TY - JOUR
T1 - Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing’s disease and subclinical Cushing’s disease
AU - Tabuchi, Yukiko
AU - Kitamura, Tetsuhiro
AU - Fukuhara, Atsunori
AU - Mukai, Kosuke
AU - Onodera, Toshiharu
AU - Miyata, Yugo
AU - Otsuki, Michio
AU - Shimomura, Iichiro
AU - Hamasaki, Toshimitsu
AU - Oshino, Satoru
AU - Saitoh, Youichi
AU - Morii, Eiichi
N1 - Publisher Copyright:
© The Japan Endocrine Society.
PY - 2016
Y1 - 2016
N2 - 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 ACTHsecretion 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 secretionrelated 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.
AB - 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 ACTHsecretion 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 secretionrelated 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.
KW - Adrenocorticotropic hormone
KW - Cushing’s disease
KW - Nur77
KW - Pro-opiomelanocortin
KW - Subclinical Cushing’s disease
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U2 - 10.1507/endocrj.EJ15-0695
DO - 10.1507/endocrj.EJ15-0695
M3 - Article
C2 - 27025408
AN - SCOPUS:84976498689
SN - 0918-8959
VL - 63
SP - 545
EP - 554
JO - Endocrine Journal
JF - Endocrine Journal
IS - 6
ER -