A5054006122- Growth Hormone and Insulin-like Growth Factors
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Animal Genetics and Reproduction
- Cancer, Hypoxia, and Metabolism
- Regulation of Appetite and Obesity
- Birth, Development, and Health
- Pancreatic function and diabetes
- Pituitary Gland Disorders and Treatments
- Virus-based gene therapy research
- Metabolism, Diabetes, and Cancer
- Digestive system and related health
- Lipid metabolism and disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Muscle Physiology and Disorders
- Diabetes and associated disorders
- Thyroid Disorders and Treatments
- CRISPR and Genetic Engineering
- Liver Disease Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Muscle metabolism and nutrition
- Viral Infectious Diseases and Gene Expression in Insects
- FOXO transcription factor regulation
- RNA Interference and Gene Delivery
Ohio University
2016-2025
Biotechnology Institute
2015-2024
Edison (Italy)
2004-2024
Wayne State University
2022-2024
Ohio University Lancaster
1992-2024
Vanderbilt University
2024
Maastricht University
2022
University of Gothenburg
2021
Aarhus University Hospital
2011-2018
Aarhus University
1999-2018
Laron syndrome [growth hormone (GH) insensitivity syndrome] is a hereditary dwarfism resulting from defects in the GH receptor (GHR) gene. GHR deficiency has not been reported mammals other than humans. Many aspects of dysfunction remain unknown because ethical and practical limitations studying To create mammalian model for this disease, we generated mice bearing disrupted GHR/binding protein (GHR/BP) gene through homologous targeting approach. Homozygous GHR/BP knockout showed severe...
GH has many biological roles, including promotion of growth. Most, if not all, its roles are achieved through interaction with receptor. We chose to study the effects loss signaling on growth and aging in a mouse model for Laron Syndrome (LS) which GHR/BP gene been disrupted. observed that mice homozygous disruption (−/−) were significantly smaller than normal wild-type (+/+) as well heterozygous disruption, even at 1.5 yr age. IGF-I levels also lower −/− remained low aged. IGFBP-3 severely...
Abstract GH participates in growth, metabolism, and cellular differentiation. To study these roles, we previously generated two different dwarf mouse lines, one expressing a antagonist (GHA) the other having disrupted receptor binding protein gene (GHR −/−). In this compared lines same genetic background (C57BL/6J). One of most striking differences between was their weight gain profile after weaning. The weights GHA dwarfs gradually approached controls over time, but GHR −/− remained low...
Retinal neovascularization is the major cause of untreatable blindness. The role growth hormone (GH) in ischemia-associated retinal was studied transgenic mice expressing a GH antagonist gene and normal given an inhibitor secretion (MK678). inhibited these inverse proportion to serum levels downstream effector, insulin-like factor–I (IGF-I). Inhibition reversed with exogenous IGF-I administration. inhibition did not diminish hypoxia-stimulated vascular endothelial factor (VEGF) or VEGF...
Abstract Objective The aim of the Acromegaly Consensus Group was to revise and update consensus on diagnosis treatment acromegaly comorbidities last published in 2013. Participants Group, convened by 11 Steering Committee members, consisted 45 experts medical surgical management acromegaly. authors received no corporate funding or remuneration. Evidence This evidence-based developed using Grading Recommendations, Assessment, Development, Evaluation (GRADE) system describe both strength...
Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety efficacy children adults subject to considerable scrutiny. In 2001, a statement from the Research Society (GRS) concluded 'for approved indications, is safe'; however, highlighted number of areas on-going surveillance long-term safety, including cancer risk, impact on glucose homeostasis, high dose pharmacological rhGH treatment. Over intervening there have publications addressing with regard mortality,...
Abstract Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight becomes increasingly difficult with regain commonly occurring most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and receptor (GHR) ablation AgRP cells mitigates highly characteristic hypothalamic induced by loss....
Growth hormone (GH) regulates both bone growth and remodeling, but it is unclear whether these actions are mediated directly by the GH receptor (GHR) and/or IGF-I signaling. The of transduced Jak/Stat signaling pathway via Stat5, which thought to regulate expression. To determine respective roles GHR in we examined bones wild-type, knockout (GHR–/–), Stat5ab–/–, GHR–/– mice treated with IGF-I. Reduced mice, due a premature reduction chondrocyte proliferation cortical growth, was detected...
Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf mutant stock are resistant, in vitro, to cytotoxic effects H(2)O(2), cadmium, UV light, paraquat, and heat. We show here similar resistance profiles seen cells a related mutant, Ames mouse, growth hormone receptor-null resistant but not cadmium. Resistance H(2)O(2) 1-wk-old or normal mice, thus donors reflects developmental processes, presumably dependent, take place...
Growth hormone (GH) plays a pivotal role in growth and metabolism, with promotion mostly attributed to generation of insulin-like factor I (IGF-I) liver or at local sites GH action, whereas the metabolic effects are considered be intrinsic itself. To distinguish from those IGF-I, we developed Cre-lox-mediated model tissue-specific deletion receptor (GHR). Near total GHR (GHRLD) had no effect on body bone linear despite >90% suppression circulating IGF-I; however, density was significantly...
Liver IGF-1-deficient (LID) mice have a 75% reduction in circulating IGF-1 levels and, as result, fourfold increase growth hormone (GH) secretion. To block GH action, LID were crossed with antagonist (GHa) transgenic mice. Inactivation of action the resulting + GHa led to decreased blood glucose and insulin improved peripheral sensitivity. Hyperinsulinemic-euglycemic clamp studies showed that exhibit severe resistance. In contrast, expression transgene enhanced sensitivity increased...
Although studies of Ames and Snell dwarf mice have suggested possible important roles the growth hormone (GH)/insulin-like factor-1 (IGF-1) axis in aging age-related diseases, results cannot rule out possibility other hormonal changes playing an role life extension exhibited by these mice. Therefore, receptor/binding protein (GHR/BP) knockout (KO) would be valuable animals to directly assess somatotropic diseases because primary change is due GH/IGF-1 deficiency. Our pathological findings...
Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and promoting postnatal growth. GHR gene-deficient (GHR(-/-)) mice exhibit severe growth retardation proportionate dwarfism. To assess the physiological relevance of hormone actions, GHR(-/-) were used to investigate their phenotype glucose pancreatic islet function. Adult exhibited significant reductions levels blood insulin, as well insulin mRNA accumulation. Immunohistochemical analysis...
In mammalian cells, Sprecher has proposed that the synthesis of long-chain PUFA from 20-carbon substrates involves two consecutive elongation steps, a delta6-desaturation step followed by retroconversion (Sprecher, H., Biochim. Biophys. Acta 1486, 219-231, 2000). We searched database using translated sequence human elongase ELOVL5, whose encoded enzyme elongates monounsaturated and polyunsaturated FA, as query to identify enzyme(s) involved in very long chain PUFA. The search led isolation...
To determine the importance of third alpha-helix in bovine growth hormone (bGH) relative to growth-related biological activities, following experimental approach was used: (i) mutagenesis helix III bGH generate an idealized amphiphilic helix; (ii) vitro expression analyses mutated gene cultured mouse L cells; (iii) liver membrane binding studies wild-type and bGH; (iv) transgenic mouse. An altered (pBGH10 delta 6-M8) generated that encodes changes: glutamate-117 leucine, glycine-119...