title: Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia.
abstract: BACKGROUND
  Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far.
  
  
  METHODS
  We analyzed Melanocortin 2 receptor (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1) expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas from two untreated simple virilizing CAH cases and in two sporadic adrenal myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat numbers in AR exon 1 gene were evaluated in the 4 cases.
  
  
  RESULTS
  The MC2R gene was overexpressed in myelolipomas from 3 out of 4 patients. AR overexpression was detected in 2 tumors: a giant bilateral myelolipoma in a CAH patient and a sporadic case. Simultaneous overexpression of AR and MC2R genes was found in two of the cases. Interestingly, the bilateral giant myelolipoma associated with CAH that had high androgen and ACTH levels but lacked MC2R and AR overexpression presented a significantly shorter AR allele compared with other tumors. In addition, X-chromosome inactivation pattern analysis showed a polyclonal origin in all tumors, suggesting a stimulatory effect as the trigger for tumor development.
  
  
  CONCLUSIONS
  These findings are the first evidence for MC2R or AR overexpression in giant bilateral myelolipomas from poor-compliance CAH patients.
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.forename: Laura C
authors.initials: LC
authors.lastname: Kaupert
authors.forename: Luciana P
authors.initials: LP
authors.lastname: Brito
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Lerario
authors.forename: Beatriz M P
authors.initials: BM
authors.lastname: Mariani
authors.forename: Marta
authors.initials: M
authors.lastname: Ribeiro
authors.forename: Osmar
authors.initials: O
authors.lastname: Monte
authors.forename: Francisco T
authors.initials: FT
authors.lastname: Denes
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.affiliation: Divisão de Endocrinologia e Metabologia, Laboratório de Hormônios e Genética Molecular/LIM42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av, Dr, Enéas de Carvalho Aguiar, 155, 2 andar, Bloco 6, São Paulo, SP 05403-900, Brasil. tbachega@usp.br.
authors.forename: Tânia A S S
authors.initials: TA
authors.lastname: Bachega
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000235:genetics; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications* / Q000235:genetics; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D018209:Myelolipoma / Q000175:diagnosis* / Q000209:etiology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C410798:AR protein, human; D015415:Biomarkers; D012333:RNA, Messenger; D044103:Receptor, Melanocortin, Type 2; D011944:Receptors, Androgen