Novel elements in the uteroglobin promoter are a functional target for prolactin signaling.

To quantify uteroglobin (UG) gene expression, varying lengths of 5' flanking sequence were subcloned into a luciferase reporter plasmid and introduced into HRE-H9 uterine epithelial cells. In response to estrogen, prolactin (PRL) and progesterone, transcriptional activity was maximal for the full-length construct, pUG3.1-LUC. Transcriptional activity was reduced (P < 0.05) by the removal of the progesterone receptor binding site, tested with pUG2.3-LUC, and eliminated (P < 0.05) by the removal of the remaining 5' flanking sequences, tested with pUG0.1-LUC. When the effects of PRL +/- progesterone were evaluated, progesterone alone increased (P < 0.05) the transcriptional activity of pUG3.1-LUC, and the deletion mutant, pUG3.1deltaRUSH-LUC. Transcription of pUG3.1-LUC was further increased (P < 0.05) by PRL + progesterone. However, deletion of the proximal promoter region -170/-85, tested with pUG3.1deltaRUSH-LUC, eliminated (P > 0.05) the PRL effect. These data support the speculation that RUSH proteins which bind to this region of the promoter play an important regulatory role in PRL signal transduction.