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Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.
Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C.
Affiliation
  • Farman HH; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Windahl SH; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Westberg L; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Isaksson H; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Egecioglu E; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Schele E; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Ryberg H; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Jansson JO; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Tuukkanen J; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Koskela A; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Xie SK; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Hahner L; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Zehr J; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Clegg DJ; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Lagerquist MK; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
  • Ohlsson C; Centre for Bone and Arthritis Research (H.H.F., S.H.W., H.R., M.K.L., C.O.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE413 45 Gothenburg, Sweden; Department of Pharmacology (L.W., E.E.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothen
Endocrinology ; 157(8): 3242-52, 2016 08.
Article in En | MEDLINE | ID: mdl-27254004
Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 µg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pro-Opiomelanocortin / Bone Density / Estrogen Receptor alpha / Estrogens / Cortical Bone / Hypothalamus / Neurons Limits: Animals Language: En Journal: Endocrinology Year: 2016 Document type: Article Country of publication: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pro-Opiomelanocortin / Bone Density / Estrogen Receptor alpha / Estrogens / Cortical Bone / Hypothalamus / Neurons Limits: Animals Language: En Journal: Endocrinology Year: 2016 Document type: Article Country of publication: Estados Unidos