title: Mutual antagonism of estrogen receptors alpha and beta and their preferred interactions with steroid receptor coactivators in human osteoblastic cell lines.
abstract: Estrogen is a major sex steroid that affects the growth, maintenance, and homeostasis of the skeleton. Two isoforms of the estrogen receptor (ERalpha and ERbeta) mediate the transcriptional effects of estrogen. Although both isoforms of ER are present and functional in some human osteoblast (OB) cell lines, there is minimal information on the differential regulation of transcription by ERalpha and ERbeta homo- or heterodimers. This report demonstrates that ERalpha and ERbeta coexpression decreases the transcriptional capacity (relative to each ER isoform alone) on an estrogen response element-dependent reporter gene in OBs but not in other non-osteoblastic cell lines. These data suggest that ERalpha and ERbeta coexpression can differentially influence the degree of transcriptional activation in certain cell types. Interestingly, the overexpression of the steroid hormone receptor coactivator-1 (SRC1) resulted in preferential transcriptional enhancement by ERbeta as well as coexpressed ERalpha and ERbeta, whereas SRC2 overexpression appeared to preferentially enhance ERalpha transactivation. SRC3 overexpression failed to enhance estrogen-dependent transcription of any ER combination in OBs. Similar overexpression experiments in COS7 cells exhibited preferential enhancement of ERalpha function with all SRCs, including SRC3. Our data also demonstrated that SRC3 mRNA is reduced in osteoblastic cells, suggesting that SRC3 may have only a minor role in these cells. These data suggest that the transactivation capacity of various ER isoforms is both SRC species and cell type dependent.
authors.affiliation: Department of Molecular Biology and Biochemistry, Mayo Clinic and Mayo Foundation, 200 1st Avenue SW, Rochester, Minnesota 55905, USA. Monroe.David@mayo.edu
authors.forename: D G
authors.initials: DG
authors.lastname: Monroe
authors.forename: S A
authors.initials: SA
authors.lastname: Johnsen
authors.forename: M
authors.initials: M
authors.lastname: Subramaniam
authors.forename: B J
authors.initials: BJ
authors.lastname: Getz
authors.forename: S
authors.initials: S
authors.lastname: Khosla
authors.forename: B L
authors.initials: BL
authors.lastname: Riggs
authors.forename: T C
authors.initials: TC
authors.lastname: Spelsberg
mesh_terms: D000123:Acetyltransferases; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019556:COS Cells; D002460:Cell Line; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D051548:Histone Acetyltransferases; D006801:Humans; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D010006:Osteoblasts / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D051958:Nuclear Receptor Coactivator 2; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538866:NCOA3 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3