Dual effect of female sex steroids on drug-induced gastroduodenal ulcers in the rat.
Since the sexual dimorphism of gastroduodenal ulcers is well known and might possibly relate to the actions of sex hormones, we studied the role of the female sex steroids, progesterone and 17beta-estradiol in cysteamine-induced mucosal ulcers in female Wistar rats (200-220 g). Administration of cysteamine (400 mg/kg, s.c.) provoked macroscopic gastroduodenal mucosa injury as assessed planimetrically, an increase in microvascular permeability in the stomach and the duodenum as assessed by extravasation of radiolabelled albumin, and decreased gastroduodenal mucus levels as assessed by the Alcian blue technique. Ovariectomy (2 weeks before cysteamine) decreased plasma 17beta-estradiol level as assessed by radioimmunoassay, gastroduodenal macroscopic injury and albumin extravasation, and increased mucus levels following cysteamine challenge. Administration of progesterone (10-50 mg/kg/week, s.c.) attenuated in a dose-dependent manner cysteamine-induced gastroduodenal mucosa injury and microvascular leakage, while it increased mucus levels in the stomach and the duodenum. In contrast, administration of 17beta-estradiol (1-5 mg/kg/week, s.c.) dose-dependently augmented gastric and duodenal macroscopic mucosa lesions and microvascular injury provoked by cysteamine, and caused a further reduction in gastroduodenal mucus levels observed after cysteamine administration. In different experiments, ovariectomy decreased indomethacin-induced gastroduodenal injury. The injection of 17beta-estradiol (1-5 mg/kg/week) did not affect gastroduodenal damage, while treatment with progesterone (10-50 mg/kg/week) protected against indomethacin-provoked mucosa ulcers. It is concluded that female sex steroids play a role in drug-induced gastroduodenal ulcers by modulating microvascular permeability and mucus secretion.
Drago
F
F
Institute of Pharmacology, University of Catania Medical School, Italy. fdrago@tin.it
Montoneri
C
C
Varga
C
C
Làszlò
F
F
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003543:Cysteamine / Q000633:toxicity; D004381:Duodenal Ulcer / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000503:physiopathology; D007213:Indomethacin / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control
D011374:Progesterone; D004958:Estradiol; D003543:Cysteamine; D007213:Indomethacin