Abstract
Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO) to the ApcMin/+ mouse, a model for spontaneous intestinal polyposis. PRKO-ApcMin/+mice exhibited no change in polyp number, size or localization compared to ApcMin/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.
Highlights
The Women’s Health Initiative (WHI) was launched in 1991 to conduct medical research into some of the major health problems of older women
Hypothesizing that the progesterone receptor is the main mediator of the effect of progestins, we set out to examine the expression of the progesterone receptor in the epithelium of the small and large intestine (Fig. 1)
All antibodies reacted with progesterone receptor (PR) in the mouse uterus, which was used as a positive control (Fig. 1E) but not with the uterus of mice that lack the PR (PRKO mice, data not shown)
Summary
The Women’s Health Initiative (WHI) was launched in 1991 to conduct medical research into some of the major health problems of older women. A substantial 40% risk reduction (P = 0.003) for colon cancer development was observed in women that received the combination therapy [4], whereas the risk of colorectal cancer was slightly but not significantly increased by treatment with estrogens alone. Based on these results, progestins have been suggested as putative chemopreventive agents for colon cancer [5,6], the mechanism of action by which they work in the intestine remains obscure
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
