A PIT-1 BINDING-SITE IN THE HUMAN RENIN GENE PROMOTER STIMULATES ACTIVITY IN PITUITARY, PLACENTAL AND JUXTAGLOMERULAR CELLS

A Pit-1 binding site in the human renin gene promoter stimulates activ ity in the pituitary, placental and juxtaglomerular cells. One of the principal aims of our research is to determine the mechanisms which di rect renin gene expression to different sites. We recently demonstrate d that human renin (hRen) 5'-flanking DNA sequences -148/+11 can drive the transient expression of a linked luciferase reporter gene transfe cted into pituitary GC cells. This activity was found to be dependent on the binding of Pit-1 to a site approximately 70 bp upstream from th e transcription start site. Pit-1 is a pituitary-specific transcriptio n factor which is involved in directing the cell-specific expression o f growth hormone (GH) and prolactin (PRL) gene expression to somatotro pe and lactotrope cells of the anterior pituitary. Thus, Pit-1 may be play a role in directing the expression of renin to primate lactotrope cells. Renin promoter-driven luciferase or CAT hybrid genes were foun d to be expressed following transfection into primary, or early passag e cell cultures of placental chorionic membranes, and the renin-secret ing renal tumor cell line As4.1. As with GC cells, deletion or mutagen esis of the Pit-1 site reduced activity several-fold in both placental and renal cells. These results suggest that members of the POU family of transcription factors, or some other closely related group such as the Hox proteins, participate in directing renin gene expression to p lacental and juxtaglomerular cells.