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Annales D'endocrinologie Jun 2016Firstly discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in... (Review)
Review
Firstly discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a metalloproteinase that is able to specifically cleave three insulin-like growth factor binding proteins (IGFBPs): IGFBP-2, -4 and -5. PAPP-A binds tightly to glycosaminoglycans present on the surface of cells, thus functioning within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. Pro-MBP and stanniocalcin-2 (STC2) appear to be the main inhibitors of PAPP-A activity, by forming a covalent complex with the protease. According to in vivo experiments, IGFBP-4 is believed to be the main PAPP-A substrate to regulate IGF bioavailability. The regulation of PAPP-A includes transcriptional control of its gene, competing reactions with other IGFBPs potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signalling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible.
Topics: Animals; Female; Humans; Pregnancy; Pregnancy-Associated Plasma Protein-A; Signal Transduction; Somatomedins
PubMed: 27155776
DOI: 10.1016/j.ando.2016.04.015 -
Mutation Research. Reviews in Mutation... 2017Human papillomaviruses (HPV) infect and replicate in stratified epithelium at cutaneous and mucosal surfaces. The proliferation and maintenance of keratinocytes, the... (Review)
Review
Human papillomaviruses (HPV) infect and replicate in stratified epithelium at cutaneous and mucosal surfaces. The proliferation and maintenance of keratinocytes, the cells which make up this epithelium, are controlled by a number of growth factor receptors such as the keratinocyte growth factor receptor (KGFR, also called fibroblast growth factor receptor 2b (FGFR2b)), the epithelial growth factor receptor (EGFR) and the insulin-like growth factor receptors 1 and 2 (IGF1R and IGF2R). In this review, we will delineate the mutation, gene transcription, translation and processing of the IGF axis within HPV associated cancers. The IGFs are key for developmental and postnatal growth of almost all tissues; we explore whether this crucial axis has been hijacked by HPV.
Topics: Cell Proliferation; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Keratinocytes; Neoplasms; Papillomaviridae; Receptor, Fibroblast Growth Factor, Type 2; Receptor, IGF Type 1; Receptor, IGF Type 2; Receptors, Somatomedin; Somatomedins
PubMed: 28528691
DOI: 10.1016/j.mrrev.2017.01.002 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2019Insulin-like growth factors(IGFs)are polypeptides structurally homologous to insulin.By binding to membrane tyrosine receptors,they regulate the... (Review)
Review
Insulin-like growth factors(IGFs)are polypeptides structurally homologous to insulin.By binding to membrane tyrosine receptors,they regulate the proliferation,differentiation,apoptosis,growth,and development of body cells and are involved in the pathogenesis of tumors and other diseases.In recent years,more research on IGFs of dermatosis increased.This article reviews recent research advances in IGFs and its relationship with dermatosis.
Topics: Humans; Peptides; Skin Diseases; Somatomedins
PubMed: 31282339
DOI: 10.3881/j.issn.1000-503X.11162 -
Handbook of Experimental Pharmacology 2020In this chapter, we want to give an overview on what we have learned from more than 30 years ago on the use of recombinant human growth hormone (rhGH) and later... (Review)
Review
In this chapter, we want to give an overview on what we have learned from more than 30 years ago on the use of recombinant human growth hormone (rhGH) and later recombinant human IGF-1 which was introduced for the treatment of short children and what are the safety issues concerned with this treatment. However, rhGH is used not solely in conditions where short stature is the consequence of GH deficiency but also in various disorders without a proven GH deficiency. In clinical studies, growth responses to various forms of rhGH therapy were analyzed, adding to our concept about the physiology of growth. Most patients under rhGH treatment show a considerable short-term effect; however, the long-term gain of height in a child obtained by a year-long treatment until final height remains controversial in some of the growth disorders that have been treated with rhGH or IGF-1. Today the first studies on the long-term safety of rhGH treatment have been published and raising some questions whether this treatment is similarly safe for all the patient groups treated with rhGH. Although there is a long-standing safety record for these hormone replacement therapies, in the face of the considerable costs involved, the discussion about the risk to benefit ratio is continuing. Newer developments of rhGH treatment include long-term preparations, which have only to be injected once a week. Although some of these drugs already have proven their non-inferiority to conventional rhGH treatment, we have to await further results to see whether they show improvements in treatment adherence of the patients and prove their long-term safety.
