[Molecular mechanism of tissue-specific actions of sex steroid hormones and SERM for bone remodeling].

Female sex steroid hormone, estrogen, exerts a wide variety of biological actions including lipid metabolism and bone remodeling. Moreover, estrogen is known to be involved in many pathological states like osteoporosis, tumor incidence and tumor development of female reproductive organs. Most of such estrogen actions are believed to mediate transcriptional controls of a particular set of target genes by its nuclear receptor, estrogen receptor (ER). The products of the genes regulated by ER are responsible for the overt estrogen actions in the many estrogen target tissues. Reflecting the estrogen actions, two ER subtypes (alpha, beta) express in the bone and the other target tissues. ER is a hormone-dependent transcriptional factor and hormone binding is known to alter the structure of ER protein, following dissociation/recruitment of multiple co-regulator complexes. Synthetic ER ligands, SERM, are believed to cause the ligand type-specific alteration in ER structure. This SERM-induced structural alteration acquires the tissue-specific function of liganded ER, as SERM acts as an agonist for bone remodeling.