Promoter activity of human renin 5'-flanking DNA sequences is activated by the pituitary-specific transcription factor Pit-1

Although the renal juxtaglomerular cell is the source of circulating renin, the renin gene is also expressed at a number of extrarenal sites including lactotrope cells of human and ovine pituitaries. In the present study, we demonstrate that GC cells, a pituitary lactotrope precursor cell line, efficiently express transiently transfected hybrid genes containing human renin 5'-flanking DNA sequences -148/+11. Gel mobility shift competition analyses show that a highly conserved sequence in human and rodent renin 5'-flanking DNAs (human coordinates: -80/-58) binds a nuclear factor from GC cells, most likely the pituitary-specific factor Pit-1. Deletional and mutational analyses demonstrate that this site is a major determinant of renin promoter activity in GC cells. Transfection of a Pit-1 expression construct into HeLa cells, where activity of the human renin promoter is low, stimulates expression of cotransfected renin-luciferase constructs. Moreover, activation of the human renin promoter by co-expression of Pit-1 is dependent on an intact Pit-1 site. Taken together, these data strongly suggest that Pit-1 activates pituitary renin gene expression. This finding raises the possibility that member(s) of the POU family of transcription factors, of which Pit-1 is an archetypal member, may direct renin expression in other tissues, including the kidney.