ReviewJournal of clinical research in pediatric endocrinology2017
Novel Modulators of the Growth Hormone - Insulin-Like Growth Factor Axis: Pregnancy-Associated Plasma Protein-A2 and Stanniocalcin-2.
Review in Journal of clinical research in pediatric endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Rare protein-coding variation and the genetic architecture of height in >1.4 million individuals.medRxiv : the preprint server for health sciences · 2026Article
- Paracrine IGFBP3 spatially coordinates IGF signaling to induce myocardial regeneration in mice.Journal of molecular and cellular cardiology · 2025Article
- Diagnostic Challenges of Short Stature and Growth Hormone Insufficiency Across Different Genetic Etiologies.Biomedicines · 2025Review
- IGFBP3 modulation of tumor pathogenesis and cell signaling pathways (Review).Oncology letters · 2025Review
- Pregnancy associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) but not PAPP-A are associated with circulating total IGF-1 in a human adult population.Scientific reports · 2024Article
- Cryo-EM structure of human PAPP-A2 and mechanism of substrate recognition.Communications chemistry · 2023Article
- Time-Dependent Changes in Muscle IGF1-IGFBP5-PAPP System after Sciatic Denervation.International journal of molecular sciences · 2023Article
- Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins.Frontiers in endocrinology · 2023Article
- Structure of the PAPP-ANature communications · 2022Article
- PAPPA2 mutation as a novel indicator stratifying beneficiaries of immune checkpoint inhibitors in skin cutaneous melanoma and non-small cell lung cancer.Cell proliferation · 2022Article
- Article
- Genetic causes of growth hormone insensitivity beyond GHR.Reviews in endocrine & metabolic disorders · 2021Review
- Proenkephalin Decreases in Cerebrospinal Fluid with Symptom Progression of Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Article
- Abnormal proinflammatory and stressor environmental with increased the regulatory cellular IGF-1/PAPP-A/STC and Wnt-1/β-Catenin canonical pathway in placenta of women with Chronic venous Disease during Pregnancy.International journal of medical sciences · 2021Observational
- Genetic Screening for Growth Hormone Therapy in Children Small for Gestational Age: So Much to Consider, Still Much to Discover.Frontiers in endocrinology · 2021Review
- The metalloproteinase Papp-aa controls epithelial cell quiescence-proliferation transition.eLife · 2020Article
- Deimination Protein Profiles inFrontiers in immunology · 2020Article
- Abnormal expression of Pappa2 gene may indirectly affect mouse hip development through the IGF signaling pathway.Endocrine · 2019Article
- A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes.Molecular ecology resources · 2019Article
- Low IGF-I Bioavailability Impairs Growth and Glucose Metabolism in a Mouse Model of Human PAPPA2 p.Ala1033Val Mutation.Endocrinology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Growth hormone (GH) and its mediator, insulin-like growth factor-1 (IGF-1), play a critical role in human growth. In circulation, IGF-1 is found in a ternary complex with IGF binding proteins (IGFBPs) and acid labile subunit (ALS) but little attention has been paid to the regulation of IGF-1 bioavailability. Recently, pregnancy-associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) were identified as novel modulators of IGF-I bioavailability. PAPP-A2 is a protease which cleaves IGFBP-3 and -5, while STC2 inhibits PAPP-A and PAPP-A2 activity. In collaboration with a group in Madrid, we reported the first human cases carrying mutations in the PAPPA2 gene who presented with short stature, elevated total IGF-1, IGFBP-3, IGFBP-5 and ALS, but low free IGF-1. Additionally, the patients demonstrated insulin resistance and below average bone mineral density (BMD). The PAPP-A2 deficient patients were treated with recombinant human IGF-1, resulting in improvements in growth velocity, insulin resistance, and BMD. These findings suggested that the bioactive, free IGF-1 liberated from IGFBPs by PAPP-A2 is important for human growth. Mouse models of PAPP-A2 and STC2 provide further insights into their roles in growth physiology. This review will summarize new insights into PAPP-A2 and STC2 and their role in the GH-IGF axis, thereby highlighting the importance of the regulation of IGF-1 bioavailability in human health and disease.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.