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

Autor(es)

Soares Costa, Marcia Helena ^{[1, 2]} ; Domenice, Sorahia ^[1] ; Toledo, Rodrigo Almeida ^[3] ; Junior, Delmar Muniz L. ^[3] ; Latronico, Ana Claudia ^{[1, 2]} ; Pinto, Emilia Modolo ^[4] ; Almeida Toledo, Sergio Pereira ^[3] ; Mendonca, Berenice Bilharinho ^[1] ; Barisson Villares Fragoso, Maria Candida ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM 42, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Unidade Suprarrenal, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Unidade Endocrinol Genet LIM 25, BR-05508 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Lab Patol Med LIM 22, Disciplina Endocrinol Metabol, Hosp Clin, Fac Med, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 66, n. 4, p. 529-533, 2011.
• Citações Web of Science: 6

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 Delta Delta CT method, and beta-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. (AU)

• Processo FAPESP: 03/07449-1 - Estudo da expressão de receptores anômalos em tumores adrenocorticais e em tecidos adrenais de pacientes com hiperplasia macronodular primária independente de ACTH (AIMAH) e neoplasia endócrina múltipla
• Beneficiário: Marcia Helena Soares Costa
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 04/15046-7 - Estudo da expressão de receptores anômalos em tumores adrenocorticais e em tecidos adrenais de pacientes com hiperplasia macronodular primária independente de ACTH (AIMAH) e neoplasia endócrina múltipla
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Regular