title: Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing's disease and subclinical Cushing's disease.
abstract: Cushing's disease (CD) and subclinical Cushing's disease (subCD) are both diseases caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. However, ACTH autonomy in subCD is weaker than in CD and there are no Cushingoid features in subCD. The differences of molecular mechanisms in ACTH autonomy between CD and subCD have not yet been reported. Therefore, we aimed to investigate the differences in molecular mechanisms of ACTH-secretion autonomy between CD and subCD. The study included 23 patients [7 CD, 6 subCD, and 10 non-functioning pituitary tumors (NFTs)] who underwent transsphenoidal surgery at the Osaka University Hospital between December 2009 and October 2013. Using quantitative real-time PCR, various ACTH-related gene expressions in tumor tissues from CD, subCD, and NFT were measured such as pro-opiomelanocortin (POMC), POMC transcription factor (Tpit, Pitx1, NeuroD1, and Nur77), POMC peptide processing enzymes (prohormone convertase: PC1/3 and PC2), and ACTH secretion-related factors (corticotropin-releasing hormone receptor 1: CRHR1 and glucocorticoid receptor α: GRα). Only Nur77 mRNA levels were significantly higher in CD than in subCD. Furthermore, we stained 6 CD and 6 subCD with anti-Nur77 antibody. All tumor samples from CD had Nur77 protein positive cells. On the other hand, Nur77 protein was expressed in only one tumor sample from subCD. This sample showed high expression of Nur77 mRNA. Nur77 is an important to regulate POMC transcription and negative-feedback by glucocorticoids. Nur77 gene expression levels might involve different autonomy of ACTH production between CD and subCD.
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Atsunori
authors.initials: A
authors.lastname: Fukuhara
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mukai
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Onodera
authors.forename: Yugo
authors.initials: Y
authors.lastname: Miyata
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Oshino
authors.forename: Youichi
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.forename: Michio
authors.initials: M
authors.lastname: Otsuki
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D016022:Case-Control Studies; D025461:Feedback, Physiological; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics*; D047748:Pituitary ACTH Hypersecretion / Q000235:genetics* / Q000378:metabolism; D055571:Secretory Pathway / Q000235:genetics; D055815:Young Adult
chemical_list: C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D000324:Adrenocorticotropic Hormone