Topics: Child; Dwarfism, Pituitary; Growth Disorders; Hormone Replacement Therapy; Human Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 31932988
DOI: 10.1007/164_2019_337 -
Cytokine & Growth Factor Reviews Jun 2015Upregulation of IGF2 occurs in both childhood and adult malignancies. Its overexpression is associated with resistance to chemotherapy and worse prognosis. IGF2 promoter... (Review)
Review
Upregulation of IGF2 occurs in both childhood and adult malignancies. Its overexpression is associated with resistance to chemotherapy and worse prognosis. IGF2 promoter usage is developmentally regulated; however, malignant tissues are characterized by re-activation of the fetal IGF2 promoters, especially P3. In this review, we describe the mechanisms of IGF2 signaling and regulation in normal and malignant tissues and their clinical implications.
Topics: Animals; Drug Resistance, Neoplasm; Humans; Insulin-Like Growth Factor II; Neoplasms; Signal Transduction
PubMed: 25704323
DOI: 10.1016/j.cytogfr.2015.01.002 -
Journal of Molecular Endocrinology Jul 2018The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily... (Review)
Review
The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily among endocrinologists who study growth and metabolism. The advancement of molecular endocrinology over the past four decades enables investigators to re-examine and refine the established somatomedin hypothesis. Specifically, gene deletions, transgene overexpression or more recently, cell-specific gene-ablations, have enabled investigators to study the effects of the and genes in temporal and spatial manners. The GH/IGF axis, acting in an endocrine and autocrine/paracrine fashion, is the major axis controlling skeletal growth. Studies in rodents have clearly shown that IGFs regulate bone length of the appendicular skeleton evidenced by changes in chondrocytes of the proliferative and hypertrophic zones of the growth plate. IGFs affect radial bone growth and regulate cortical and trabecular bone properties via their effects on osteoblast, osteocyte and osteoclast function. Interactions of the IGFs with sex steroid hormones and the parathyroid hormone demonstrate the significance and complexity of the IGF axis in the skeleton. Finally, IGFs have been implicated in skeletal aging. Decreases in serum IGFs during aging have been correlated with reductions in bone mineral density and increased fracture risk. This review highlights many of the most relevant studies in the IGF research landscape, focusing in particular on IGFs effects on the skeleton.
Topics: Animals; Chondrocytes; Humans; Osteoblasts; Osteoclasts; Skeleton; Somatomedins
PubMed: 29626053
DOI: 10.1530/JME-17-0298 -
Biomolecules Feb 2021The insulin-like growth factor (IGF) system is a dynamic network of proteins, which includes cognate ligands, membrane receptors, ligand binding proteins and functional... (Review)
Review
The insulin-like growth factor (IGF) system is a dynamic network of proteins, which includes cognate ligands, membrane receptors, ligand binding proteins and functional downstream effectors. It plays a critical role in regulating several important physiological processes including cell growth, metabolism and differentiation. Importantly, alterations in expression levels or activation of components of the IGF network are implicated in many pathological conditions including diabetes, obesity and cancer initiation and progression. In this review we will initially cover some general aspects of IGF action and regulation in cancer and then focus in particular on the role of transcriptional regulators and novel interacting proteins, which functionally contribute in fine tuning IGF1R signaling in several cancer models. A deeper understanding of the biological relevance of this network of IGF1R modulators might provide novel therapeutic opportunities to block this system in neoplasia.
