| First Author | Farman HH | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 8 | Pages | 3242-52 |
| PubMed ID | 27254004 | Mgi Jnum | J:239760 |
| Mgi Id | MGI:5829612 | Doi | 10.1210/en.2016-1181 |
| Citation | Farman HH, et al. (2016) Female Mice Lacking Estrogen Receptor-alpha in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass. Endocrinology 157(8):3242-52 |
| abstractText | Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)alpha. Central ERalpha exerts an inhibitory role on bone mass. ERalpha is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERalpha in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERalpha expression specifically in POMC neurons (POMC-ERalpha(-/-)). Female POMC-ERalpha(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 mug/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-ERalpha(-/-) 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 ERalpha in VMN is involved in the regulation of bone mass, ERalpha was silenced using an adeno-associated viral vector. Silencing of ERalpha in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERalpha in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERalpha activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERalpha-mediated effects in bone determines cortical bone mass in female mice. |
