Abstract:
:The effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of the phytoestrogens daidzein, genistein, and coumestrol was investigated using Bcrp(-/-) mice. Expression of the genes for either mouse Bcrp or human BCRP in MDCK II cells induced apically directed transport of the three phytoestrogens, whereas their transcellular transport was identical in mock and LLC-PK1 cells expressing mouse Mdr1a. After oral administration, the plasma levels of daidzein and genistein were increased in Bcrp(-/-) mice, but only a minimal change was observed for coumestrol. At steady state, tissue-to-plasma concentration ratios of the three phytoestrogens in the brain and testis of wild-type mice were very small and similar to those of [(14)C]inulin, whereas those were significantly increased in the brain and testis of Bcrp(-/-) mice. The largest increases were observed with genistein (9.2- and 5.8-fold in the brain and testis, respectively). The distributions of genistein in the epididymis and fetus, but not the ovary, were also increased in Bcrp(-/-) mice. The Bcrp protein was localized in the luminal membrane of the endothelial cells in the testis and the body of the epididymis and in both the luminal and abluminal side of ducts in the head of the epididymis. These results suggest that Bcrp limits the oral availability and distribution into the brain and testis, epididymis, and fetus of phytoestrogens.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Enokizono J,Kusuhara H,Sugiyama Ydoi
10.1124/mol.107.034751subject
Has Abstractpub_date
2007-10-01 00:00:00pages
967-75issue
4eissn
0026-895Xissn
1521-0111pii
mol.107.034751journal_volume
72pub_type
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