Mice lacking estrogen receptor [alpha] in hypothalamic POMC neurons display enhanced estrogenic response on cortical bone mass

2016 ◽  
Author(s):  
Helen Farman ◽  
Sara Windahl ◽  
Deborah Clegg ◽  
Shang Kui Xie ◽  
Lars Westberg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Cortical Bone ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Cortical Bone Mass

scholarly journals Female Mice Lacking Estrogen Receptor-Alpha in Osteoblasts Have Compromised Bone Mass and Strength

2014 ◽  
Vol 29 (2) ◽  
pp. 370-379 ◽  
Author(s):  
Katherine M Melville ◽  
Natalie H Kelly ◽  
Sohaib A Khan ◽  
John C Schimenti ◽  
F Patrick Ross ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Female Mice

scholarly journals Estrogen receptor‐alpha genotype affects exercise‐related bone mass in young healthy women

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Hiroyo Kondo ◽  
Hidemi Fujino ◽  
Shinichiro Murakami ◽  
Naoto Fujita ◽  
Fumiko Nagatomo ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Healthy Women

scholarly journals Vitamin D receptor and Estrogen receptor alpha Genotype affects Exercise related Bone mass in Japanese healthy women

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Hiroyo Kondo ◽  
Hidemi Fujino ◽  
Shinichiro Murakami ◽  
Naoto Fujita ◽  
Fumiko Nagatomo ◽  
...  
Keyword(s):  
Vitamin D ◽  
Estrogen Receptor ◽  
Bone Mass ◽  
Vitamin D Receptor ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Healthy Women

scholarly journals Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3242-3252 ◽  
Author(s):  
H. H. Farman ◽  
S. H. Windahl ◽  
L. Westberg ◽  
H. Isaksson ◽  
E. Egecioglu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Mechanical Strength ◽  
Cortical Bone ◽  
Volume Fraction ◽  
Bone Thickness ◽  
Female Mice ◽  
Cortical Bone Thickness ◽  
Cortical Bone Mass ◽  
Estrogenic Responses

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.

Arginine site 264 in murine estrogen receptor alpha is dispensable for the regulation of the skeleton

2020 ◽  
Author(s):  
Karin L. Gustafsson ◽  
Helen H. Farman ◽  
Karin H. Nilsson ◽  
Petra Henning ◽  
Sofia Movérare-Skrtic ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Thickness ◽  
Intracellular Signaling ◽  
Estrogen Receptor Alpha ◽  
Estrogen Treatment ◽  
Receptor Alpha ◽  
Trabecular Bone Mass

Estrogen protects against bone loss, but is not a suitable treatment due to adverse effects in other tissues. Increased knowledge regarding estrogen signaling in estrogen-responsive tissues is therefore warranted to aid the development of bone-specific estrogen treatments. Estrogen receptor alpha (ERα), the main mediator of estrogenic effects in bone, is widely subjected to posttranslational modifications (PTMs). In vitro studies have shown that methylation at site R260 in the human ERα affects receptor localization and intracellular signaling. The corresponding amino acid R264 in murine ERα has been shown to have a functional role in endothelium in vivo; albeit the methylation of R264 in the murine gene is yet to be empirically demonstrated. The aim of this study was to investigate if R264 in ERα is involved in the regulation of the skeleton in vivo. DXA analysis at three, six, nine, and twelve months of age showed no differences in total body areal BMD between R264A and WT in either female or male mice. Furthermore, analyses using CT demonstrated that trabecular bone mass in tibia and vertebra, and cortical thickness in tibia, were similar between R264A and WT mice. In addition, R264A females displayed a normal estrogen treatment response in trabecular bone mass, as well as in cortical thickness. Furthermore, uterus, thymus, and adipose tissue responded similarly in R264A and WT female mice after estrogen treatment. In conclusion, our novel finding that mutation of R264 in ERα does not affect the regulation of the skeleton, together with the known role of R264 for ERα-mediated endothelial effects, supports the concept that R264 determines tissue specificity of ERα.

scholarly journals Testosterone and the Male Skeleton: A Dual Mode of Action

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Mieke Sinnesael ◽  
Steven Boonen ◽  
Frank Claessens ◽  
Evelien Gielen ◽  
Dirk Vanderschueren
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Bone Mass ◽  
Bone Turnover ◽  
Mode Of Action ◽  
Estrogen Receptor Alpha ◽  
Receptor Activation ◽  
Male Mice ◽  
Dual Mode ◽  
Receptor Alpha

Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor.

scholarly journals Deletion of Estrogen Receptor Beta in Osteoprogenitor Cells Increases Trabecular but Not Cortical Bone Mass in Female Mice

2015 ◽  
Vol 31 (3) ◽  
pp. 606-614 ◽  
Author(s):  
Kristy M Nicks ◽  
Koji Fujita ◽  
Daniel Fraser ◽  
Ulrike McGregor ◽  
Matthew T Drake ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Cortical Bone ◽  
Estrogen Receptor Beta ◽  
Osteoprogenitor Cells ◽  
Female Mice ◽  
Cortical Bone Mass ◽  
Receptor Beta

scholarly journals Interaction of the effects between estrogen receptor‐alpha polymorphism and physical activity or nutrient on bone mass in Japanese young women

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Hiroyo Kondo ◽  
Hidemi Fujino ◽  
Shinichiro Murakami ◽  
Isao Takeda ◽  
Akihiko Ishihara
Keyword(s):  
Physical Activity ◽  
Estrogen Receptor ◽  
Bone Mass ◽  
Young Women ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha
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