| First Author | Farman HH | Year | 2017 |
| Journal | J Mol Endocrinol | Volume | 58 |
| Issue | 2 | Pages | 105-111 |
| PubMed ID | 28057769 | Mgi Jnum | J:274508 |
| Mgi Id | MGI:6295272 | Doi | 10.1530/JME-16-0209 |
| Citation | Farman HH, et al. (2017) Extra-nuclear effects of estrogen on cortical bone in males require ERalphaAF-1. J Mol Endocrinol 58(2):105-111 |
| abstractText | Estradiol (E2) signaling via estrogen receptor alpha (ERalpha) is important for the male skeleton as demonstrated by ERalpha inactivation in both mice and man. ERalpha mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERalpha contains various domains, and the role of activation function 1 (ERalphaAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERalphaAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERalphaAF-1-inactivated (ERalphaAF-1(0)) mice were orchidectomized and treated with equimolar doses of 17beta-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERalphaAF-1(0) males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERalphaAF-1(0) mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERalphaAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis. |
