title: Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unidade de Suprarrenal, do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, SP, Brasil. mhsc@usp.br
authors.forename: Marcia Helena Soares
authors.initials: MH
authors.lastname: Costa
authors.forename: Sorahia
authors.initials: S
authors.lastname: Domenice
authors.forename: Rodrigo Almeida
authors.initials: RA
authors.lastname: Toledo
authors.forename: Delmar Muniz
authors.initials: DM
authors.lastname: Lourenço
authors.forename: Delmar Muniz Junior
authors.initials: DM
authors.lastname: Lourenço
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.forename: Emilia Modolo
authors.initials: EM
authors.lastname: Pinto
authors.forename: Sergio Pereira Almeida
authors.initials: SP
authors.lastname: Toledo
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Maria Candida Barisson Villares
authors.initials: MC
authors.lastname: Fragoso
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor