CONTRIBUTION DE L'EXPRESSION ANORMALE DE RECEPTEURS COUPLES AUX PROTEINES G À LA TUMORIGENESE CORTICO-SURRENALIENNE

Abstract : There is evidence for abnormally expression of G protein coupled receptors (GPCR) in adrenocortical tumors. Most of these tumors are benign and associated with cortisol secretion in response to receptor stimulation. However, there was no evidence for a role of GPCRs in adrenal tumorigenesis. To address this question we used an in vivo model of adrenal tumorigenesis in which we expressed the genes for the GIP and LH receptors, both involved in clinical hypercortisolism. We obtained hyperproliferative and hyperfunctional adrenocortical tissues characterized as benign tumors. This is evidence that ectopic expression of a single GPCR gene (GIPR or LHR) can initiate adrenocortical tumorigenesis. Furthermore, we studied a clinical case of catecholamines-responsive Cushing's syndrome secondary to an adrenal hyperplasia. We demonstrated in vitro the β2-adrenoceptor abnormal expression in tumoral cells. Other hormones, such as 5-HT, AVP and ACTH (locally secreted), also mediated the cortisol secretion in this case. In conclusion, a single GPCR expression may induce the development of adrenocortical benign tumors. Some of these tumors migth present miscellaneous genetic abnormalities. Our experimental model will allow studying the multistep tumorigenesis, the expression of other GPCRs and the benefit of new therapeutic strategies in these adrenocortical tumors.
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https://tel.archives-ouvertes.fr/tel-00009050
Contributor : Tânia Mazzuco <>
Submitted on : Monday, April 18, 2005 - 3:17:14 PM
Last modification on : Wednesday, October 16, 2019 - 1:03:22 AM
Long-term archiving on: Friday, April 2, 2010 - 10:03:11 PM

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Tânia Longo Mazzuco. CONTRIBUTION DE L'EXPRESSION ANORMALE DE RECEPTEURS COUPLES AUX PROTEINES G À LA TUMORIGENESE CORTICO-SURRENALIENNE. Sciences du Vivant [q-bio]. Université Joseph-Fourier - Grenoble I, 2005. Français. ⟨tel-00009050⟩

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