| First Author | Horkeby K | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 22449 |
| PubMed ID | 36575297 | Mgi Jnum | J:334367 |
| Mgi Id | MGI:7413663 | Doi | 10.1038/s41598-022-26939-9 |
| Citation | Horkeby K, et al. (2022) Phosphorylation of S122 in ERalpha is important for the skeletal response to estrogen treatment in male mice. Sci Rep 12(1):22449 |
| abstractText | Estrogen receptor alpha (ERalpha) signaling has beneficial skeletal effects in males. ERalpha signaling also affects other tissues, and to find bone-specific treatments, more knowledge regarding tissue-specific ERalpha signaling is needed. ERalpha is subjected to posttranslational modifications, including phosphorylation, which can influence ERalpha function in a tissue-specific manner. To determine the importance of phosphorylation site S122 (corresponding to human ERalpha site S118) for the skeleton and other tissues, male mice with a S122A mutation were used. Total areal bone mineral density was similar between gonadal intact S122A and WT littermates followed up to 12 months of age, and weights of estrogen-responsive organs normalized for body weight were unchanged between S122A and WT males at both 3 and 12 months of age. Interestingly, 12-month-old S122A males had decreased body weight compared to WT. To investigate if site S122 affects the estrogen response in bone and other tissues, 12-week-old S122A and WT males were orchidectomized (orx) and treated with estradiol (E2) or placebo pellets for four weeks. E2 increased cortical thickness in tibia in both orx WT (+ 60%, p < 0.001) and S122A (+ 45%, p < 0.001) males. However, the E2 effect on cortical thickness was significantly decreased in orx S122A compared to WT mice (- 24%, p < 0.05). In contrast, E2 affected trabecular bone and organ weights similarly in orx S122A and WT males. Thus, ERalpha phosphorylation site S122 is required for a normal E2 response specifically in cortical bone in male mice, a finding that may have implications for development of future treatments against male osteoporosis. |
