GHRHR
Growth hormone-releasing hormone receptor precursor (GHRH receptor) (Growth hormone-releasing factor receptor) (GRF receptor) (GRFR)
Publications[править]
Biallelic mutations in the GHRH receptor ([[GHRHR]]) gene ([[GHRHR]]) are a frequent cause of isolated GH deficiency (IGHD). Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a [[GHRHR]] mutation might be associated with a subclinical phenotype. We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null [[GHRHR]] mutation. We compared 76 adult subjects (age, 25-75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type [[GHRHR]] allele (WT/WT). We found no difference in adult height and sd score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups. Heterozygosity for a null [[GHRHR]] mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I.
MeSH Terms
- Adult
- Aged
- Aging
- Body Composition
- Body Height
- Body Mass Index
- Brazil
- Female
- Heterozygote
- Humans
- Insulin Resistance
- Insulin-Like Growth Factor I
- Male
- Middle Aged
- Mutation
- Phenotype
- Receptors, Neuropeptide
- Receptors, Pituitary Hormone-Regulating Hormone
Genetic interventions that accelerate or retard aging in mice are crucial in advancing our knowledge over mammalian aging. Yet determining if a given intervention affects the aging process is not straightforward since, for instance, many disease-causing mutations may decrease life span without affecting aging. In this work, we employed the Gompertz model to determine whether several published interventions previously claimed to affect aging in mice do indeed alter the aging process. First, we constructed age-specific mortality tables for a number of mouse cohorts used in longevity experiments and calculated the rate at which mortality increases with age. Estimates of age-independent mortality were also calculated. We found no statistical evidence that GHRHR, IGF1R, INSR, PROP1, or TRX delay or that ATM TERC, BubR1, klotho, LMNA, PRDX1, p53, WRN TERC, or TOP3B accelerate mouse aging. Often, changes in the expression of these genes affected age-independent mortality and so they may prove useful to other aspects of medicine. We found statistical evidence that C/EBP, MSRA, SHC1, growth hormone, GHR, PIT1, and PolgA may influence aging in mice. These results were interpreted together with age-related physiological and pathological changes and provide novel insights regarding the role of several genes in the mammalian aging process.
MeSH Terms
- Aging
- Animals
- Gene Expression
- Genes
- Mice
- Mice, Mutant Strains
- Models, Animal
- Mortality