{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T21:26:19Z","timestamp":1785878779722,"version":"3.56.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T00:00:00Z","timestamp":1651363200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:p>Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. ERs exert effects via nuclear actions but can also utilize membrane-initiated signaling pathways. To determine if membrane-initiated ER\u03b1 (mER\u03b1) signaling affects SERM action in a tissue-specific manner, C451A mice, lacking mER\u03b1 signaling due to a mutation at palmitoylation site C451, were treated with Lasofoxifene (Las), Bazedoxifene (Bza), or estradiol (E2), and various tissues were evaluated. Las and Bza treatment increased uterine weight to a similar extent in C451A and control mice, demonstrating mER\u03b1-independent uterine SERM effects, while the E2 effect on the uterus was predominantly mER\u03b1-dependent. Las and Bza treatment increased both trabecular and cortical bone mass in controls to a similar degree as E2, while both SERM and E2 treatment effects were absent in C451A mice. This demonstrates that SERM effects, similar to E2 effects, in the skeleton are mER\u03b1-dependent. Both Las and E2 treatment decreased thymus weight in controls, while neither treatment affected the thymus in C451A mice, demonstrating mER\u03b1-dependent SERM and E2 effects in this tissue. Interestingly, both SERM and E2 treatments decreased the total body fat percent in C451A mice, demonstrating the ability of these treatments to affect fat tissue in the absence of functional mER\u03b1 signaling. In conclusion, mER\u03b1 signaling can modulate SERM responses in a tissue-specific manner. This novel knowledge increases the understanding of the mechanisms behind SERM effects and may thereby facilitate the development of new improved SERMs.<\/jats:p>","DOI":"10.1530\/joe-21-0398","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T04:53:57Z","timestamp":1646715237000},"page":"75-84","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":10,"title":["A tissue-specific role of membrane-initiated ER\u03b1 signaling for the effects of SERMs"],"prefix":"10.1530","volume":"253","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-4886","authenticated-orcid":true,"given":"Karin L","family":"Gustafsson","sequence":"first","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Mov\u00e9rare-Skrtic","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen H","family":"Farman","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Engdahl","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"},{"name":"2Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Henning","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin H","family":"Nilsson","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M","family":"Scheffler","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"},{"name":"2Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edina","family":"Sehic","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"},{"name":"2Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"Islander","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"},{"name":"2Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellis","family":"Levin","sequence":"additional","affiliation":[{"name":"3Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, California, USA"},{"name":"4Department of Veterans Affairs Medical Center, Long Beach, Long Beach, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claes","family":"Ohlsson","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"},{"name":"5Department of Drug Treatment, Sahlgrenska University Hospital, Region V\u00e4stra G\u00f6taland, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie K","family":"Lagerquist","sequence":"additional","affiliation":[{"name":"1Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/253\/2\/JOE-21-0398.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/253\/2\/JOE-21-0398.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:38Z","timestamp":1784555858000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/253\/2\/75-84\/5472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,1]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/joe-21-0398","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,1]]}}}