Role of the GH/IGF-I axis in the growth retardation of weaver mice

The data of domestic and foreign literature on etiology, pathogenesis and intrauterine growth retardation diagnosis are presented in the paper. It highlights pathogenetic role of nitric oxide deficiency in case of obstetric complications and intrauterine growth retardation. Key words: intrauterine growth retardation (IUGR), system L-arginin–NO, obstetric complications.

Download Full-text

Differential Diagnosis of the Short IGF-I-Deficient Child with Apparently Normal Growth Hormone Secretion

Hormone Research in Paediatrics ◽

10.1159/000516407 ◽

2021 ◽

pp. 1-24

Author(s):

Jan M. Wit ◽

Sjoerd D. Joustra ◽

Monique Losekoot ◽

Hermine A. van Duyvenvoorde ◽

Christiaan de Bruin

Keyword(s):

Growth Hormone ◽

Differential Diagnosis ◽

Growth Hormone Secretion ◽

Normal Growth ◽

Stimulation Test ◽

Healthy Children ◽

Genetic Causes ◽

Gh Secretion ◽

Igf I

The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of GH1 or GHSR) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to GH1 variants) but less on the role of GHSR variants. Several genetic causes of (partial) GHI are known (GHR, STAT5B, STAT3, IGF1, IGFALS defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.

Download Full-text

Pathogenic role of Fgf23 in Dmp1-null mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90201.2008 ◽

2008 ◽

Vol 295 (2) ◽

pp. E254-E261 ◽

Cited By ~ 96

Author(s):

Shiguang Liu ◽

Jianping Zhou ◽

Wen Tang ◽

Rochelle Menard ◽

Jian Q. Feng ◽

...

Keyword(s):

Growth Retardation ◽

Matrix Protein ◽

Serum Levels ◽

Serum Phosphate ◽

Hypophosphatemic Rickets ◽

Null Mouse ◽

Matrix Mineralization ◽

Severe Growth ◽

Inactivating Mutations

Autosomal recessive hypophosphatemic rickets (ARHR), which is characterized by renal phosphate wasting, aberrant regulation of 1α-hydroxylase activity, and rickets/osteomalacia, is caused by inactivating mutations of dentin matrix protein 1 ( DMP1). ARHR resembles autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH), hereditary disorders respectively caused by cleavage-resistant mutations of the phosphaturic factor FGF23 and inactivating mutations of PHEX that lead to increased production of FGF23 by osteocytes in bone. Circulating levels of FGF23 are increased in ARHR and its Dmp1-null mouse homologue. To determine the causal role of FGF23 in ARHR, we transferred Fgf23 deficient/enhanced green fluorescent protein (eGFP) reporter mice onto Dmp1-null mice to create mice lacking both Fgf23 and Dmp1. Dmp1−/− mice displayed decreased serum phosphate concentrations, inappropriately normal 1,25(OH)2D levels, severe rickets, and a diffuse form of osteomalacia in association with elevated Fgf23 serum levels and expression in osteocytes. In contrast, Fgf23−/− mice had undetectable serum Fgf23 and elevated serum phosphate and 1,25(OH)2D levels along with severe growth retardation and focal form of osteomalacia. In combined Dmp1−/−/Fgf23−/−, circulating Fgf23 levels were also undetectable, and the serum levels of phosphate and 1,25(OH)2D levels were identical to Fgf23−/− mice. Rickets and diffuse osteomalacia in Dmp1-null mice were transformed to severe growth retardation and focal osteomalacia characteristic of Fgf23-null mice. These data suggest that the regulation of extracellular matrix mineralization by DMP1 is coupled to renal phosphate handling and vitamin D metabolism through a DMP1-dependent regulation of FGF23 production by osteocytes.

