title: Estradiol determines the effects of PTH on ERα-dependent transcription in MC3T3-E1 cells.
abstract: Bone remodeling is a continuous process regulated by several hormones such as estrogens and parathyroid hormone (PTH). Here we investigated the influence of PTH on estrogen receptor alpha (ERα)-dependent transcriptional activity in MC3T3-E1 osteoblasts. Cells that were transfected with an ER-responsive reporter plasmid and treated with PTH showed increased luciferase activity. However, in the presence of 17β-estradiol, we observed that PTH inhibited ERα-mediated transcription. cAMP mimicked the effects by PTH, and the findings were confirmed in COS-1 cells transfected with expression vector encoding the catalytic subunit of cAMP-dependent protein kinase (PKA). Furthermore, PTH exhibited specific effects on the mRNA expression of the decoy receptor osteoprotegerin (OPG) and the receptor activator of NF kappa-B ligand (RANKL) in MC3T3-E1 osteoblasts. In the absence of 17β-estradiol, PTH and cAMP enhanced the OPG/RANKL ratio, whereas, OPG/RANKL was suppressed when estradiol was present. In conclusion, our results indicate that the presence of estradiol determines whether PTH and cAMP stimulates or inhibits ERα-dependent activity and the OPG/RANKL mRNA expression in an osteoblastic cell line.
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway. Electronic address: monika.christensen@k2.uib.no.
authors.forename: Monika H E
authors.initials: MH
authors.lastname: Christensen
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Ingvild S
authors.initials: IS
authors.lastname: Fenne
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Marianne H
authors.initials: MH
authors.lastname: Flågeng
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway.
authors.forename: Bjørg
authors.initials: B
authors.lastname: Almås
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Ernst A
authors.initials: EA
authors.lastname: Lien
authors.affiliation: Hormone Laboratory, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D010281:Parathyroid Hormone; D004958:Estradiol
keywords: Estradiol; Estrogen receptor; MC3T3 cells; Osteoblast; PTH; cAMP