Activated AMP-protein kinase (pAMPK) is overexpressed in human somatotroph pituitary adenomas.

Autor: Bizzi MF; Departments of Internal Medicine of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Drummond JB; Departments of Internal Medicine of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Pinheiro SVB; Departments of Pediatrics of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Paulino E; Departments of Pathology of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Araújo SA; Departments of Pathology of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Soares BS; Departments of Internal Medicine of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Giannetti AV; Departments of Surgery of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil., Schweizer JROL; Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, LMU Klinikum, 80336, Munich, Germany., Barry S; Centre for Endocrinology of Queen Mary University of London, London, EC1M 6BQ, UK., Korbonits M; Centre for Endocrinology of Queen Mary University of London, London, EC1M 6BQ, UK., Ribeiro-Oliveira A; Departments of Internal Medicine of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 30130-100, Brazil. Electronic address: antoniorojr@gmail.com.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2024 Oct 01; Vol. 592, pp. 112318. Date of Electronic Publication: 2024 Jun 20.
DOI: 10.1016/j.mce.2024.112318
Abstrakt: Introduction: AMPK (AMP-activated protein kinase) is an enzyme that acts as a metabolic sensor and regulates multiple pathways via phosphorylating proteins in metabolic and proliferative pathways. The aim of this work was to study the activated cellular AMPK (phosphorylated-AMPK at Thr172, pAMPK) levels in pituitary tumor samples from patients with sporadic and familial acromegaly, as well as in samples from normal human pituitary gland.
Methods: We studied pituitary adenoma tissue from patients with sporadic somatotroph adenomas, familial acromegaly with heterozygote germline variants in the aryl hydrocarbon receptor interacting protein (AIP) gene (p.Q164*, p.R304* and p.F269_H275dup) and autopsy from normal pituitary glands without structural alterations.
Results: Cellular levels of pAMPK were significantly higher in patients with sporadic acromegaly compared to normal pituitary glands (p < 0.0001). Tissues samples from patients with germline AIP mutations also showed higher cellular levels of pAMPK compared to normal pituitary glands. We did not observe a significant difference in cellular levels of pAMPK according to the cytokeratin (CAM5.2) pattern (sparsely or densely granulated) for tumor samples of sporadic acromegaly.
Conclusion: Our data show, for the first time in human cells, an increase of cellular levels of pAMPK in sporadic somatotropinomas, regardless of cytokeratin pattern, as well as in GH-secreting adenomas from patients with germline AIP mutations.
Competing Interests: Declaration of competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. MFB and AROJr are current full-time employees at Ipsen in Brazil and USA, respectively. AROJr has stock shares from Ipsen.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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