Estrogen receptor α36 mediates a bone-sparing effect of 17β-estrodiol in postmenopausal women.
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.
Xie
Hui
H
Institute of Endocrinology and Metabolism, Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
Sun
Mei
M
Liao
Xiao-Bo
XB
Yuan
Ling-Qing
LQ
Sheng
Zhi-Feng
ZF
Meng
Ji-Cai
JC
Wang
Dan
D
Yu
Zhi-Yong
ZY
Zhang
Lei-Yi
LY
Zhou
Hou-De
HD
Luo
Xiang-Hang
XH
Li
Hui
H
Wu
Xian-Ping
XP
Wei
Qi-You
QY
Tang
Si-Yuan
SY
Wang
Zhao-Yi
ZY
Liao
Er-Yuan
EY
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
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