Sex disparity in colonic adenomagenesis involves promotion by male hormones, not protection by female hormones
James M. Amos-Landgraf,Jarom Heijmans,Mattheus C. B. Wielenga,Elisa Dunkin,Kathy J. Krentz,Linda Clipson,Antwan G. Ederveen,Patrick G. Groothuis,Sietse Mosselman,Vanesa Muncan,Daniel W. Hommes,Alexandra Shedlovsky,William F. Dove,Gijs R. van den Brink +13 more
TLDR
It is found that castration reduced, and testosterone supplementation restored, the number of adenomas in the male rat and mouse colon, whereas ovariectomy and replacement of female hormones had no measureable effect on colonic adenomagenesis.Abstract:
It recently has been recognized that men develop colonic adenomas and carcinomas at an earlier age and at a higher rate than women. In the ApcPirc/+ (Pirc) rat model of early colonic cancer, this sex susceptibility was recapitulated, with male Pirc rats developing twice as many adenomas as females. Analysis of large datasets revealed that the ApcMin/+ mouse also shows enhanced male susceptibility to adenomagenesis, but only in the colon. In addition, WT mice treated with injections of the carcinogen azoxymethane (AOM) showed increased numbers of colonic adenomas in males. The mechanism underlying these observations was investigated by manipulation of hormonal status. The preponderance of colonic adenomas in the Pirc rat model allowed a statistically significant investigation in vivo of the mechanism of sex hormone action on the development of colonic adenomas. Females depleted of endogenous hormones by ovariectomy did not exhibit a change in prevalence of adenomas, nor was any effect observed with replacement of one or a combination of female hormones. In contrast, depletion of male hormones by orchidectomy (castration) markedly protected the Pirc rat from adenoma development, whereas supplementation with testosterone reversed that effect. These observations were recapitulated in the AOM mouse model. Androgen receptor was undetectable in the colon or adenomas, making it likely that testosterone acts indirectly on the tumor lineage. Our findings suggest that indirect tumor-promoting effects of testosterone likely explain the disparity between the sexes in the development of colonic adenomas.read more
Citations
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Suppressive effects of androgens on the immune system.
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The Regulation of Steroid Action by Sulfation and Desulfation
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Aberrant crypt foci of the colon as precursors of adenoma and cancer
Tetsuji Takayama,Shinichi Katsuki,Yasuo Takahashi,Moton Ohi,Shuichi Nojiri,Sumio Sakamaki,Junji Kato,Katsuhisa Kogawa,Hirotsugu Miyake,Yoshiro Nihsu +9 more
TL;DR: Aberrant crypt foci, particularly those that are large and have dysplastic features, may be precursors of adenoma and cancer.
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The mini-driver model of polygenic cancer evolution.
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Incidence and mortality of colorectal cancer in China, 2011.
TL;DR: The rate of colorectal cancer increased greatly with age, especially after 40 or 45 years old, especially for males in urban areas and in rural areas, which means targeted prevention and early detection programs should be carried out.
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