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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. LU ; Egecioglu, E. LU ; Schele, E.; Ryberg, H.; Jansson, J. O.; Tuukkanen, J. and Koskela, A., et al. (2016) In Endocrinology 157(8). p.3242-3252
Abstract

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... (More)

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.

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published
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Endocrinology
volume
157
issue
8
pages
11 pages
publisher
Endocrine Society
external identifiers
  • Scopus:84982832786
ISSN
0013-7227
DOI
10.1210/en.2016-1181
language
English
LU publication?
yes
id
4bbd84cd-7734-4a71-9820-878f645743da
date added to LUP
2016-10-11 08:18:29
date last changed
2016-10-12 03:00:02
@misc{4bbd84cd-7734-4a71-9820-878f645743da,
  abstract     = {<p>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 <sup>-/-</sup> ). Female POMC-ERα <sup>-/-</sup> 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 <sup>-/-</sup> mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P &lt; .01) and mechanical strength (+193 ± 38%, P &lt; .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.</p>},
  author       = {Farman, H. H. and Windahl, S. H. and Westberg, L. and Isaksson, H. and Egecioglu, E. and Schele, E. and Ryberg, H. and Jansson, J. O. and Tuukkanen, J. and Koskela, A. and Xie, S. K. and Hahner, L. and Zehr, J. and Clegg, D. J. and Lagerquist, M. K. and Ohlsson, C.},
  issn         = {0013-7227},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {3242--3252},
  publisher    = {ARRAY(0x8989610)},
  series       = {Endocrinology},
  title        = {Female mice lacking estrogen receptor-α in hypothalamic proopiomelanocortin (POMC) neurons display enhanced estrogenic response on cortical bone mass},
  url          = {http://dx.doi.org/10.1210/en.2016-1181},
  volume       = {157},
  year         = {2016},
}