The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations.

Studies in different animal species and in humans have suggested that sex hormones influence gastric acid secretion and contribute to the integrity of the oral and gastroduodenal mucosa but the effect of male and female sex hormones on the healing of the preexisting ulcers in the oral cavity and stomach have not been studied. We compared the effects of major male hormone, testosterone, and female hormone, progesterone, on the healing of lingual and gastric ulcers induced by acetic acid technique in male rats with intact or removed testicles (testectomy) and female rats with intact or removed ovaries (ovariectomy). The gastric acid secretion was determined in rats with gastric ulcers equipped with chronic gastric fistula (GF). Rats were sacrificed at day 7 upon ulcer induction; the ulcer area was measured by planimetry and the lingual and gastric blood flow (GBF) was determined by H(2)-gas clearance method and venous blood was collected for determination of plasma gastrin and plasma proinflammatory cytokine interleukin (IL)-1 beta levels. Gastric acid output from GF rats was significantly reduced while plasma gastrin was significantly enhanced in testectomized animals as compared to those in intact control rats and these effects were reversed by supplementation of testectomized animals with testosterone. The area of lingual and gastric ulcers in placebo-control rats decreased significantly at day 7 and this effect was significantly accelerated by testectomy or ovariectomy. In contrast, testosterone significantly delayed ulcer healing while producing a significant fall in the gastric blood flow and lingual blood flow determined at the margin of these ulcers. Treatment with progesterone significantly accelerated ulcer healing and increased the gastric and lingual blood flow at margin of these ulcers. Testosterone applied alone or supplemented in testectomized animals produced the significant increment in plasma IL-1 beta levels as compared to the respective levels of this cytokine in placebo-control animals. We conclude that: 1) major male (testosterone) and female (progesterone) sex hormones exhibit opposite effect on healing of preexisting ulcers in the oral cavity and stomach because testosterone markedly delayed while progesterone significantly accelerated this healing; 2) testosterone-induced delay in ulcer healing involves the fall in the gastric microcirculation at the margin of lingual and gastric ulcers and the excessive production and release of proinflammatory cytokine IL-1 beta; and 3) testectomy improves the gastric ulcer healing due to inhibition of gastric acid secretion and the rise in plasma gastrin, which exerts gastroprotective, trophic and ulcer healing action on the gastric mucosa.