ABSTRACT
The aim of the present work was to study the effect of sex difference on the development of gastric ulcer induced by cold restraint stress [CRS] in albino rats. The study is a trial to evaluate the role of gonadal sex hormones in the pathophysiologic mechanism of CRS-induced gastric mucosal lesions through either exclusion by gonadectomy or resupplementation by exogenous administration of sex hormones [testosterone, T; estrogen, E and progesterone, P]. For this purpose, 112 adult albino rats [48 males and 64 non pregnant females] weighing between 200-250 grams were used in this study. Male rats were randomly classified into 6 equal groups: control [CM], orchidectomized [OM], orchidectomized with testosterone supplementation [OT], stressed [SM], orchidectomized stressed [OSM] and orchidectomized stressed with testosterone supplementation [OST]. Female rats were randomly classified into 8 equal groups: Control [CF], ovariectomized [OF], ovariectomized with estrogen supplementation [OE], ovariectomized with progesterone supplementation [OP], stressed [SF], ovariectomized stressed [OSF], ovariectomized stressed with estrogen supplementation [OSE] and ovariectomized stressed with progesterone supplementation [OSP]. Bilateral gonadectomy was done; in either sexes; 2 weeks before exposure to CRS. Hormonal supplementations were given for 7 days by subcutaneous injections starting 2 weeks after gonadectomy in respected groups. In male rats, orchidectomy significantly increased gastric juice [GJ] volume and pH and gastric mucosal [GM] nitrates; while it significantly decreased GJ acidity in OM group compared with CM group. No ulcerative lesions were observed in CM and OM groups. Injection of T significantly decreased GJ volume and pH and GM nitrates but significantly increased GJ acidity in OT group compared with CM and OM groups. T administration induced ulcerative lesions in OT group achieving an ulcer index [UI] of 11.33. CRS significantly reduced GJ volume, pH and mucin concentration [MC] and GM nitrates while it significantly increased GJ acidity and pepsin concentration [PC] and GM peroxides in SM group compared with CM group. CRS induced ulcerative lesion in all male rats achieving an UI of 21.25 in SM group. Orchidectomy before exposure to CRS significantly increased GJ volume and pH and GM nitrates and significantly decreased GJ acidity and GM peroxides in OSM group compared with SM group. Orchidectomy exhibited considerable protection against CRS ulcer development achieving U1 of 16.5 and protective index [PI] of 22.4 % in OSM group. Injection of T significantly reduced GJ volume and pH and GM nitrates and significantly increased GJ acidity and GM peroxides in OST group compared with OSM group and aggravated the ulcerative lesions achieving an UI of 22.6 and PI of 36.97% in OST group. In female rats, ovariectomy, significantly increased GJ acidity and MC; while it significantly decreased GJ pH and PC and GM nitrate in OF group compared with CF group. No ulcerative lesions were observed in CF and OF groups. Administration of E significantly decreased GJ volume, acidity and MC; while it significantly increased GJ pH and PC and GM nitrates in OE group compared with both CF and OF groups. E induced ulcerative lesions achieving an UI of 9.66 in OE group. Administration of P significantly increased GJ volume, pH and MC and significantly decreased GJ acidity, and PC and GM nitrates in OP group compared with both CF and OF groups. No ulcerative lesions were observed in OP group. CRS significantly increased GJ acidity and PC and GM peroxides; while it reduced significantly GJ volume, pH and MC and GM nitrates in SF group compared with CF group. CRS induced ulceration in all rats achieving an UI of 18.3 in SF group. Ovariectomy before exposure to CRS significantly decreased GJ pH and PC and GM nitrates; while it significantly increased GJ volume, acidity and MC and GM peroxides in OSF group compared with SF group. Although GM lesions were noted in OSF achieving an UI of 13.3, ovriectomy exhibited protection against CRS-induced GM ulceration and the PI was 27.34. Administration of E significantly decreased GI volume, acidity and MC and GM peroxides; while it significantly increased GJ pH and PC and GM nitrates in OSE group compared with OSF group. E aggravated GM lesions in OSE group achieving an UI of 20.9 and PI of - 56.9. On the other hand, giving P significantly decreased GJ acidity and PC and significantly increased GJ volume, pH and MC in OSP group compared with OSF group. P imparted a protective effect against CRS GM lesions achieving an UI of 9.5 and PI of 12.6 in OSP
In conclusion, a gender difference in CRS-induced GM ulcer development has been found in the present work, being more predominant in male than in female albino rats. The male sex hormone; T is absolutely ulcerogenic and orchidectomy offered protection. The female sex hormone; P was absolutely protective, while E potentiated some aggressive factors and enhanced other protective mechanisms with the net effect being ulcerogenic. Ovariectomy offered gastric protection against CRS-induced ulceration. It is therefore, probable that the protective effect of P can restraint the ulcerogenic effect of E to some extent and therefore lower the gastric UI in females than in males