scholarly journals The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2664
Author(s):  
Sarmed Al-Samerria ◽  
Sally Radovick
Keyword(s):  
Mouse Models ◽  
Genetically Modified ◽  
Somatic Growth ◽  
Feedback Regulation ◽  
Somatic Development ◽  
Carbohydrate And Lipid Metabolism ◽  
Single Exception ◽  
Regulatory Effects ◽  
Regulation Of Growth

In mammals, the neuroendocrine system, which includes the communication between the hypothalamus and the pituitary, plays a major role in controlling body growth and cellular metabolism. GH produced from the pituitary somatotroph is considered the master regulator of somatic development and involved, directly and indirectly, in carbohydrate and lipid metabolism via complex, yet well-defined, signaling pathways. GH production from the pituitary gland is primarily regulated by the counter-regulatory effects of the hypothalamic GHRH and SST hormones. The role of IGF-1 feedback regulation in GH production has been demonstrated by pharmacologic interventions and in genetically modified mouse models. In the present review, we discuss the role of IGF-1 in the regulation of the GH-axis as it controls somatic growth and metabolic homeostasis. We present genetically modified mouse models that maintain the integrity of the GH/GHRH-axis with the single exception of IGF-1 receptor (IGF-1R) deficiency in the hypothalamic GHRH neurons and somatotroph that reveals a novel mechanism controlling adipose tissues physiology and energy expenditure.

scholarly journals Melatonin restores Muc2 depletion induced by V. vulnificus VvpM via melatonin receptor 2 coupling with Gαq

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Young-Min Lee ◽  
Jong Pil Park ◽  
Young Hyun Jung ◽  
Hyun Jik Lee ◽  
Jun Sung Kim ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Mouse Models ◽  
Functional Role ◽  
Bacterial Toxin ◽  
Intestinal Epithelial ◽  
Melatonin Receptor ◽  
Intestinal Mucin ◽  
Infection Treatment ◽  
Regulatory Effects

Abstract Background Melatonin (5-methoxy-N-acetyltryptamine), a hormone produced in the pineal gland, has a variety of biological functions as an antioxidant, but a functional role of melatonin in the regulation of intestinal mucin (Muc) production during bacterial infection has yet to be described in detail. In this study, we investigate the effects of melatonin during Muc2 repression elicited by the Gram-negative bacterium V. vulnificus. Methods Mucus-secreting human HT29-MTX cells were used to study the functional role of melatonin during Muc2 depletion induced by the recombinant protein (r) VvpM produced by V. vulnificus. The regulatory effects of melatonin coupling with melatonin receptor 2 (MT2) on the production of reactive oxygen species (ROS), the activation of PKCδ and ERK, and the hypermethylation of the Muc2 promoter as induced by rVvpM were examined. Experimental mouse models of V. vulnificus infection were used to study the role of melatonin and how it neutralizes the bacterial toxin activity related to Muc2 repression. Results Recombinant protein (r) VvpM significantly reduced the level of Muc2 in HT29-MTX cells. The repression of Muc2 induced by rVvpM was significantly restored upon a treatment with melatonin (1 μM), which had been inhibited by the knockdown of MT2 coupling with Gαq and the NADPH oxidase subunit p47 phox. Melatonin inhibited the ROS-mediated phosphorylation of PKCδ and ERK responsible for region-specific hypermethylation in the Muc2 promoter in rVvpM-treated HT29-MTX cells. In the mouse models of V. vulnificus infection, treatment with melatonin maintained the level of Muc2 expression in the intestine. In addition, the mutation of the VvpM gene from V. vulnificus exhibited an effect similar to that of melatonin. Conclusions These results demonstrate that melatonin acting on MT2 inhibits the hypermethylation of the Muc2 promoter to restore the level of Muc2 production in intestinal epithelial cells infected with V. vulnificus.

scholarly journals The role of galanin and its receptor in the feedback regulation of growth hormone secretion.

Endocrinology ◽  
1996 ◽  
Vol 137 (12) ◽  
pp. 5303-5310 ◽  
Author(s):  
Y Y Chan ◽  
E Grafstein-Dunn ◽  
H A Delemarre-van de Waal ◽  
K A Burton ◽  
D K Clifton ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Feedback Regulation ◽  
Regulation Of Growth

Hemoglobin adducts of furfuryl alcohol in genetically modified mouse models: Role of endogenous sulfotransferases 1a1 and 1d1 and transgenic human sulfotransferases 1A1/1A2

