Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in the delayed healing of lingual and gastric ulcerations by testosterone |
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Authors: | A Machowska T Brzozowski Z Sliwowski M Pawlik P C Konturek R Pajdo A Szlachcic D Drozdowicz M Schwarz J Stachura S J Konturek W W Pawlik |
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Institution: | (1) Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland;(2) Department of Pathomorphology, Jagiellonian University Medical College, Cracow, Poland;(3) Department of Medicine I, University of Erlangen, Nuremberg, Germany |
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Abstract: | Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study
of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects
of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral
orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins,
as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1β and TNF-α. Testosterone (0.01–10
mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day,
this hormone significantly raised gastric acid secretion and plasma IL-1β and TNF-α levels. Attenuation of plasma testosterone
levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing
plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and
delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing,
and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1β and TNF-α and, in the case of gastric ulcers,
an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the
deleterious effects of testosterone on ulcer healing.
Received 17 October 2006; revised 2 July 2007; accepted 5 July 2007 |
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Keywords: | Testosterone epidermal growth factor lingual ulcer gastric ulcer orchidectomy salivectomy gastric secretion gastric blood flow interleukin-1beta tumor necrosis factor-alpha |
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