FUNCTION OF THE CONSERVED PIT-1 GENE DISTAL ENHANCER IN PROGENITOR AND DIFFERENTIATED PITUITARY-CELLS

Pit-1 is a homeodomain transcription factor that is required for the f unction and survival of the hormone-secreting somatotrope, lactotrope and thyrotrope cells of the anterior pituitary gland. Within the upstr eam region of the mouse Pit-1 gene at around -10 kb, a complex transcr iptional enhancer confers autoregulation and response to hormones and morphogens upon the gene. We demonstrate that this enhancer is conserv ed in both sequence and function and that related sequences are presen t in other rodents. Enhancer sequences from mouse, rat and hamster Pit -1 genes activated transcription from Pit-1 promoter reporter genes in a pituitary progenitor cell line, in somatolactotrope cells and confe rred pituitary cell-specific activation on heterologous promoters. Ele ments allowing regulation by vitamin D-3, pituitary-specific factors a nd Pit-1-dependent response to retinoic acid are well conserved. Studi es comparing distal enhancer activity with that of a second proposed e nhancer sequence at -3 to -5 kb in the rat Pit-1 gene revealed that th e distal enhancer has markedly higher activity than the -3 to -5 kb re gion in both progenitor and differentiated pituitary cell lines. The f unctional conservation of the distal enhancer element suggests that it is critical to the maintenance and cell-specific regulation of Pit-1 gene. Copyright (C) 1996 Elsevier Science Ireland Ltd.