GH1
Somatotropin precursor (Growth hormone) (GH) (GH-N) (Growth hormone 1) (Pituitary growth hormone)
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Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability. As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance. Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82-0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits. Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Anthropometry
- Cohort Studies
- Female
- Gene Frequency
- Genetic Association Studies
- Genotyping Techniques
- Hand Strength
- Health
- Human Growth Hormone
- Humans
- Insulin-Like Growth Factor I
- Insulin-Like Growth Factor II
- Male
- Middle Aged
- Motor Activity
- Polymorphism, Single Nucleotide
- Postural Balance
- Sex Characteristics
- Signal Transduction
- United Kingdom
Our aim was to investigate the long-term effects of intramuscular injection of rAAV2/1-CMV-GH1 viral particles on GH1 expression in normal adult male rats. We found that specific and sustained GH1 expression did not improve muscle exercise performance despite inducing local muscle hypertrophy. Injection of rAAV2/1-CMV-GH1 had some systemic effects on the liver and heart and on lipid metabolism in the healthy rats. Serum levels of hGH (human growth hormone), insulin, glucose and leptin increased significantly, which might induce insulin resistance. The serum concentration of IGF-1 (insulin-like growth factor 1), IGF-BP3 (insulin-like growth factor binding protein 3) and PIIINP (N-terminal propeptide of type III procollagen) markedly increased at 24 weeks after injection of GH1. In conclusion, GH1 expression driven by AAV2/1 in normal animals did not improve muscle strength but did increase muscle mass and may have systemic effects in healthy animals.
MeSH Terms
- Aging
- Animals
- Dependovirus
- Gene Transfer Techniques
- Growth Hormone
- Human Growth Hormone
- Hypertrophy
- Insulin-Like Growth Factor Binding Protein 3
- Insulin-Like Growth Factor I
- Lipids
- Liver
- Male
- Muscle, Skeletal
- Myocardium
- Rats
- Rats, Sprague-Dawley
- Recombination, Genetic
- Reproducibility of Results
Evidence is accumulating that aging is hormonally regulated by an evolutionarily conserved insulin/IGF-1 signalling (IIS) pathway. Mutations in IIS components affect lifespan in Caenorhabditis elegans, Drosophila melanogaster and mice. Most long-lived IIS mutants also show increased resistance to oxidative stress. In D. melanogaster and mice, the long-lived phenotype of several IIS mutants is restricted to females. Here, we analysed the relationship between IIS signalling, body height and longevity in humans in a prospective follow-up study. Based on the expected effects (increased or decreased signalling) of the selected variants in IIS pathway components (GHRHR, GH1, IGF1, INS, IRS1), we calculated composite IIS scores to estimate IIS pathway activity. In addition, we analysed the relative impact on lifespan and body size of the separate variants in multivariate models. In women, lower IIS scores are significantly associated with lower body height and improved old age survival. Multivariate analyses showed that these results were most pronounced for the GH1 SNP, IGF1 CA repeat and IRS1 SNP. In females, for variant allele carriers of the GH1 SNP, body height was 2 cm lower (P = 0.007) and mortality 0.80-fold reduced (P = 0.019) when compared with wild-type allele carriers. Thus, in females, genetic variation causing reduced IIS activation is beneficial for old age survival. This effect was stronger for the GH1 SNP than for variation in the conserved IIS genes that were found to affect longevity in model organisms.