Download Full-text

Regulation of immature cartilage growth by IGF-I, TGF-β1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network

Biomechanics and Modeling in Mechanobiology ◽

10.1007/s10237-007-0096-8 ◽

2007 ◽

Vol 7 (4) ◽

pp. 263-276 ◽

Cited By ~ 26

Author(s):

Anna Asanbaeva ◽

Koichi Masuda ◽

Eugene J-M. A. Thonar ◽

Stephen M. Klisch ◽

Robert L. Sah

Keyword(s):

Fixed Charge ◽

Collagen Network ◽

Cartilage Growth ◽

Metabolic Balance ◽

Igf I ◽

Tgf Β1

Download Full-text

Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.4.e614 ◽

1996 ◽

Vol 270 (4) ◽

pp. E614-E620 ◽

Cited By ~ 16

Author(s):

E. Svanberg ◽

H. Zachrisson ◽

C. Ohlsson ◽

B. M. Iresjo ◽

K. G. Lundholm

Keyword(s):

Protein Synthesis ◽

Skeletal Muscles ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Oral Feeding ◽

Myofibrillar Proteins ◽

Diabetic Mice ◽

Igf I ◽

Stimulation Of

The aim was to evaluate the role of insulin and insulin-like growth factor I (IGF-I) in activation of muscle protein synthesis after oral feeding. Synthesis rate of globular and myofibrillar proteins in muscle tissue was quantified by a flooding dose of radioactive phenylalanine. Muscle tissue expression of IGF-I mRNA was measured. Normal (C57 Bl) and diabetic mice (type I and type II) were subjected to an overnight fast (18 h) with subsequent refeeding procedures for 3 h with either oral chow intake or provision of insulin, IGF-I, glucose, and amino acids. Anti-insulin and anti-IGF-I were provided intraperitoneally before oral refeeding in some experiments. An overnight fast reduced synthesis of both globular (38 +/- 3%) and myofibrillar proteins (54 +/- 3%) in skeletal muscles, which was reversed by oral refeeding. Muscle protein synthesis, after starvation/ refeeding, was proportional and similar to changes in skeletal muscle IGF-I mRNA expression. Diabetic mice responded quantitatively similarly to starvation/refeeding in muscle protein synthesis compared with normal mice (C57 Bl). Both anti-insulin and anti-IGF-I attenuated significantly the stimulation of muscle protein synthesis in response to oral feeding, whereas exogenous provision of either insulin or IGF-I to overnight-starved and freely fed mice did not clearly stimulate protein synthesis in skeletal muscles. Our results support the suggestion that insulin and IGF-I either induce or facilitate the protein synthesis machinery in skeletal muscles rather than exerting a true stimulation of the biosynthetic process during feeding.

Download Full-text

The role of insulin-like growth factor-I (IGF-I) and estradiol in rabbit corpus luteum progesterone production

Endocrine ◽

10.1007/bf02738805 ◽

1997 ◽

Vol 6 (1) ◽

pp. 73-77 ◽

Cited By ~ 4

Author(s):

Serena H. Chen ◽

Vanna Zanagnolo ◽

Sangchai Preutthipan ◽

Kenneth P. Roberts ◽

Sandra B. Goodman ◽

...

Keyword(s):

Growth Factor ◽

Corpus Luteum ◽

Insulin Like Growth Factor ◽

Factor I ◽

Progesterone Production ◽

Igf I ◽

Growth Factor I

Download Full-text

IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH

Acta Endocrinologica ◽

10.1530/eje.0.1440237 ◽

2001 ◽

pp. 237-243 ◽

Cited By ~ 13

Author(s):

X Zhou ◽

KY Loke ◽

CC Pillai ◽

HK How ◽

HK Yap ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Growth Retardation ◽

Bone Age ◽

Gh Treatment ◽

Igf Binding Proteins ◽

Steroid Dependent ◽

Igf I ◽

Igf Binding ◽

Pre Treatment ◽

Igfbp 3

OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.

Download Full-text

Differential Impacts of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) in Epithelial IGF-Induced Lung Cancer Development

Endocrinology ◽

10.1210/en.2010-0693 ◽

2011 ◽

Vol 152 (6) ◽

pp. 2164-2173 ◽

Cited By ~ 13

Author(s):

Woo-Young Kim ◽

Mi-Jung Kim ◽

Hojin Moon ◽

Ping Yuan ◽

Jin-Soo Kim ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tumor ◽

Binding Protein ◽

Cancer Development ◽

Lung Carcinogenesis ◽

Tobacco Carcinogen ◽

Igf I ◽

The Impact ◽

Igfbp 3

The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.

Download Full-text