse heart at 4.7 Tesla

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Open‐chest ³¹P magnetic resonance spectroscopy of mouse heart at 4.7 Tesla