Pegvisomant, a growth hormone-specific antagonist, undergoes cellular internalization

The Journal of Clinical Endocrinology and Metabolism
M MaamraR J M Ross

Abstract

GH binding to a receptor (GHR) dimer triggers signaling and internalization of the receptor/ligand complex. Pegvisomant is a specific GH antagonist developed for the treatment of acromegaly, and the basic molecule is GH with an amino acid substitution that blocks the conformational change necessary to generate functional GHR dimerization required for signal transduction. Pegvisomant has additional polyethylene glycol moieties to prolong its half-life in the circulation and improve clinical efficacy through reduced renal clearance. Pegvisomant has a long plasma half-life, and its mode of clearance has not been established. We have studied pegvisomant internalization and demonstrate that despite its size and prolonged plasma half-life, it is internalized by cells expressing the GHR. As pegvisomant does not activate intracellular signal transduction systems, our results support the concept that the conformational changes required for GHR signaling are not essential for the intracellular trafficking of the ligand and establish one potential contributing mechanism for pegvisomant clearance.

Citations

May 9, 2013·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Juif JenJuliana H Hey-Hadavi
Sep 24, 2014·Journal of Endocrinological Investigation·A GiustinaR Pivonello
Sep 20, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R WebsterD Walker
Jan 18, 2008·Journal of Pharmaceutical Sciences·C Simone Fishburn
May 11, 2013·Endocrinología y nutrición : órgano de la Sociedad Española de Endocrinología y Nutrición·Fernando CordidoUNKNOWN grupo de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición
Oct 13, 2016·Scientific Reports·Ian R WilkinsonRichard J Ross
Jan 3, 2019·The Journal of Clinical Endocrinology and Metabolism·Hainan LanGan Luo
Apr 19, 2011·Orvosi hetilap·Erika HubinaMiklós Góth
Dec 10, 2016·European Journal of Endocrinology·Nicholas A TritosBeverly M K Biller

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society
Le DaoBarbara Lippe
The Journal of Clinical Endocrinology and Metabolism
Aart Jan van der LelyMaria Koltowska-Häggström
© 2021 Meta ULC. All rights reserved