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Female mice lacking estrogen receptor-α in hypothalamic proopiomelanocortin (POMC) neurons display enhanced estrogenic response on cortical bone mass

In English

Författare

  • H. H. Farman
  • S. H. Windahl
  • L. Westberg
  • H. Isaksson
  • E. Egecioglu
  • E. Schele
  • H. Ryberg
  • J. O. Jansson
  • J. Tuukkanen
  • A. Koskela
  • S. K. Xie
  • L. Hahner
  • J. Zehr
  • D. J. Clegg
  • M. K. Lagerquist
  • C. Ohlsson
Visa allt

Summary, in English

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor(ER)α.CentralERα exertsaninhibitoryroleonbonemass.ERα ishighlyexpressedinthearcuate (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 ERaα-mediated effects in bone determines cortical bone mass in female mice.

Publiceringsår

2016-08-01

Språk

Engelska

Sidor

3242-3252

Publikation/Tidskrift/Serie

Endocrinology

Volym

157

Issue

8

Dokumenttyp

Artikel i tidskrift

Förlag

Oxford University Press

Ämne

  • Endocrinology and Diabetes
  • Orthopedics

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 0013-7227