2018 ◽  
Vol 295 ◽  
pp. 173-178 ◽  
Author(s):  
Bernhard H. Monien ◽  
Benjamin Sachse ◽  
Walter Meinl ◽  
Klaus Abraham ◽  
Alfonso Lampen ◽  
...  
Keyword(s):  
Mouse Models ◽  
Furfuryl Alcohol ◽  
Genetically Modified ◽  
Hemoglobin Adducts

scholarly journals Genetically modified animal models and Osteoimmunology

2017 ◽  
Vol 61 (3) ◽  
pp. 236
Author(s):  
E. DOUNI (Ε.ΝΤΟΥΝΗ)
Keyword(s):  
Mouse Models ◽  
Dna Sequences ◽  
Mouse Genome ◽  
Genetically Modified ◽  
Therapeutic Approaches ◽  
Pathogenic Mechanisms ◽  
Technological Advances ◽  
Continuous Interaction ◽  
Almost All

The completion of the human and mouse genome DNA sequences easily enabled chromosomal localization for each gene, whereas the role of each gene remains largely unknown. Functional Genomics constitutes the new area of Molecular Biology that aims to identify the function(s) of each gene in order to understand the pathogenic mechanisms in various human diseases. The mouse has been extensively used more than any other animal organism in biomedical research, because, except for the similarities it displays with humans, its genome can be genetically modified rather easily. During the last two decades, technological advances enable almost all kinds of mutations in the mouse genome. More specifically, the study of genetically modified mice revealed the continuous interaction between various systems within the organism, such as the interplay between the skeletal and the immune system, introducing the interdisciplinary area of Osteoimmunology. The cytokine RANKL constitutes the key molecule in Osteoimmunology, by regulating osteoclastogenesis, while deregulation of RANKL expression leads to diseases such as osteopetrosis or osteoporosis. In our laboratory we have recently generated, using state-of-the-art technologies, unique mouse models of RANKL-induced osteopetrosis or osteoporosis. These mouse models constitute excellent systems for the study of underlying pathogenic mechanisms and for the evaluation of novel therapeutic approaches at the preclinical level.

scholarly journals Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice

2005 ◽  
Vol 43 (5) ◽  
Author(s):  
Kristiaan Wouters ◽  
Ronit Shiri-Sverdlov ◽  
Patrick J. van Gorp ◽  
Marc van Bilsen ◽  
Marten H. Hofker
Keyword(s):  
Mouse Models ◽  
Molecular Mechanisms ◽  
Genetically Modified ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Density Lipoprotein Receptor ◽  
Mutant Forms ◽  
Deficient Mice

AbstractHyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the

scholarly journals The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models

2011 ◽  
Vol 212 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Taija Saloniemi ◽  
Heli Jokela ◽  
Leena Strauss ◽  
Pirjo Pakarinen ◽  
Matti Poutanen
Keyword(s):  
Mouse Models ◽  
Drug Targets ◽  
Genetically Modified ◽  
Cholesterol Biosynthesis ◽  
Sex Steroid ◽  
Target Cells ◽  
Metabolic Role

Disturbed action of sex steroid hormones, i.e. androgens and estrogens, is involved in the pathogenesis of various severe diseases in humans. Interestingly, recent studies have provided data further supporting the hypothesis that the circulating hormone concentrations do not explain all physiological and pathological processes observed in hormone-dependent tissues, while the intratissue sex steroid concentrations are determined by the expression of steroid metabolising enzymes in the neighbouring cells (paracrine action) and/or by target cells themselves (intracrine action). This local sex steroid production is also a valuable treatment option for developing novel therapies against hormonal diseases. Hydroxysteroid (17β) dehydrogenases (HSD17Bs) compose a family of 14 enzymes that catalyse the conversion between the low-active 17-keto steroids and the highly active 17β-hydroxy steroids. The enzymes frequently expressed in sex steroid target tissues are, thus, potential drug targets in order to lower the local sex steroid concentrations. The present review summarises the recent data obtained for the role of HSD17B1, HSD17B2, HSD17B7 and HSD17B12 enzymes in various metabolic pathways and their physiological and pathophysiological roles as revealed by the recently generated genetically modified mouse models. Our data, together with that provided by others, show that, in addition to having a role in sex steroid metabolism, several of these HSD17B enzymes possess key roles in other metabolic processes: for example, HD17B7 is essential for cholesterol biosynthesis and HSD17B12 is involved in elongation of fatty acids. Additional studiesin vitroandin vivoare to be carried out in order to fully define the metabolic role of the HSD17B enzymes and to evaluate their value as drug targets.

scholarly journals Interrupted IGF-1 Feedback in GHRH Neurons and Somatotrophs Results in Impaired Weight Gain and Increased Energy Expenditure

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A52-A52
Author(s):  
Sarmed Al-Samerria ◽  
Bahaa Aloqaily ◽  
Ariel Negron ◽  
Fredric Edward Wondisford ◽  
Sally Radovick
Keyword(s):  
Growth Hormone ◽  
Energy Expenditure ◽  
Feedback Regulation ◽  
Total Activity ◽  
Co2 Production ◽  
Negative Feedback Regulation ◽  
Regulatory Pathways ◽  
Insulin Tolerance ◽  
Regulatory Effects

