[Molecular mechanism of tissue-specific actions of SERM].
SERM like tamoxifene and raloxifene is a synthetic ligand for estrogen receptor (ER), and exert tissue-specific actions in many target tissues as an agonist/antagonist thorough modifying the ER function. ER is a member of the nuclear steroid/thyroid hormone, fat-soluble vitamin receptor gene superfamily and acts as a ligand-inducible factor. The ligand-dependent transactivation of ER requires direct interactions of co-regulators through its C-terminal helix-12. Ligand binding to ER causes structural alteration with the helix 12 shifting, but such structural alterations appear distinct among the ligand types. Tissue-specific actions of SERM are speculated to exert through ligand-type-specific alterations in structure with consequent recruitments of regulators.
Kato
Shigeaki
S
The Institute of Molecular and Cellular Biosciences,The University of Tokyo.