Differential gene expression profiles of POMC-related enzymes, transcription factors and receptors between non-pituitary and pituitary ACTH-secreting tumors

Abstract

The differential gene expression of proopiomelanocortin (POMC)-related processing enzymes, transcription factors, and receptors responsible for ACTH secretion between non-pituitary and pituitary ACTH-secreting tumors remains obscure. This study was attempted to determine the gene expression profiles of transcription factors (Tpit, NeuroD1 and IKZF1), proprotein convertase (PC) 1/3 and PC2, and several key receptors linked to ACTH secretion, including corticotrophin releasing hormone receptor (CRHR1), vasopressin receptor 1b (V1bR), somatostatin receptor (SSTR) subtype-2, -5 and dopamine receptor type 2 (D2R) in non-pituitary and pituitary ACTH-secreting tumors. Surgical tissue specimens from carcinoid tumors causing ectopic ACTH syndrome (EAS: n=4) and pituitary tumors causing Cushing's disease (CD: n=13), were subjected to real-time RT-PCR for measurements of each mRNA levels. POMC and CRHR1 mRNA levels in CD were far greater than those in EAS, whereas IKZF1, PC2, SSTR-2 and -5 mRNA levels in EAS were significantly greater than those in CD. NeuroD1, Tpit, PC1/3, V1bR and D2R mRNA levels were comparable between EAS and CD. In conclusion, differential gene expression profiles revealed more abundant mRNA expression in EAS than in CD of 1) IKZF1 with its potential implication of cell differentiation and hormone secretion, 2) PC2 with its possible enhanced processing activity of mature ACTH, and 3) SSTR-2 and -5 with their potential therapeutic application of more selective agonists in EAS patients.