Topics: Disease Progression; Humans; Ligands; Neoplasms; Protein Binding; Receptor, IGF Type 1; Signal Transduction; Somatomedins
PubMed: 33673232
DOI: 10.3390/biom11020273 -
Molecular and Cellular Endocrinology May 2024Insulin-like peptides are a group of hormones crucial for regulating metabolism, growth, and development in animals. Invertebrates, such as C. elegans, have been... (Review)
Review
Insulin-like peptides are a group of hormones crucial for regulating metabolism, growth, and development in animals. Invertebrates, such as C. elegans, have been instrumental in understanding the molecular mechanisms of insulin-like peptides. Here, we review the 40 insulin-like peptide genes encoded in the C. elegans genome. Despite the large number, there is only one C. elegans insulin-like peptide receptor, called DAF-2. The insulin and insulin-like growth factor signaling (IIS) pathway is evolutionarily conserved from worms to humans. Thus C. elegans provides an excellent model to understand how these insulin-like peptides function. C. elegans is unique in that it possesses insulin-like peptides that have antagonistic properties, unlike all human insulin-like peptides, which are agonists. This review provides an overview of the current literature on C. elegans insulin-like peptide structures, processing, tissue localization, and regulation. We will also provide examples of insulin-like peptide signaling in C. elegans during growth, development, germline development, learning/memory, and longevity.
Topics: Animals; Humans; Caenorhabditis elegans; Insulin-Like Peptides; Insulin; Somatomedins; Signal Transduction; Caenorhabditis elegans Proteins; Longevity; Forkhead Transcription Factors
PubMed: 38346555
DOI: 10.1016/j.mce.2024.112173 -
Pediatric Endocrinology Reviews : PER Dec 2015The insulin-like growth factor (IGF) system is essential for normal growth and development, and its perturbation is implicated in a number of diseases. IGF activity is... (Review)
Review
The insulin-like growth factor (IGF) system is essential for normal growth and development, and its perturbation is implicated in a number of diseases. IGF activity is finely regulated by a family of six high-affinity IGF binding proteins (IGFBPs). 1GFBPs usually inhibit IGF actions but may enhance them under certain conditions. Additionally, IGFBPs bind non-IGF ligands in the extracellular space, cell membrane, cytoplasm and nucleus, thereby modulating cell proliferation, survival and migration in an IGF-independent manner. IGFBP activity is regulated by transcriptional mechanisms as well as by post-translational modifications and proteolysis. Understanding the balance between the various actions of IGFBPs in vivo may lead to novel insights into disease processes and possible IGFBP-based therapeutics.
Topics: Animals; Cell Physiological Phenomena; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Protein 4; Insulin-Like Growth Factor Binding Protein 5; Insulin-Like Growth Factor Binding Protein 6; Insulin-Like Growth Factor Binding Proteins; Molecular Structure; Somatomedins
PubMed: 26841640
DOI: No ID Found -
Nestle Nutrition Institute Workshop... 2018Breastfed infants have a growth pattern that is different from formula-fed infants, which is regarded as the optimal growth pattern. Breastfed infants increase more in... (Comparative Study)
Comparative Study Review
Breastfed infants have a growth pattern that is different from formula-fed infants, which is regarded as the optimal growth pattern. Breastfed infants increase more in weight, length, and BMI during the first 2-3 months of life and then have a slower growth velocity up to 12 months. They also have a higher accumulation of fat during early infancy. Breastfed infants have lower levels of circulating IGF-I and insulin, which could be part of the explanation of their growth pattern. Many studies and meta-analyses have examined the association between breastfeeding and later obesity. Most find a moderate reduction in the risk of later obesity, but it has been argued that this could be biased due to residual confounding and reverse causation. From studies in low- and middle-income countries randomizing women to breastfeeding promotion, there was only little effect on early growth. Recent studies have found associations between breast milk composition (total fat, protein, human milk oligosaccharides, adiponectin, leptin, and insulin) and growth. However, the studies are few, and the results are inconsistent. More studies, including studies of maternal factors influencing breast milk composition, are needed to better understand how breastfeeding influences current and later growth and thereby short- and long-term health.
Topics: Adiponectin; Body Composition; Body Height; Body Mass Index; Body Weight; Breast Feeding; Child; Child, Preschool; Fats; Female; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Leptin; Milk Proteins; Milk, Human; Obesity; Oligosaccharides; Poverty; Somatomedins; Weight Gain
PubMed: 29991033
DOI: 10.1159/000486493