TY - JOUR

T1 - Chronic systemic treatment with epidermal growth factor in pigs causes pronounced urothelial growth with accumulation of glycoconjugates

AU - Vinter-Jensen, Lars

AU - Juhl, C O

AU - Djurhuus, Jens Christian

AU - Poulsen, Steen Seier

AU - Dajani, E Z

AU - Brown, K D

AU - Orntoft, T F

AU - Teglbjaerg, P S

AU - Nexø, Ebba

PY - 1995/11

Y1 - 1995/11

N2 - Epidermal growth factor (EGF) is present in large amounts in the urine, but the effects of systemically administered EGF on the urinary tract have not been described previously. In the present paper, we describe a potent growth induction of EGF on the urinary tract. Goettingen minipigs were treated with solvent (n = 5), EGF 30 micrograms/kg/day (n = 6) for 4 weeks, or EGF 30 micrograms/kg/day for 5 weeks followed by 3 weeks of recovery (n = 5). The ureters and bladders were examined by routine histology and electron microscopy and were immunostained for proliferating cell nuclear antigen. Four weeks of EGF treatment increased the median cross sectional area of the ureter fourfold with growth of all wall layers. The urothelium was widened from 5 cell layers in the controls to 10 in the EGF-treated animals. Proliferating cell nuclear antigen immunostaining revealed an increased mitotic activity in the basal zone of the urothelium. In the luminal zone, glycoconjugates accumulated in goblet cells, in cells with intracytoplasmic lumina, and beneath the luminal cell membrane in the umbrella cells. Our studies present a new experimental approach to growth induction of the urinary tract. The findings implicate the EGF system in regulating urothelial growth and glycoconjugate biosynthesis.

AB - Epidermal growth factor (EGF) is present in large amounts in the urine, but the effects of systemically administered EGF on the urinary tract have not been described previously. In the present paper, we describe a potent growth induction of EGF on the urinary tract. Goettingen minipigs were treated with solvent (n = 5), EGF 30 micrograms/kg/day (n = 6) for 4 weeks, or EGF 30 micrograms/kg/day for 5 weeks followed by 3 weeks of recovery (n = 5). The ureters and bladders were examined by routine histology and electron microscopy and were immunostained for proliferating cell nuclear antigen. Four weeks of EGF treatment increased the median cross sectional area of the ureter fourfold with growth of all wall layers. The urothelium was widened from 5 cell layers in the controls to 10 in the EGF-treated animals. Proliferating cell nuclear antigen immunostaining revealed an increased mitotic activity in the basal zone of the urothelium. In the luminal zone, glycoconjugates accumulated in goblet cells, in cells with intracytoplasmic lumina, and beneath the luminal cell membrane in the umbrella cells. Our studies present a new experimental approach to growth induction of the urinary tract. The findings implicate the EGF system in regulating urothelial growth and glycoconjugate biosynthesis.

KW - Animals

KW - Epidermal Growth Factor

KW - Epithelium

KW - Female

KW - Glycoconjugates

KW - Humans

KW - Hyperplasia

KW - Injections, Subcutaneous

KW - Male

KW - Proliferating Cell Nuclear Antigen

KW - Swine

KW - Swine, Miniature

KW - Ureter

M3 - Journal article

C2 - 7485396

VL - 147

SP - 1330

EP - 1338

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 5

ER -