Phytoestrogens regulate vitamin D metabolism in the mouse colon: relevance for colon tumor prevention and therapy.
Soybean products are highly represented in the traditional Asian diet. Major components of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of prostate and mammary tumors and possibly also of colon cancer in countries such as China and Japan. Serum 1,25-dihydroxyvitamin D3 level is inversely related to incidence of some cancers. Levels are determined by skin exposure to ultraviolet light or, to a minor extent, nutritional uptake and by subsequent conversion of the precursor vitamin D to the active hormone by the cytochrome P450 hydroxylases CYP27A1, CYP27B1 (responsible for synthesis) and CYP24 (responsible for catabolism) in liver and kidney. However, vitamin D synthesis is also found in colonocytes and is enhanced during incipient malignancy. This may indicate an autocrine/paracrine role for this differentiation-inducing hormone in defense against progression. We were able to demonstrate that either a single large oral dose of genistein or feeding soy protein for 4 mo elevated CYP27B1 and decreased CYP24 expression in the mouse colon. Our data therefore suggest that an inverse correlation of soy product consumption with colon tumor incidence may be consequent to enhanced colonic synthesis of the antimitotic hormone 1,25-dihydroxyvitamin D3.
Kállay
Enikö
E
Department of Pathophysiology, University of Vienna Medical School, Vienna, Austria.
Adlercreutz
Herman
H
Farhan
Hesso
H
Lechner
Daniel
D
Bajna
Erika
E
Gerdenitsch
Waltraud
W
Campbell
Moray
M
Cross
Heide S
HS
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004044:Dietary Proteins / Q000008:administration & dosage; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D007529:Isoflavones; D051379:Mice; D008810:Mice, Inbred C57BL; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D030262:Soybean Proteins / Q000008:administration & dosage / Q000737:chemistry; D013250:Steroid Hydroxylases / Q000235:genetics; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D004044:Dietary Proteins; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger; D030262:Soybean Proteins; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D019833:Genistein; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase