The human POMC promoter: where do we stand?

Proopiomelanocortin (POMC) is crucial for several life-essential functions and its regulation has been studied extensively in the past decades. The first studies provided the framework for POMC promoter activity, namely the identification for the major response elements contained in the promoter, e.g., the glucocorticoid response element, the Nur response element, while subsequent studies showed the importance of cooperation and interplay between transcription factors to achieve optimal promoter activity. The involvement of constitutive repressors of POMC transcription, such as Bmp4, provided the latest clues to our understanding of POMC promoter activity. This increased knowledge benefits the clinician as it allows genetic testing and early recognition of patients with congenital ACTH deficiency due to mutations in TPIT and paves the way to new medical treatments in Cushing's disease. The present review will illustrate the current standing on regulation of the human POMC promoter, focusing on its activity in corticotropes.