Michio Otsuki    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor and Division head
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing's disease and subclinical Cushing's disease
Journal	Formal name：Endocrine Journal Abbreviation：Endocr J ISSN code：09188959
Domestic / Foregin	Domestic
Volume, Issue, Page	63(6),pp.545-554
Author and coauthor	Tabuchi, Y. Kitamura, T. Fukuhara, A. Mukai, K. Onodera, T. Miyata, Y. Hamasaki, T. Oshino, S. Saitoh, Y. Morii, E. Otsuki, M. Shimomura, I.
Authorship	Corresponding author
Publication date	2016
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 alpha: GRalpha). 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.
DOI	10.1507/endocrj.EJ15-0695
Document No.	27025408