title: Steroid-dependent ACTH-produced thymic carcinoid: regulation of POMC gene expression by cortisol via methylation of its promoter region.
abstract: OBJECTIVE
  Metyrapone causes a decrease in the serum cortisol level without affecting ACTH production in ectopic tumors. We report a case who presented with Cushing's syndrome due to an ectopic ACTH-producing thymic carcinoid. In the present case, it was demonstrated that metyrapone administration resulted in a significant decrease in the plasma ACTH and serum cortisol levels. We hypothesized that the steroid hormone may promote proopiomelanocortin (POMC) gene expression in the carcinoid cells.
  
  
  METHODS
  An 11-year-old boy presented with Cushing's syndrome. Prior to the detection of a thymic tumor, metyrapone was administered to ameliorate the symptoms of Cushing's syndrome. Interestingly, plasma ACTH as well as serum cortisol levels immediately decreased after metyrapone administration. The levels of cortisol and ACTH were observed to be normal after complete surgical resection of the tumor. Biological characterization of the tumor cells was by in vitro analysis.
  
  
  RESULTS
  Thein vitro culture of the tumor cells showed an increased expression of POMC in the presence of cortisol. A CpG methylation assay showed that the demethylation of the POMC promoter was induced by a steroid hormone.
  
  
  CONCLUSIONS
  These findings suggest that the ectopic ACTH-producing tumor may partly be regulated by the elevated levels of cortisol.
authors.affiliation: Department of Pediatrics, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizoguchi
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Kajiume
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okada
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishi
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000963:Antimetabolites / Q000627:therapeutic use; D002276:Carcinoid Tumor / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D002648:Child; D019175:DNA Methylation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008797:Metyrapone / Q000627:therapeutic use; D008954:Models, Biological; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011859:Radiography; D013953:Thymus Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000963:Antimetabolites; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008797:Metyrapone