MeSH Terms
- Aged
- Aged, 80 and over
- Body Height
- Female
- Human Growth Hormone
- Humans
- Insulin
- Insulin Receptor Substrate Proteins
- Insulin-Like Growth Factor I
- Linkage Disequilibrium
- Longevity
- Male
- Multivariate Analysis
- Phosphoproteins
- Polymorphism, Single Nucleotide
- Receptors, Neuropeptide
- Receptors, Pituitary Hormone-Regulating Hormone
Like many poecilotherms, salmonids exhibit seasonal variations of growth rate in relation with seasonal temperatures and plasma GH level. However, temperature alters other parameters like food intake, which may directly modify the level of plasma GH. In order to determine whether temperature regulates plasma GH levels independently of nutritional status, fish were reared at 8, 12, or 16 degrees C and either fed ad libitum (fish with different food intake) to determine the global effect of temperature, or with the same ration (1.2%/body weight) to observe the temperature effect in fish with the same growth rate. Plasma insulin level was inversely proportional to the temperature (8, 12, and 16 degrees C) in fish fed ad libitum (12.1 /-0.3 ng/ml, 10.9 /-0.3 ng/ml, 9.5 /-0.4 ng/ml; P<0.001) and in restricted fish (14.0 /-0.3 ng/ml, 11.3 /-0.3 ng/ml, 10.0 /-0.2 ng/ml; P<0.0001), probably due to a prolonged nutrient absorption, and delayed recovery of basal insulin level at low temperature. Conversely, temperature did not affect plasma T3 level of fish fed ad libitum (2.5 /-0.2 ng/ml, 2.4 /-0.1 ng/ml, 2.5 /-0.1 ng/ml at 8, 12, and 16 degrees C) while fish fed with the same ration present less T3 at 16 degrees C than at 8 degrees C (1.83 /-0.1 ng/ml versus 1.2 /-0.1 ng/ml; P<0.001) throughout the experiment; these observations indicate that different plasma T3 levels reflect the different nutritional status of the fish. The levels of GH1 and GH2 mRNA, and GH1/GH2 ratio were not different for whatever the temperature or the nutritional status. Pituitary GH content, of fish fed ad libitum did not exhibit obvious differences at 8, 12, or 16 degrees C (254 /-9 ng/g bw, 237 /-18 ng/g bw, 236 /-18 ng/g bw), while fish fed with the same ration have higher pituitary GH contents at 16 degrees C than at 8 degrees C (401 /-30 ng/g bw versus 285 /-25 ng/g bw; P<0.0001). Interestingly, high temperature strongly increases plasma GH levels (2.5 /-0.3 ng/ml at 8 degrees C versus 4.8 /-0.6 ng/ml at 16 degrees C; P<0.0001) to the same extent in both experiments, since at a given temperature average plasma GH was similar between fish fed ad libitum or a restricted diet. Our results, demonstrate that temperature regulates plasma GH levels specifically but not pituitary GH content, nor the levels of GH1 and GH2 mRNA. In addition no differential regulation of both GH genes was evidenced whatever the temperature.
MeSH Terms
- Aging
- Animal Nutritional Physiological Phenomena
- Animals
- Environment
- Growth Hormone
- Insulin
- Oncorhynchus mykiss
- Pituitary Gland
- Protein Isoforms
- RNA, Messenger
- Temperature
- Triiodothyronine
Growth hormone, GH1, or growth hormone and prolactin, GH3, secreting tumors were induced in 1 week old female Wistar-Furth rats and 17 week old female Wistar-Furth rats. At 11 or 30 weeks of age the parametrial fat pad (PFP) was weighed and a portion fixed with osmium tetroxide for cell quantitation by a Coulter counter technique. Tumor induction increased the body weight of both young and mature rats by 50 and 100% respectively when compared to age matched controls. Serum GH was elevated about 100 fold in both young and old treated rats when compared to controls. Tumor induction decreased the weight of the PFP in both young and old rats when compared to controls but the effect was only significant in the GH3 tumor bearing rats weights. The PFP made up a much smaller percentage of the body weight in all the treated groups when compared to respective age matched controls. Mean PFP adipocyte number was not affected by treatment or age. Tumor induction decreased the mean diameter and mean volume of adipocytes in both young and old rats of both treatment groups compared to age matched controls. The distribution of adipocytes by cell diameter was shifted toward smaller cells in the tumor-bearing rats. In conclusion, induction of GH1 or GH3 tumors elevated serum GH concentrations, increased body weight and decreased relative fat pad weight but did not affect adipocyte cell number. Hence, the proposed adipogenic function of GH does not appear to function in this model in vivo.
MeSH Terms
- Adipose Tissue
- Aging
- Animals
- Cell Line
- Growth Hormone
- Pituitary Neoplasms
- Rats