학술논문
Phosphorylation of S122 in ERα is important for the skeletal response to estrogen treatment in male mice.
Document Type
Academic Journal
Author
Horkeby K; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden. karin.horkeby@gu.se.; Farman HH; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Movérare-Skrtic S; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Lionikaite V; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Wu J; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Henning P; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Windahl S; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.; Sjögren K; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Ohlsson C; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.; Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.; Lagerquist MK; Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Klinfarmlab, Vita Stråket 11, 413 45, Göteborg, Sweden.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Subject
Language
English
Abstract
Estrogen receptor alpha (ERα) signaling has beneficial skeletal effects in males. ERα signaling also affects other tissues, and to find bone-specific treatments, more knowledge regarding tissue-specific ERα signaling is needed. ERα is subjected to posttranslational modifications, including phosphorylation, which can influence ERα function in a tissue-specific manner. To determine the importance of phosphorylation site S122 (corresponding to human ERα 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, ERα 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.
(© 2022. The Author(s).)
(© 2022. The Author(s).)