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-1 beta and
TNF-alpha.
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-1 beta and
TNF-alpha 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-1 beta and
TNF-alpha 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.