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

Endocrine Journal

Kosuke Mukai¹  Michio Otsuki¹  Toshiharu Onodera¹  Youichi Saitoh³  Toshimitsu Hamasaki⁴  Eiichi Morii⁵  Atsunori Fukuhara¹  Yugo Miyata¹  Satoru Oshino²  Yukiko Tabuchi¹  Tetsuhiro Kitamura¹  Iichiro Shimomura¹ 

[1] Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;Department of Neuromodulation and Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;Office of Biostatistics and Data Management, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan;Department of Pathology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

关键词: Nur77;    Pro-opiomelanocortin;    Adrenocorticotropic hormone;    Cushing’s disease;    Subclinical Cushing’s disease;   

DOI  :  10.1507/endocrj.EJ15-0695

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(20)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.

【 授权许可】

Unknown