{"entity": "publication", "iuid": "7bdd2bcdaec14360a6b92d1c49b4dc63", "timestamp": "2026-10-18T23:03:16.072Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7bdd2bcdaec14360a6b92d1c49b4dc63.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7bdd2bcdaec14360a6b92d1c49b4dc63"}}, "title": "Membrane-initiated estrogen receptor-\u03b1 signaling in the hypothalamus regulates trabecular bone in femur in female mice.", "authors": [{"family": "Jiang", "given": "Yiwen", "initials": "Y"}, {"family": "Horkeby", "given": "Karin", "initials": "K", "orcid": "0000-0003-2082-4886", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6412d4867264f95a0f56cf6a819498a.json"}}, {"family": "Henning", "given": "Petra", "initials": "P"}, {"family": "Nilsson", "given": "Karin H", "initials": "KH"}, {"family": "Wu", "given": "Jianyao", "initials": "J"}, {"family": "Li", "given": "Lei", "initials": "L"}, {"family": "Mov\u00e9rare-Skrtic", "given": "Sofia", "initials": "S"}, {"family": "Ohlsson", "given": "Claes", "initials": "C"}, {"family": "Lagerquist", "given": "Marie K", "initials": "MK"}], "type": "journal article", "published": "2026-05-01", "journal": {"title": "J Endocrinol", "issn": "1479-6805", "volume": "269", "issue": "2", "issn-l": null}, "abstract": "Membrane-initiated estrogen receptor-\u03b1 (mER\u03b1) signaling has been demonstrated to be crucial for normal bone metabolism, and our previous work has confirmed its essential role in osteoblasts. However, the contribution of brain-derived mER\u03b1 signaling to bone homeostasis remains unexplored. To investigate the role of brain-derived mER\u03b1 signaling in bone metabolism, we developed a POMC-C451Af/f mouse model in which mER\u03b1 signaling is selectively inactivated in POMC-expressing neurons. Gonadal-intact female POMC-C451Af/f mice exhibited disturbed sex steroid levels and significantly increased bone mass in both cortical and trabecular compartments compared to littermate C451Af/f controls after sexual maturation (16 weeks old). In ovariectomized female POMC-C451Af/f mice, estradiol (E2) treatment enhanced the anabolic response in trabecular bone of the femur compared to controls, while the estrogen response in cortical bone was similar between the genotypes. Gonadal-intact male POMC-C451Af/f mice displayed altered levels of testosterone compared to controls at 24 weeks of age. In orchiectomized male mice, responses to E2 treatment were similar across all examined parameters between POMC-C451Af/f and control mice. In conclusion, our findings reveal an important role of membrane-initiated ER\u03b1 signaling in POMC neurons in regulating hormone balance and bone metabolism, with more pronounced effects in female mice.", "doi": "10.1530/JOE-25-0462", "pmid": "42133461", "labels": {"Clinical Genomics Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13192689"}, {"db": "pii", "key": "JOE-25-0462"}], "notes": [], "created": "2026-10-16T15:04:53.856Z", "modified": "2026-10-16T15:04:53.867Z"}