Insulin-Like Growth Factor Pathway and the Thyroid.
Acromegaly
/ metabolism
Animals
Antibodies, Monoclonal, Humanized
/ pharmacology
Autoantibodies
/ chemistry
Binding Sites
Clinical Trials as Topic
Graves Disease
/ metabolism
Graves Ophthalmopathy
/ drug therapy
Growth Hormone
/ metabolism
Humans
Insulin-Like Growth Factor Binding Proteins
/ metabolism
Insulin-Like Growth Factor I
/ metabolism
Insulin-Like Growth Factor II
/ metabolism
Ligands
Pyroptosis
Receptor, IGF Type 1
/ metabolism
Receptors, Thyrotropin
/ immunology
Signal Transduction
Thyroid Gland
/ metabolism
Thyrotropin
/ metabolism
Graves’ disease
autoimmune
goiter
growth factor
hormone
ophthalmopathy
thyroid
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2021
2021
Historique:
received:
14
01
2021
accepted:
20
04
2021
entrez:
21
6
2021
pubmed:
22
6
2021
medline:
22
12
2021
Statut:
epublish
Résumé
The insulin-like growth factor (IGF) pathway comprises two activating ligands (IGF-I and IGF-II), two cell-surface receptors (IGF-IR and IGF-IIR), six IGF binding proteins (IGFBP) and nine IGFBP related proteins. IGF-I and the IGF-IR share substantial structural and functional similarities to those of insulin and its receptor. IGF-I plays important regulatory roles in the development, growth, and function of many human tissues. Its pathway intersects with those mediating the actions of many cytokines, growth factors and hormones. Among these, IGFs impact the thyroid and the hormones that it generates. Further, thyroid hormones and thyrotropin (TSH) can influence the biological effects of growth hormone and IGF-I on target tissues. The consequences of this two-way interplay can be far-reaching on many metabolic and immunologic processes. Specifically, IGF-I supports normal function, volume and hormone synthesis of the thyroid gland. Some of these effects are mediated through enhancement of sensitivity to the actions of TSH while others may be independent of pituitary function. IGF-I also participates in pathological conditions of the thyroid, including benign enlargement and tumorigenesis, such as those occurring in acromegaly. With regard to Graves' disease (GD) and the periocular process frequently associated with it, namely thyroid-associated ophthalmopathy (TAO), IGF-IR has been found overexpressed in orbital connective tissues, T and B cells in GD and TAO. Autoantibodies of the IgG class are generated in patients with GD that bind to IGF-IR and initiate the signaling from the TSHR/IGF-IR physical and functional protein complex. Further, inhibition of IGF-IR with monoclonal antibody inhibitors can attenuate signaling from either TSHR or IGF-IR. Based on those findings, the development of teprotumumab, a β-arrestin biased agonist as a therapeutic has resulted in the first medication approved by the US FDA for the treatment of TAO. Teprotumumab is now in wide clinical use in North America.
Identifiants
pubmed: 34149612
doi: 10.3389/fendo.2021.653627
pmc: PMC8212127
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Autoantibodies
0
Insulin-Like Growth Factor Binding Proteins
0
Ligands
0
Receptors, Thyrotropin
0
Insulin-Like Growth Factor I
67763-96-6
Insulin-Like Growth Factor II
67763-97-7
Thyrotropin
9002-71-5
Growth Hormone
9002-72-6
Receptor, IGF Type 1
EC 2.7.10.1
teprotumumab
Y64GQ0KC0A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
653627Informations de copyright
Copyright © 2021 Smith.
Déclaration de conflit d'intérêts
The author declares US Patents covering the use of IGF-1 receptor inhibitors in autoimmune disease and consultancy for Horizon Therapeutics Consultant Immunovant.
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