Cell proliferation and death in the gastric epithelium of developing rats after glucocorticoid treatments.
Glucocorticoids take part in the intense morphofunctional modifications that occur in the gastric mucosa during fetal and postnatal development. Two studies were designed to evaluate corticoids role in gastric cell proliferation and apoptosis in developing rats: in vivo, using suckling animals; in vitro, using gastric explants obtained from 20-day fetuses. These explants were cultured in DMEM/F12 medium treated or not with 50 ng/ml of corticosterone; after 22 hr, vincristine was added to the medium for 2 hr to block mitosis. The metaphasic index decreased significantly after the 24-hr treatment (controls: 1.52 +/- 0.53; treated: 0.40 +/- 0.21) and apoptotic cells were visualized under light and electron microscopy. Fifteen-day-old rats were treated with hydrocortisone (25 mg/Kg) for 3 days, and injected with BrDU (100 mg/Kg) 1 hr before sacrifice on the 18th day. BrDu-labeled and non-labeled cells were counted to determine the labeling index of epithelial cells. As apoptotic cells are rapidly eliminated, other animals were treated for only 2-3 hr. Sections were investigated for the presence of apoptotic cells, using morphological criteria and TUNEL labeling. Hydrocortisone significantly reduced the labeling index (controls: 15.6 +/- 1.6 vs. treated: 11.7 +/- 1.1), besides altering the body weight gain. Hydrocortisone treatment doubled the number of apoptotic cells after 2 hr, and quadruplicated it after 3 hr. The results demonstrated that glucocorticoids inhibit cell proliferation in the gastric epithelium of fetuses and suckling rats and increase apoptotic rates, suggesting the exit from cell cycle.
Gama
P
P
Departmento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil. patgama@usp.br
Goldfeder
E M
EM
de Moraes
J C
JC
Alvares
E P
EP
D000818:Animals; D000833:Animals, Suckling; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology*; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000196:embryology; D006854:Hydrocortisone / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008297:Male; D008940:Mitotic Index; D023421:Models, Animal; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D001973:Bromodeoxyuridine; D003345:Corticosterone; D006854:Hydrocortisone