Reciprocal expression of ER alpha and ER beta is associated with estrogen-mediated modulation of intestinal tumorigenesis

Menopausal hormone replacement therapy has been widely used to alleviate th e symptoms of menopause and to decrease the detrimental effects of ovarian hormone loss on bone density and cardiovascular health, Multiple studies of colorectal cancer epidemiology also support a role for hormone replacement therapy in prevention of colorectal cancer, We studied the effect of ovari ectomy and estrogen replacement on tumor formation in C57BL/6J-Min/+ (Min/) mice, animals that bear a germline mutation in murine Ape. These mice dev elop multiple intestinal tumors that show loss of wild-type Ape protein, Af ter ovariectomy, intestinal adenomas in Min/+ mice increased by 77% (P = 0. 0004), Ovariectomized Min/+ mice that were treated with a replacement dose of 17 beta -estradiol had the same number of tumors as Min/+ mice that were neither castrated nor treated with estrogen replacement (P = 0.85), Examin ation of estrogen receptor (ER) levels in intestinal tissue by immunoblot s howed changes in relative expression levels of ER alpha and ER beta with hi ghest ER alpha and lowest ER beta expression in the normal-appearing intest ine of Min/+ mice, and lowest ER alpha and highest ER beta expression in th e enterocytes of animals that received 17 beta -estradiol. These results su ggest that endogenous estrogens protect against Ape-associated tumor format ion and that tumor prevention by 17 beta -estradiol is associated with an i ncrease in ER beta and a decrease in ER alpha expression in the target tiss ue.