PACAP-38 POSITIVELY REGULATES GLYCOPROTEIN HORMONE ALPHA-GENE EXPRESSION IN PLACENTAL CELLS

The human glycoprotein hormone alpha-gene is transcriptionally activat ed by cAMP in placental cells. We have shown that the novel hypothalam ic peptide, pituitary adenylate cyclase activating polypeptide, PACAP- 38, significantly stimulates intracellular cAMP levels (12-fold increa se; P < 0.001) in JEG-3 choriocarcinoma cells. Regulation of alpha-pro moter activity was assessed using both the chloramphenicol acetyl tran ferase (CAT) and the luciferase (LUC) reporter gene systems. alpha-CAT activity was significantly stimulated by PACAP-38 (4-fold increase; P < 0.05) at 24 h with a similar stimulation being seen with a LUC expr ession vector. The kinetics of stimulation of the alpha-promoter by PA CAP-38 were similar to those seen with 8-Br-cAMP and vasoactive intest inal polypeptide (VIP), a peptide which shares 68% homology with PACAP -38. PACAP-38 also stimulated the production of IL-6 from JEG-3 cells with a time course of response similar to that of alpha-promoter trans cription. We conclude that human placental choriocarcinoma cells posse ss functional receptors for PACAP-38, whose activation enhances cAMP f ormation, alpha-subunit gene transcription and interleukin-6 (IL-6) pr oduction.