Abstract Growth hormone (GH) expression and release are thought to be primarily regulated by the counter-regulatory effects of growth hormone-releasing hormone (GHRH) and somatostatin (SST). Several reports generated in our lab and others suggest that there are other factors that regulate GH production, such as insulin-like growth factor 1 (IGF-I). Using GH-Cre recombinase targeting of the somatotroph-specific IGF-1R knockout (SIGFRKO) mouse model, we have previously demonstrated the role of IGF-1 signaling in negative feedback regulation of GH production. This model, however, presented with an incomplete phenotype, suggesting additional regulatory pathways in the hypothalamus. To provide insight into this mechanism, we have developed new transgenic mouse models that maintain the integrity of the hypothalamic-pituitary GH axis, with the single exception of IGF-IR deficiency in both hypothalamic GHRH neurons and somatotroph cells, termed GHRH-somatotroph IGF-1R knockout (G-SIFGRKO). Axiological assessments showed normal linear growth until week 14 of age, both male and female G-SIFGRKO mice presented with a significant reduction in growth velocity compared to control animals. Indirect calorimetry assessment performed at 12–14 weeks of age demonstrated that G-SIFGRKO mice had higher volume O2 consumption and lower volume CO2 production associated with increased energy expenditure than controls. The calculated respiratory exchange ratio was significantly reduced in G-SIFGRKO mice with no changes observed in either ambulatory or total activity. Furthermore, glucose and insulin tolerance tests showed no differences in glucose metabolism between G-SIFGRKO and controls. Collectively, these data provide further confirmation of the combinatorial role of IGF-1 signaling in regulating GH production and, for the first time, highlight a new GHRH-IGF-1R mediated pathway to regulate body growth and energy balance. Targeting this pathway has the potential to lead to a better understanding of the intersection between growth and metabolism and therapeutic approaches for obesity.

scholarly journals Genetically Modified Mouse Models Used for Studying the Role of the AT2Receptor in Cardiac Hypertrophy and Heart Failure

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Maria D. Avila ◽  
James P. Morgan ◽  
Xinhua Yan
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Cardiovascular System ◽  
Mouse Models ◽  
Genetically Modified ◽  
Cardiovascular Effects

The actions of Angiotensin II have been implicated in many cardiovascular conditions. It is widely accepted that the cardiovascular effects of Angiotensin II are mediated by different subtypes of receptors: AT1and AT2. These membrane-bound receptors share a part of their nucleic acid but seem to have different distribution and pathophysiological actions. AT1mediates most of the Angiotensin II actions since it is ubiquitously expressed in the cardiovascular system of the normal adult. Moreover AT2is highly expressed in the developing fetus but its expression in the cardiovascular system is low and declines after birth. However the expression of AT2appears to be modulated by pathological states such as hypertension, myocardial infarction or any pathology associated to tissue remodeling or inflammation. The specific role of this receptor is still unclear and different studies involvingin vivo and in vitroexperiments have shown conflicting data. It is essential to clarify the role of the AT2receptor in the different pathological states as it is a potential site for an effective therapeutic regimen that targets the Angiotensin II system. We will review the different genetically modified mouse models used to study the AT2receptor and its association with cardiac hypertrophy and heart failure.

Current and future approaches using genetically modified mice in endocrine research

2006 ◽  
Vol 291 (3) ◽  
pp. E429-E438 ◽  
Author(s):  
Rachel A. Davey ◽  
Helen E. MacLean
Keyword(s):  
Mouse Models ◽  
Target Genes ◽  
Genetically Modified ◽  
Advantages And Disadvantages ◽  
Genetically Modified Mice ◽  
The Many ◽  
Time Specific ◽  
Si Rna

Genetically modified mouse models have been used widely to advance our knowledge in the field of endocrinology and metabolism. A number of different approaches to generate genetically modified mice are now available, which provide the power to analyze the role of individual proteins in vivo. However, there are a number of points to be considered in the use and interpretation of these models. This review discusses the advantages and disadvantages involved in the generation and use of different genetically modified mouse models in endocrine research, including conventional techniques (e.g., overexpression, knockout, and knock-in models), tissue- and/or time-specific deletion of target genes [e.g., Cre- loxP and short interfering (si)RNA transgenic approaches], and gene-trap approaches to undertake functional genomics. This review also highlights the many factors that should be considered when assessing the phenotype of these mouse models, many of which are relevant to all murine physiological studies. These approaches are a powerful means by which to dissect the function of genes and are revolutionizing our understanding of endocrine physiology and metabolism.

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