Prostaglandin E2-induced hyperplasia of the rat antral epithelium is followed by a secondary inhibition of the mitotic activity.
The aim of the study was to examine the mitotic activity in the antral and duodenal epithelium of Sprague-Dawley rats given trophic doses of E2 prostaglandins during a prolonged period of time. Natural prostaglandin E2 (dose range: 0.2-5.0 mg.k-1) and 15 (R) 15 methyl prostaglandin E2 (dose range: 0.03-2.0 mg.kg-1) were administered for 11 days, and mitoses were arrested with vincristine for 4 h before estimation of the cumulative mitotic index. A dose-related hyperplasia of the antral glands was observed after treatment with prostaglandin E2 and the synthetic analogue (p less than 0.05). The proliferative zone was enlarged in rats treated with high doses of the analogue but natural prostaglandin E2 did not affect the limits of the proliferative zone. A dose-related reduction of the mitotic index was observed in animals treated with prostaglandin E2 despite the presence of hyperplastic changes. All doses of the analogue induced antral hyperplasia without affecting the mitotic index except in rats given the highest dose who had a significantly lower mitotic index than controls (p less than 0.05). Hyperplasia of both crypts and villi was observed in the duodenum of rats given high doses of E2 prostaglandins (p less than 0.05) whereas the mitotic index and the growth fraction were not affected by treatments. It is concluded that hyperplasia by prostaglandins is developed in absence of changes of the mitotic activity. The observed reduction of the mitotic index is interpreted as a secondary phenomenon, possibly mediated by a regulatory mechanism of cell proliferation which is triggered to reduce further epithelial growth. It is suggested that prostaglandin E2 might influence such regulatory mechanisms.
Uribe
A
A
Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
Garberg
L
L
D000284:Administration, Oral; D000818:Animals; D001101:Arbaprostil / Q000633:toxicity*; D002452:Cell Count / Q000187:drug effects; D015232:Dinoprostone / Q000633:toxicity*; D004386:Duodenum / Q000187:drug effects / Q000473:pathology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D006965:Hyperplasia / Q000139:chemically induced; D008938:Mitosis / Q000187:drug effects*; D011459:Prostaglandins E, Synthetic / Q000633:toxicity*; D011706:Pyloric Antrum / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011459:Prostaglandins E, Synthetic; D015232:Dinoprostone; D001101:Arbaprostil