title: DHEA suppresses longitudinal bone growth by acting directly at growth plate through estrogen receptors.
abstract: Dehydroepiandrosterone (DHEA) is produced by the adrenal cortex and is the most abundant steroid in humans. Although in some physiological and pathological conditions the increased secretion of DHEA and its sulfated form is associated with accelerated growth rate and skeletal maturation, it is unclear whether DHEA can affect longitudinal bone growth and skeletal maturation by acting directly at the growth plate. In our study, DHEA suppressed metatarsal growth, growth plate chondrocyte proliferation, and hypertrophy/differentiation. In addition, DHEA increased the number of apoptotic chondrocytes in the growth plate. In cultured chondrocytes, DHEA reduced chondrocyte proliferation and induced apoptosis. The DHEA-induced inhibition of metatarsal growth and growth plate chondrocyte proliferation and hypertrophy/differentiation was nullified by culturing metatarsals with DHEA in the presence of ICI 182,780, an inhibitor of estrogen receptor, but not in the presence of Casodex, an inhibitor of androgen receptor. Lastly, nuclear factor-κB DNA binding activity was inhibited by the addition of DHEA in the medium of cultured chondrocyte. Our findings indicate that DHEA suppressed bone growth by acting directly at growth plate through estrogen receptor. Such growth inhibition is mediated by decreased chondrocyte proliferation and hypertrophy/differentiation and by increased chondrocyte apoptosis.
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Medical College of Xi'an Jiaotong University, 76 Yanta West Road, Xi'an 710061, People's Republic of China. sunhongzhi@mail.xjtu.edu.cn
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Sun
authors.forename: Weijin
authors.initials: W
authors.lastname: Zang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Shufang
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001846:Bone Development / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006132:Growth Plate / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D009924:Organ Culture Techniques; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D051996:Transcription Factor RelA; D003687:Dehydroepiandrosterone