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Growth Hormone and Insulin-like Growth Factors
Research Guide
What is Growth Hormone and Insulin-like Growth Factors?
Growth Hormone and Insulin-like Growth Factors refer to growth hormone (GH), a pituitary peptide that stimulates linear growth and metabolism, and the insulin-like growth factors (IGFs), primarily IGF-1 and IGF-2, which mediate many of GH's anabolic effects through endocrine, paracrine, and autocrine actions.
The field encompasses 104,945 published works on GH and IGFs. GH regulates IGF-1 generation, with portal insulin influencing hepatic GH receptor synthesis and IGF-1 production. Key methods include radioiodination of human GH for high specific radioactivity (240-300 μC/μg) as described in 'THE PREPARATION OF 131I-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY' (Greenwood et al., 1963).
Research Sub-Topics
Ghrelin Regulation of Growth Hormone Secretion
Researchers study ghrelin's role as a potent GH-releasing peptide via GHS-R1a receptors in the pituitary and hypothalamus. Investigations cover acylation mechanisms, clinical analogs, and dysregulation in metabolic disorders.
Insulin-like Growth Factor Binding Proteins
This sub-topic examines IGFBPs' modulation of IGF-1/IGF-2 bioavailability, protease regulation, and tissue-specific actions. Studies link IGFBP alterations to cancer progression and metabolic syndrome.
Growth Hormone Receptor Signaling Pathways
Focusing on JAK2-STAT5b pathways, researchers analyze GHR mutations, desensitization, and crosstalk with insulin signaling. Knockout models reveal roles in linear growth and liver metabolism.
IGF-1 Receptor Knockout Models
Studies using Igf1r null mice explore embryonic lethality, metabolic phenotypes, and tissue-specific conditional knockouts. Research connects IGF-1R to longevity, muscle hypertrophy, and neurodegeneration.
Somatostatin Inhibition of Pituitary Growth Hormone
This area investigates hypothalamic somatostatin (SRIF) tone via SSTR subtypes on somatotrophs, including cyclic AMP modulation. Clinical studies target analogs for acromegaly and neuroendocrine tumors.
Why It Matters
Growth Hormone and IGFs impact clinical management of growth disorders and metabolic diseases. FDA approved lonapegsomatropin-tcgd (SKYTROFA®) on July 28, 2025, as a once-weekly prodrug of somatropin for GH replacement in adults with GH deficiency (Ascendis Pharma). Crinetics' once-daily oral treatment for acromegaly achieved 83% patient response in PATHFNDR-1 Phase III trial data presented in 2023. Recent preprints highlight intra-portal insulin's role in GH/IGF-1 axis alterations in acromegaly and disease states, guiding therapy decisions. 'Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions' (Jones and Clemmons, 1995) details IGF biological roles replacing GH sulfation factor activity.
Reading Guide
Where to Start
'Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions' (Jones and Clemmons, 1995) first, as it provides foundational explanation of IGF discovery, actions, and binding proteins replacing GH sulfation factor.
Key Papers Explained
'THE PREPARATION OF 131I-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY' (Greenwood et al., 1963) enabled GH radioimmunoassays, foundational for later works like 'Ghrelin is a growth-hormone-releasing acylated peptide from stomach' (Kojima et al., 1999) identifying stomach-derived GH regulators and 'Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions' (Jones and Clemmons, 1995) detailing IGF mediation of GH effects. 'Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone' (Brazeau et al., 1973) complements by showing GH inhibition mechanisms. 'Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)' (Liu et al., 1993) builds genetically validating these pathways.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Preprints emphasize intra-portal insulin's regulation of GH/IGF-1 axis in health, disease, and acromegaly therapy ('Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin', 2025-09-04). FDA approvals like lonapegsomatropin-tcgd for GH deficiency (2025-07-28) and Crinetics' paltusotine for acromegaly (2025-09-25, 83% response) drive biomarker refinement ('Growth Hormone Research Society perspective on biomarkers of GH action in children and adults', 2025-09-19).
