title: The role of membrane ERα signaling in bone and other major estrogen responsive tissues.
abstract: Estrogen receptor α (ERα) signaling leads to cellular responses in several tissues and in addition to nuclear ERα-mediated effects, membrane ERα (mERα) signaling may be of importance. To elucidate the significance, in vivo, of mERα signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ERα to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mERα signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40-70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mERα (<35% reduction in estrogen response in NOER mice). In conclusion, mERα signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ERα actions may provide means to develop new selective estrogen receptor modulators with improved profiles.
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: K L
authors.initials: KL
authors.lastname: Gustafsson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Farman
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Henning
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Lionikaite
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Movérare-Skrtic
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Ryberg
authors.affiliation: Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Koskela
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas, 77204-5056, USA.
authors.forename: J-Å
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-90014 Oulu, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Tuukkanen
authors.affiliation: Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California, CA90822, USA.|Department of Developmental and Cell Biology, Department of Medicine, and Department of Biochemistry, University of California, Irvine, California, CA92717, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Levin
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden.
authors.forename: M K
authors.initials: MK
authors.lastname: Lagerquist
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D025461:Feedback, Physiological; D005260:Female; D006811:Humerus / Q000378:metabolism*; D054878:Lipoylation; D008099:Liver / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D010052:Ovariectomy; D015398:Signal Transduction; D013950:Thymus Gland / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D004958:Estradiol