PACAP-38 positively regulates glycoprotein hormone alpha-gene expression in placental cells.
The human glycoprotein hormone alpha-gene is transcriptionally activated by cAMP in placental cells. We have shown that the novel hypothalamic peptide, pituitary adenylate cyclase activating polypeptide, PACAP-38, significantly stimulates intracellular cAMP levels (12-fold increase; P < 0.001) in JEG-3 choriocarcinoma cells. Regulation of alpha-promoter activity was assessed using both the chloramphenicol acetyl transferase (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 expression vector. The kinetics of stimulation of the alpha-promoter by PACAP-38 were similar to those seen with 8-Br-cAMP and vasoactive intestinal 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 transcription. We conclude that human placental choriocarcinoma cells possess functional receptors for PACAP-38, whose activation enhances cAMP formation, alpha-subunit gene transcription and interleukin-6 (IL-6) production.
Desai
B J
BJ
Department of Clinical Biochemistry, London Hospital Medical College, UK.
Burrin
J M
JM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002822:Choriocarcinoma / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000473:pathology
C495401:ADCYAP1 protein, human; D015292:Glycoprotein Hormones, alpha Subunit; D015850:Interleukin-6; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011993:Recombinant Fusion Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP