Stimulation of DNA synthesis in pancreatic duct cells by gastrointestinal hormones: interaction with other growth factors.
Pancreatic duct cells of the Syrian hamster were grown as monolayers on thin layers of type I collagen coated onto microporous membranes. The effects of a number of potential trophic factors were tested by their ability to increase [3H]thymidine incorporation into cellular DNA. To measure the effect of growth factors, cells were subjected to a period of growth factor depletion to induce a state of partial quiescence in DNA synthesis. Cells responded with a significant increase in thymidine incorporation after the addition of epidermal growth factor (EGF) alone or a growth factor mixture containing EGF plus insulin, transferrin, selenium, linoleic acid, bovine pituitary extract, triiodothyronine, and dexamethasone. When the serum substitute, Nu Serum IV (5%, vol/vol), was added to this mixture, addition of several gastrointestinal (GI) hormones including secretin, vasoactive intestinal polypeptide (VIP), bombesin, and gastrin caused significant increases in thymidine incorporation at concentrations of 0.01-1 microM. At 1 microM, these hormones stimulated DNA synthesis relative to their respective control in the order secretin (178%) greater than bombesin (153%) greater than VIP (138%) greater than gastrin (126%). Cholecystokinin octapeptide, a known trophic factor for pancreatic acinar cells, did not cause significant increases in thymidine incorporation in cultured duct cells. These results suggest that pancreatic duct cells possess receptors for a number of GI hormones and respond to the trophic effects of hormones known to stimulate pancreatic growth in vivo.
Mangino
M M
MM
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611.
Hubchak
S
S
Scarpelli
D G
DG
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis*; D004347:Drug Interactions; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005782:Gels; D006133:Growth Substances / Q000494:pharmacology*; D008567:Membranes, Artificial; D008647:Mesocricetus; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D005768:Gastrointestinal Hormones; D005782:Gels; D006133:Growth Substances; D008567:Membranes, Artificial; D003094:Collagen; D004247:DNA; D013936:Thymidine