Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas.
OBJECTIVE
Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and the EGF receptor are often overexpressed in chronic pancreatitis and in malignant pancreatic growth. Transgenic mice overexpressing TGF-alpha develop tissue changes in the pancrease resembling changes found in chronic pancreatitis. The effects of systemic treatment with EGF on the porcine pancrease were investigated in this study.


METHODS
Mature Goettingen minipigs were treated with solvent (n = 5), EGF (30 micrograms.kg-1.day-1; n = 6) for 4 weeks, or EGF (30 micrograms.kg-1.day-1; n = 5) for 5 weeks followed by 3 weeks of recovery. Pancreata were studied by routine histological examination and electron microscopy and were immunostained for proliferating cell nuclear antigen (PCNA).


RESULTS
In the EGF-treated animals, mainly larger interlobular ducts of the pancreas appeared to be considerably hyperplastic, with an increased number of nuclei that stained for PCNA. The epithelia of these ducts were increased in height, with accumulations of glycoconjugates in the columnar cells and in an increased number of goblet cells.


CONCLUSIONS
A new approach to experimentally induced hyperplastic changes of the excretory ducts of the pancreas is presented. Because ductal changes with glycoconjugate accumulations are common features of chronic pancreatitis and pancreatic cancer, the findings may be relevant to the pathogeneses of these conditions.
Vinter-Jensen
L
L
Department of Clinical Biochemistry, KH, Aarhus University Hospital, Denmark.
Juhl
C O
CO
Teglbjaerg
P S
PS
Poulsen
S S
SS
Dajani
E Z
EZ
Nexø
E
E
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006001:Glycoconjugates / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009077:Mucins / Q000032:analysis; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D010191:Pancreatic Polypeptide / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D013004:Somatostatin / Q000032:analysis; D013552:Swine; D013556:Swine, Miniature
D006001:Glycoconjugates; D009077:Mucins; D018809:Proliferating Cell Nuclear Antigen; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D004815:Epidermal Growth Factor