Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing’s disease and subclinical Cushing’s disease

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...

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Bibliographic Details
Published in:Endocrine Journal 2016, Vol.63(6), pp.545-554
Main Authors: Tabuchi, Yukiko, Kitamura, Tetsuhiro, Fukuhara, Atsunori, Mukai, Kosuke, Onodera, Toshiharu, Miyata, Yugo, Hamasaki, Toshimitsu, Oshino, Satoru, Saitoh, Youichi, Morii, Eiichi, Otsuki, Michio, Shimomura, Iichiro
Format: Article
Language:English
Subjects:
ACTH-Secreting Pituitary Adenoma - genetics
ACTH-Secreting Pituitary Adenoma - secretion
Adenoma - genetics
Adenoma - secretion
Adrenocorticotropic hormone
Adrenocorticotropic Hormone - secretion
Adult
Aged
Asymptomatic Diseases
Case-Control Studies
Cushing’s disease
Feedback, Physiological
Female
Gene Expression
Humans
Male
Middle Aged
Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
Nur77
Pituitary ACTH Hypersecretion - genetics
Pituitary ACTH Hypersecretion - metabolism
Pro-opiomelanocortin
Secretory Pathway - genetics
Subclinical Cushing’s disease
Young Adult
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Summary: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.
ISSN:0918-8959
1348-4540
DOI:10.1507/endocrj.EJ15-0695