Estrogen administration may lower colon cancer risk by up-regulating 1,25-dihydroxyvitamin D3 in colorectal epithelium Heide Cross, Enikoe Kallay, Petr Protiva, Martin Lipkin, Eleanor Dreyhaupt, Peter Holt. Medical University of Vienna, Vienna, Austria and Strang Cancer Research Laboratory, New York, NY. Extrarenal production of 1,25-dihydroxyvitamin D3 in human colonic epithelium has recently been suggested as a physiological defense mechanism against colorectal cancer. Since both vitamin D receptor as well as 1,25-dihydroxyvitamin D3 (CYP27 B1) protein demonstrate increased expression in early colorectal tumors compared to adjacent normal epithelium, an autocrine mode of growth control by elevated mucosal 1,25-dihydroxyvitamin D3 levels has been postulated. Estrogen administration also appears to reduce colorectal cancer risk although mechanisms of action have not been clarified. Estrogen increases the intestinal absorption of calcium, and our recent findings suggest it may enhance the activity of vitamin D3 in colorectal epithelium. In this study we evaluated the effects of estradiol administered to 10 post-menopausal women who were maintained on controlled nutritional intakes, with estradiol given in amounts sufficient to raise serum values to premenopausal levels for 4 weeks. Rectal biopsies were taken before and after administration of estradiol. Following estradiol administration, 1á-hydroxylase mRNA, determined by real-time-PCR increased significantly (p<0.01), without changes occurring in CYP24 or caspase 3 mRNA. Immunohistochemical measurements confirmed that CYP27 B1 was present in rectal epithelial cells. Trends toward correlations between CYP27 B1 and CYP24, as well as between CYP27 B1 and caspase 3 mRNA were seen. No significant changes were observed in ERá, ERâ and vitamin D receptor mRNA, nor in circulating 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3. We conclude that estrogen administration in protecting against colorectal neoplasia modifies the metabolism of vitamin D3 in colorectal epithelium, resulting in increased levels of 1,25-dihydroxyvitamin D3 the active intracellular form of vitamin D. Since vitamin D has been shown to decrease colorectal cancer risk estrogen may function at least in part by its ability to increase the activity of vitamin D and its protective effect against colon cancer. Abstract 1601, AACR 2005 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.