Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1.
Mol Cell Endocrinol
; 470: 105-114, 2018 07 15.
Article
em En
| MEDLINE
| ID: mdl-28986303
ABSTRACT
BACKGROUND:
Pre-operative detection of corticotropin (ACTH) secreting microadenomas causing Cushing's disease (CD) improves surgical outcomes. Current best magnetic resonance imaging fails to detect up to 40% of these microadenomas. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is specific, but not sensitive in detecting corticotropinomas. Theoretically, secretagogue stimulation with corticotropin releasing hormone (CRH) could improve detection of adenomas with 18F-FDG PET. Previous attempts with simultaneous CRH stimulation have failed to demonstrate increased 18F-FDG uptake in corticotropinomas. We hypothesized that CRH stimulation leads to a delayed elevation in glucose uptake in corticotropinomas.METHODS:
Clinical data was analyzed for efficacy of CRH in improving 18FDG-PET detection of corticotropinomas in CD. Glucose transporter 1 (GLUT1) immunoreactivity was performed on surgical specimens. Ex-vivo, viable cells from these tumors were tested for secretagogue effects (colorimetric glucose uptake), and for fate of intracellular glucose (glycolysis stress analysis). Validation of ex-vivo findings was performed with AtT-20 cells.RESULTS:
CRH increased glucose uptake in human-derived corticotroph tumor cells and AtT-20, but not in normal murine or human corticotrophs (p < 0.0001). Continuous and intermittent (1 h) CRH exposure increased glucose uptake in AtT-20 with maximal effect at 4 h (p = 0.001). Similarly, CRH and 8-Br-cAMP led to robust GLUT1 upregulation and increased membrane translocation at 2 h, while fasentin suppressed baseline (p < 0.0001) and CRH-mediated glucose uptake. Expectedly, intra-operatively collected corticotropinomas demonstrated GLUT1 overexpression. Lastly, human derived corticotroph tumor cells demonstrated increased glycolysis and low glucose oxidation.CONCLUSION:
Increased and delayed CRH-mediated glucose uptake differentially occurs in adenomatous corticotrophs. Delayed secretagogue-stimulated 18F-FDG PET could improve microadenoma detection.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Hormônio Liberador da Corticotropina
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Adenoma Hipofisário Secretor de ACT
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Transportador de Glucose Tipo 1
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Glucose
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Cell Endocrinol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos