ECE2008 Poster Presentations Endocrine tumours (77 abstracts)
Ghrelin and its receptor are present in an ectopic ACTH lung neuroendocrine tumour causing Cushing's syndrome: potential pathophysiological implications
Ana Quintero 1 , Antonio J Martínez-Fuentes 1 , Manuel D Gahete 1 , Rafael Vázquez-Martínez 1 , Carmen Gutiérrez-Alcantara 2 , Luis Jiménez-Reina 3 , Pedro Benito-López 2 , María M Malagón 1 & Justo P Castaño 1
1Department of Cell Biology, Physiology and Immunology, Instituto de Salud Carlos III, University of Córdoba and CIBER Fisiopatologia Obesidad y Nutricion (CB06/03), Cordoba, Spain; 2Department of Endocrinology and Nutrition, Reina Sofia Hospital, Cordoba, Spain; 3Department of Morphological Sciences, University of Cordoba, Corrdoba, Spain.
Ghrelin is a 28-aa peptide originally isolated from stomach but present also in many tissues, including hypothalamus and pituitary, where it stimulates growth hormone (GH) release through the ghrelin/GH secretagogue receptor (GHS-R). Ghrelin also increases food intake and adiposity and could play a key integrative role in the endocrine–metabolic interface. Although its primary pituitary cell target are somatotropes, ghrelin also modulates other pituitary cell types, specially in certain pathologies. Indeed, we recently showed that human pituitary adenomas causing Cushing’s disease express both ghrelin and GHS-R. Moreover, ghrelin was co-stored within ACTH secretory granules, and increased free cytosolic calcium ([Ca2+]i) and presumably ACTH release via GHS-R. These results provided a cellular basis for the exaggerated ACTH response to ghrelin in Cushing’s disease and suggested an association of the ghrelin/GHS-R system with the pathophysiology of corticotropinomas. Because Cushing’s syndrome is frequently caused by ectopic ACTH secretion from non-pituitary neuroendocrine tumours, specially lung carcinoids, we explored the possible presence of ghrelin/GHS-R system in these tumours. Specifically, a 70-year-old woman was diagnosed of a lung carcinoid tumour with ectopic ACTH secretion. Freshly isolated tumour lung pieces were processed for: (a) immunomicroscopy; (b) measurement of ghrelin-induced changes in [Ca2+]i and secretory activity in single living cells; and (c) RT-PCR expression analysis. As expected, 97% cells from the ectopic lung carcinoid tumour showed ACTH immunofluorescence. RT-PCR confirmed ACTH (POMC) expression and further revealed that the lung carcinoid tissue also express ghrelin and GHS-R1a. Moreover, ghrelin (1 μM) stimulated [Ca2+]i in 80% of cells (n=20), and increased the rate of incorporation of the fluorescent dye FM-5-95, suggesting increased hormone release. Taken together, our results demonstrate that, as in pituitary corticotropinomas, ghrelin and GHS-R1a are functionally present in an ectopic corticotropinoma causing Cushing’s syndrome, and could therefore provide an autocrine mechanisms involved in the pathophysiology of these tumours.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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