title: Estrogen receptor α36 mediates a bone-sparing effect of 17β-estrodiol in postmenopausal women.
abstract: Recently, a membrane-based estrogen receptor (ER), ER-α36, was identified and cloned that transduces membrane-initiated estrogen signaling such as activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Here we show that the postmenopausal level of estradiol (E2) induces mitogenic, antiapoptotic, and antiosteogenic effects and proapoptotic effects in postmenopausal osteoblasts and osteoclasts with high levels of ER-α36 expression, respectively. We also found that ER-α36 mediated the effects of postmenopausal-level E(2) on proliferation, apoptosis, and differentiation of osteoblasts through transient activation of the MAPK/ERK pathway, whereas ER-α36-mediated postmenopausal-level E(2) induces apoptosis of osteoclasts through prolonged activation of the MAPK/ERK pathway with the involvement of reactive oxygen species. We also show that the levels of ER-α36 expression in bone are positively associated with bone mineral density but negatively associated with bone biochemical markers in postmenopausal women. Thus the higher levels of ER-α36 expression are required for preserving bone mass in postmenopausal and menopausal women who become osteoporotic if ER-α36-mediated activities are dysregulated.
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Liao
authors.forename: Ling-Qing
authors.initials: LQ
authors.lastname: Yuan
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Sheng
authors.forename: Ji-Cai
authors.initials: JC
authors.lastname: Meng
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yu
authors.forename: Lei-Yi
authors.initials: LY
authors.lastname: Zhang
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
authors.forename: Xiang-Hang
authors.initials: XH
authors.lastname: Luo
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Wu
authors.forename: Qi-You
authors.initials: QY
authors.lastname: Wei
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Tang
authors.forename: Zhao-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D015415:Biomarkers; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D005419:Flavonoids; D008934:Mitogens; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one