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | THE PREPARATION OF 131I-LABELLED HUMAN GROWTH HORMONE OF HIGH ... | 1963 | Biochemical Journal | 10.2K | ✓ |
| 2 | Ghrelin is a growth-hormone-releasing acylated peptide from st... | 1999 | Nature | 8.4K | ✕ |
| 3 | Preparation of Iodine-131 Labelled Human Growth Hormone of Hig... | 1962 | Nature | 7.0K | ✕ |
| 4 | Establishment of a noradrenergic clonal line of rat adrenal ph... | 1976 | Proceedings of the Nat... | 5.6K | ✓ |
| 5 | Classification criteria for Sjögren's syndrome: a revised vers... | 2002 | Annals of the Rheumati... | 5.3K | ✓ |
| 6 | Insulin-Like Growth Factors and Their Binding Proteins: Biolog... | 1995 | Endocrine Reviews | 4.5K | ✕ |
| 7 | Serum TSH, T<sub>4</sub>, and Thyroid Antibodies in the United... | 2002 | The Journal of Clinica... | 3.8K | ✕ |
| 8 | Hypothalamic Polypeptide That Inhibits the Secretion of Immuno... | 1973 | Science | 3.5K | ✕ |
| 9 | The Transforming Growth Factor-beta Family | 1990 | Annual Review of Cell ... | 3.0K | ✕ |
| 10 | Mice carrying null mutations of the genes encoding insulin-lik... | 1993 | Cell | 2.9K | ✕ |
In the News
FDA Approves SKYTROFA® (Lonapegsomatropin-tcgd) for ...
Ascendis Pharmais a global biopharmaceutical company focused on applying our innovative TransCon technology platform to make a meaningful difference for patients. Guided by our core values of Patie...
Peptide Hubs Elevates Global Research Standards with ...
**2. GHRP-6 Peptide: Unlocking Growth Hormone Mechanisms**
FDA Approves Crinetics' Once-Daily Acromegaly Treatment
Crinetics filed the new drug application back in December 2024 backed by data from two Phase III trials—PATHFNDR-1 and PATHFNDR-2. In the first trial, data presented in 2023 showed 83% of patients ...
Lonapegsomatropin-tcgd Receives FDA Approval for ...
The FDA has approved lonapegsomatropin-tcgd (Skyrofa; Ascendis Pharma), a prodrug of somatropin, a human growth hormone administered once weekly for the replacement of endogenous growth hormone in ...
Chemistry Alum's Company Wins FDA Approval for First Oral ...
the level of another hormone called IGF-1, or insulin-like growth factor 1.
Code & Tools
A Ruby gem for calculating anthropometric z-scores and percentiles based on the WHO and CDC 2000 growth chart data. ### License MIT license
The goal of this project is to build a closed-loop AP (artificial pancreas) controller to automatically manage diabetes treatment. The controller s...
Pharmpy is an open-source software package for pharmacometric modeling. It has functionality ranging from reading and manipulating model files and ...
This repository contains a closed-loop testbed for the artificial pancreas system (APS) that evaluates the effectiveness of new control algorithms ...
# iglu: Interpreting data from Continuous Glucose Monitors (CGMs) The R package ‘iglu’ provides functions for outputting relevant metrics for dat...
Recent Preprints
Endocrinology and Metabolism
* Current Knowledge on Atypical Parathyroid Tumors and Emerging Strategies for Risk Stratification VIEW MORE MOST CITED * The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Fa...
current understanding of how changes in intra-portal insulin delivery to the liver in health, disease states and drug therapy use and misuse that leads to alterations in GH/IGF-I secretion that may...
Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin
Growth hormone (GH) is the key regulator of insulin-like growth factor I (IGF-I) generation in healthy states. However, portal insulin delivery is also an essential co-player in the regulation of t...
