Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus

Detalhes bibliográficos
Autor(a) principal: Costa, Marcia Helena Soares
Data de Publicação: 2011
Outros Autores: Domenice, Sorahia, Toledo, Rodrigo Almeida, L. Junior, Delmar Muniz, Latronico, Ana Claudia, Pinto, Emilia Modolo, Toledo, Sergio Pereira Almeida, Mendonca, Berenice Bilharinho, Fragoso, Maria Candida Barisson Villares
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Clinics
Texto Completo: https://www.revistas.usp.br/clinics/article/view/19580
Resumo: BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical hyperplasia. New prospective studies will be able to clarify the exact role of the glucose-dependent insulinotropic peptide receptor in the molecular pathogenesis of MEN1 adrenocortical lesions.
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spelling Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus MEN1adrenocortical hyperplasiaGIPRexpression BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical hyperplasia. New prospective studies will be able to clarify the exact role of the glucose-dependent insulinotropic peptide receptor in the molecular pathogenesis of MEN1 adrenocortical lesions. Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2011-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/1958010.1590/S1807-59322011000400002Clinics; Vol. 66 No. 4 (2011); 529-533 Clinics; v. 66 n. 4 (2011); 529-533 Clinics; Vol. 66 Núm. 4 (2011); 529-533 1980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/19580/21643Costa, Marcia Helena SoaresDomenice, SorahiaToledo, Rodrigo AlmeidaL. Junior, Delmar MunizLatronico, Ana ClaudiaPinto, Emilia ModoloToledo, Sergio Pereira AlmeidaMendonca, Berenice BilharinhoFragoso, Maria Candida Barisson Villaresinfo:eu-repo/semantics/openAccess2012-05-23T16:49:43Zoai:revistas.usp.br:article/19580Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2012-05-23T16:49:43Clinics - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
title Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
spellingShingle Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
Costa, Marcia Helena Soares
MEN1
adrenocortical hyperplasia
GIPR
expression
title_short Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
title_full Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
title_fullStr Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
title_full_unstemmed Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
title_sort Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus
author Costa, Marcia Helena Soares
author_facet Costa, Marcia Helena Soares
Domenice, Sorahia
Toledo, Rodrigo Almeida
L. Junior, Delmar Muniz
Latronico, Ana Claudia
Pinto, Emilia Modolo
Toledo, Sergio Pereira Almeida
Mendonca, Berenice Bilharinho
Fragoso, Maria Candida Barisson Villares
author_role author
author2 Domenice, Sorahia
Toledo, Rodrigo Almeida
L. Junior, Delmar Muniz
Latronico, Ana Claudia
Pinto, Emilia Modolo
Toledo, Sergio Pereira Almeida
Mendonca, Berenice Bilharinho
Fragoso, Maria Candida Barisson Villares
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Costa, Marcia Helena Soares
Domenice, Sorahia
Toledo, Rodrigo Almeida
L. Junior, Delmar Muniz
Latronico, Ana Claudia
Pinto, Emilia Modolo
Toledo, Sergio Pereira Almeida
Mendonca, Berenice Bilharinho
Fragoso, Maria Candida Barisson Villares
dc.subject.por.fl_str_mv MEN1
adrenocortical hyperplasia
GIPR
expression
topic MEN1
adrenocortical hyperplasia
GIPR
expression
description BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1) remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity) had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8) higher than the normal adrenal controls (p = 0.02). CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of adrenocortical hyperplasia. New prospective studies will be able to clarify the exact role of the glucose-dependent insulinotropic peptide receptor in the molecular pathogenesis of MEN1 adrenocortical lesions.
publishDate 2011
dc.date.none.fl_str_mv 2011-01-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/clinics/article/view/19580
10.1590/S1807-59322011000400002
url https://www.revistas.usp.br/clinics/article/view/19580
identifier_str_mv 10.1590/S1807-59322011000400002
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/clinics/article/view/19580/21643
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
publisher.none.fl_str_mv Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo
dc.source.none.fl_str_mv Clinics; Vol. 66 No. 4 (2011); 529-533
Clinics; v. 66 n. 4 (2011); 529-533
Clinics; Vol. 66 Núm. 4 (2011); 529-533
1980-5322
1807-5932
reponame:Clinics
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Clinics
collection Clinics
repository.name.fl_str_mv Clinics - Universidade de São Paulo (USP)
repository.mail.fl_str_mv ||clinics@hc.fm.usp.br
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