Could calgranulins and advanced glycated end products potentiate acromegaly pathophysiology?

Abstract

Growth hormone (GH) exerts a diverse set of effects across many tissues including fat, muscle, bone, kidney, heart, and liver. GH is also a diabetogenic hormone in that it inhibits the actions of insulin. Acromegaly, a condition traditionally characterized by increased levels of growth hormone secretion as a result of pituitary adenoma, results in increased tissue growth, lipolysis, and can result in patients with hyperglycemia and hyperinsulinemia. While current treatment modalities have greatly improved prognoses for most patients, a significant number present clinical symptoms of acromegaly with elevated levels of IGF-1 in the absence of increased GH levels, a phenomenon known as micromegaly. This condition presents a challenge to most currently used treatments since the high circulating IGF-1 levels are independent of elevated levels of GH. It has been previously shown that advanced glycation end products (AGE) can stimulate IGF-1 secretion by human monocytes in vitro, demonstrating a possible mechanism for increased IGF-1 levels. To further investigate AGE/GH/IGF-1 interaction, we have reanalyzed a publicly available RNAseq dataset from subcutaneous adipose tissue of patients with acromegaly. S100A1, a member of the calgranulin family of proteins and ligand of the AGE receptor, was shown to be significantly upregulated in patients with acromegaly. These findings identify an important consideration that may help explain the counterintuitive nature of micromegaly, while simultaneously providing new insight into the role of GH in diabetic, inflammatory, and immune pathologies.

• Authors: Colin P S Kruse, David A Cottrill, John J Kopchick
• Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society (Growth Horm IGF Res) 2019 Jun - Aug Vol. 46-47 Pg. 1-4 ISSN: 1532-2238 [Electronic] Scotland
• PMID: 31071497 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Glycation End Products, Advanced
• IGF1 protein, human
• S100 Proteins
• S100A1 protein
• Human Growth Hormone
• Insulin-Like Growth Factor I

Topics

• Acromegaly (physiopathology)
• Adipose Tissue, White (physiopathology)
• Gene Regulatory Networks
• Glycation End Products, Advanced (metabolism)
• Human Growth Hormone (metabolism)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Pituitary Neoplasms (physiopathology)
• S100 Proteins (metabolism)
• Subcutaneous Tissue (physiopathology)