Metabolic factors influencing the efficacy of recombinant human growth hormone therapy in children with short stature
studies exploring factors influencing rhGH efficacy have focused on baseline height, age, skeletal age (SA), body mass index (BMI), insulin-like growth factor-1 (IGF1), growth hormone stimulation t...
Growth Hormone Research Society perspective on biomarkers of GH action in children and adults
recognized (2, 5). The obvious biomarkers of growth hormone (GH) action in children and adults are serum levels of GH itself and of insulin-like growth factor-I (IGF-I). Both are used diagnostic...
Latest Developments
Recent developments in Growth Hormone and Insulin-like Growth Factors research include ongoing exploration of their regulation and roles in health and disease, with notable advances such as the publication of a review on growth hormone-releasing hormone analogues in November 2024 (Nature Reviews Endocrinology) and a study on the growth hormone/IGF-I axis in relation to intra-portal insulin published in November 2024 (Frontiers in Endocrinology). Additionally, research continues into the actions of IGF-1 in the brain and neuropsychiatric diseases, with a study from July 2025 highlighting its significance (PMC).
Sources
Frequently Asked Questions
What is the method for preparing high specific radioactivity 131I-labelled human growth hormone?
A simple method uses 2 mC carrier-free 131I iodide reacting with 5 μg human GH to yield 240-300 μC/μg specific radioactivity. Described in 'THE PREPARATION OF 131I-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY' (Greenwood et al., 1963). This enables precise radioimmunoassays for GH measurement.
How does ghrelin relate to growth hormone?
Ghrelin is a growth-hormone-releasing acylated peptide from the stomach. 'Ghrelin is a growth-hormone-releasing acylated peptide from stomach' (Kojima et al., 1999) identified it as a potent GH secretagogue.
What are the biological actions of insulin-like growth factors?
IGFs stimulate cartilage sulfation, replacing GH sulfation factor activity in vitro. They act via endocrine, paracrine, and autocrine mechanisms with binding proteins modulating effects. Detailed in 'Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions' (Jones and Clemmons, 1995).
What inhibits pituitary growth hormone secretion?
A hypothalamic peptide with sequence H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH inhibits immunoreactive GH at 1 × 10^-9 M in vitro and in vivo. Reported in 'Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone' (Brazeau et al., 1973).
What phenotypes result from Igf-1 and Igf1r null mutations in mice?
Mice with null mutations in Igf-1 and type 1 IGF receptor (Igf1r) genes show severe growth deficiency. 'Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)' (Liu et al., 1993) established these models demonstrating IGF-1 essentiality for postnatal growth.
What biomarkers indicate GH action?
Serum GH and IGF-1 levels serve as primary biomarkers for GH action in children and adults. 'Growth Hormone Research Society perspective on biomarkers of GH action in children and adults' (2025) notes their diagnostic and monitoring roles in GH deficiency.
Open Research Questions
- ? How does intra-portal insulin delivery quantitatively alter hepatic GH sensitivity and IGF-1 generation in acromegaly?
- ? What basal metabolic factors, beyond BMI and IGF-1, predict recombinant human GH therapy efficacy in short stature children?
- ? Which serum IGF-1 thresholds optimize monitoring during GH replacement in adults?
- ? How do portal insulin changes in disease states dictate GH/IGF-1 axis management?
- ? What distinguishes atypical parathyroid tumors' GH/IGF interactions from standard endocrine regulation?
Recent Trends
FDA approvals advanced GH therapy: lonapegsomatropin-tcgd (SKYTROFA®) for adult GH deficiency and Crinetics' oral paltusomatropin for acromegaly with 83% response in PATHFNDR-1 (2025-09-25).
2025-07-28Preprints focus on intra-portal insulin regulating GH/IGF-1 axis in acromegaly and metabolic influences on rhGH efficacy in short stature ('Metabolic factors influencing the efficacy of recombinant human growth hormone therapy in children with short stature', 2025-11-03).
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