Pituitary-Specific Factor Binding to the Human Prolactin,Growth Hormone,and Placental Lactogen Genes

The human genes coding for growth hormone (GH), chorionic somatomammotropin (placental lactogen, CS), and prolactin (Prl) are related evolutionarily but are expressed in phenotypically distinct cell types despite their nucleotide sequence homology. We show here that the promoters of the human Prl and CS genes contain cis-acting sequences that confer pituitary-specific expression in a cell-free transcription assay. Similar data are obtained with the human GH gene, consistent with earlier work by others. Footprinting analysis shows that neighboring sequences in each of these three promoters are protected from deoxyribonuclease I digestion by rat pituitary cell extracts. Footprinting competition experiments and gel retardation assays with synthetic oligonucleotides suggest that a single factor is responsible for the pituitary-specific footprints seen on the human Prl, CS, and GH genes. They also suggest that this factor is identical or closely related to the trans-acting factor GHF-1/Pit-1. Similarities with and differences from the rat GH and Prl genes are discussed.