17β-Estradiol suppresses Helicobacter pylori-induced gastric pathology in male hypergastrinemic INS-GAS mice

• Published in: Carcinogenesis (New York) Vol. 32; no. 8; pp. 1244 - 1250
• Main Authors: Ohtani, Masahiro, Ge, Zhongming, García, Alexis, Rogers, Arlin B., Muthupalani, Sureshkumar, Taylor, Nancy S., Xu, Shilu, Watanabe, Koichiro, Feng, Yan, Marini, Robert P., Whary, Mark T., Wang, Timothy C., Fox, James G.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-08-2011
• Subjects: Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Biological and medical sciences; Cancer Prevention; Carcinogenesis, carcinogens and anticarcinogens; Human bacterial diseases; Infectious diseases; Medical sciences; Tumors; Stomach; Spirillales; Digestive system; Estrogen; Rodentia; Spirillaceae; 17β-Estradiol; Male; Ovarian hormone; Infection; Vertebrata; Anatomic pathology; Mammalia; Helicobacter pylori; Mouse; Animal; Bacteriosis; Bacteria; Sex steroid hormone
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgr072

Helicobacter pylori-associated gastric cancer is male predominant and animal studies suggest that sex hormones influence gastric carcinogenesis. We investigated the effects of 17β-estradiol (E2) or castration on H.
pylori-induced gastritis in male INS-GAS/FVB/N (Tg(Ins1-GAS)1Sbr) mice. Comparisons were made to previously evaluated sham (n = 8) and H.
pylori-infected (n = 8), intact male INS-GAS mice which had developed severe corpus gastritis accompanied by atrophy, hyperplasia, intestinal metaplasia and dysplasia of the epithelium within 16 weeks postinfection (all P < 0.01). Castration at 8 weeks of age had no sparing effect on lesions in uninfected (n = 5) or H.
pylori-infected mice (n = 7) but all lesion subfeatures were attenuated by E2 in H.
pylori-infected mice (n = 7) (P < 0.001). Notably, inflammation was not reduced but glandular atrophy, hyperplasia, intestinal metaplasia and dysplasia were also less severe in uninfected, E2-treated mice (n = 7) (P < 0.01). Attenuation of gastric lesions by E2 was associated with lower messenger RNA (mRNA) expression of interferon (IFN)-γ (P < 0.05) and interleukin (IL)-1β (P < 0.004), and higher IL-10 (P < 0.02) as well as decreased numbers of Foxp3+ regulatory T cells when compared with infected intact males. Infected E2-treated mice also developed higher Th2-associated anti-H.
pylori IgG1 responses (P < 0.05) and significantly lower Ki-67 indices of epithelial proliferation (P < 0.05). E2 elevated expression of mRNA for Foxp3 (P < 0.0001) and IL-10 (P < 0.01), and decreased IL-1β (P < 0.01) in uninfected, intact male mice compared with controls. Therefore, estrogen supplementation, but not castration, attenuated gastric lesions in H.
pylori-infected male INS-GAS mice and to a lesser extent in uninfected mice, potentially by enhancing IL-10 function, which in turn decreased IFN-γ and IL-1β responses induced by H.
pylori.