PITUITARY-SPECIFIC REPRESSION OF PLACENTAL MEMBERS OF THE HUMAN GROWTH-HORMONE GENE FAMILY - A POSSIBLE MECHANISM FOR LOCUS REGULATION

Five members of the human growth hormone (GH) gene family are located at a single locus on chromosome 17. Growth hormone is expressed in the pituitary under the control of the tissue-specific factor Pit 1/GHF-1 , and chorionic somatomammotropin (CS) -A, -B, and -L, as well as plac ental GH variant, are expressed specifically in the placental syncytio trophoblast. Despite this specificity in vivo, the CS-A promoter can b ind Pit 1/GHF-1 and allow CS-A promoter activity in pituitary tumor ce lls after gene transfer. We have identified and characterized PSF sequ ences associated with only the placental members in the GH/CS locus wh ich repress placental promoter activity >90% in transfected pituitary cells. These sequences do not significantly affect promoter function i n placental cells after gene transfer. Repressor activity correlates w ith binding of protein at two sites (PSF-A and PSF-B) with pituitary, but not placental, nuclear extracts. Competition studies suggest an in teraction between PSF and Pit 1/GHF-1 proteins. These results indicate that PSF protein can repress CS-A promoter activity in a tissue-speci fic manner in vitro and provide a possible mechanism by which expressi on of placental members of the GH family are inhibited in the pituitar y in vivo.