Membrane-initiated estrogen receptor-α signaling in the hypothalamus regulates trabecular bone in femur in female mice.

Overview

Authors: Yiwen Jiang¹, Karin Horkeby¹, Petra Henning¹, Karin H Nilsson¹, Jianyao Wu¹, Lei Li¹, Sofia Movérare-Skrtic¹, Claes Ohlsson^1,2, Marie K Lagerquist¹

ORCID iDs: Karin Horkeby

Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Drug Treatment, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden

Journal: The Journal of endocrinology, volume 269, issue 2, article e250462

Dates: received 4 December 2025; accepted 4 May 2026; published online 20 May 2026; in print 1 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1530/joe-25-0462 · PMID 42133461 · PMCID PMC13192689 · OpenAlex W7161197002

Open access: hybrid, a free copy (OpenAlex)

Status: data only

Categories: mouse (organism), cellular / molecular (subfield)

Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, fMRI & imaging

Keywords: estrogen receptor alpha, estrogenic effects, osteoporosis, bone tissue, central nervous system, neurons

MeSH: Cancellous Bone*, Estrogen Receptor alpha*, Femur*, Hypothalamus*, Signal Transduction*, Animals, Estradiol, Female, Male, Mice, Neurons, Ovariectomy, Pro-Opiomelanocortin (* major topic)

Topic: Menopause: Health Impacts and Treatments (Endocrinology, Diabetes and Metabolism, Medicine), according to OpenAlex

Funding: Novo Nordisk (26844); Vetenskapsrådet (2020-01840, FAI-2018-0466, 2018); Sahlgrenska Universitetssjukhuset; Göteborgs Universitet; Science for Life Laboratory

Citations: not cited yet (Europe PMC); 53 references in the paper

Abstract

Membrane-initiated estrogen receptor-α (mERα) 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 mERα signaling to bone homeostasis remains unexplored. To investigate the role of brain-derived mERα signaling in bone metabolism, we developed a POMC-C451Af/f mouse model in which mERα 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 ERα signaling in POMC neurons in regulating hormone balance and bone metabolism, with more pronounced effects in female mice.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

geo:GSE328990 — at NCBI GEO; found in “Data availability”

Data availability

The data supporting the results of this study are available on request from the corresponding author. RNA-seq data, including raw data files (fastq format) and processed data files (matrix table of gene counts and differentially expressed genes in CSV format), are available in the Gene Expression Omnibus (GEO) repository, accession number GSE328990 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328990).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

Publisher: — → Bioscientifica
Funding: added Novo Nordisk: 26844; Vetenskapsrådet: 2020-01840, FAI-2018-0466, 2018; Sahlgrenska Universitetssjukhuset; Göteborgs Universitet; Science for Life Laboratory

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 6 keywords, 13 MeSH terms, 52 references.

Cite

This paper

Jiang, Y., Horkeby, K., Henning, P., Nilsson, K. H., Wu, J., Li, L., Movérare-Skrtic, S., Ohlsson, C., & Lagerquist, M. K. (2026). Membrane-initiated estrogen receptor-α signaling in the hypothalamus regulates trabecular bone in femur in female mice. The Journal of endocrinology, 269(2), e250462. https://doi.org/10.1530/joe-25-0462

BibTeX

@article{jiang2026membrane, author = {Jiang, Yiwen and Horkeby, Karin and Henning, Petra and Nilsson, Karin H and Wu, Jianyao and Li, Lei and Movérare-Skrtic, Sofia and Ohlsson, Claes and Lagerquist, Marie K}, title = {{Membrane-initiated estrogen receptor-α signaling in the hypothalamus regulates trabecular bone in femur in female mice}}, journal = {The Journal of endocrinology}, year = {2026}, month = may, volume = {269}, number = {2}, pages = {e250462}, publisher = {Bioscientifica}, issn = {0022-0795}, doi = {10.1530/joe-25-0462}, url = {https://doi.org/10.1530/joe-25-0462}, pmid = {42133461}, pmcid = {PMC13192689} }

RIS

TY - JOUR AU - Jiang, Yiwen AU - Horkeby, Karin AU - Henning, Petra AU - Nilsson, Karin H AU - Wu, Jianyao AU - Li, Lei AU - Movérare-Skrtic, Sofia AU - Ohlsson, Claes AU - Lagerquist, Marie K TI - Membrane-initiated estrogen receptor-α signaling in the hypothalamus regulates trabecular bone in femur in female mice T2 - The Journal of endocrinology J2 - J Endocrinol PY - 2026 DA - 2026/05/20 VL - 269 IS - 2 SP - e250462 SN - 0022-0795 PB - Bioscientifica DO - 10.1530/joe-25-0462 UR - https://doi.org/10.1530/joe-25-0462 LA - en ER -

CSL-JSON

{ "id": "10.1530/joe-25-0462", "type": "article-journal", "title": "Membrane-initiated estrogen receptor-α signaling in the hypothalamus regulates trabecular bone in femur in female mice", "container-title": "The Journal of endocrinology", "author": [ { "family": "Jiang", "given": "Yiwen" }, { "family": "Horkeby", "given": "Karin" }, { "family": "Henning", "given": "Petra" }, { "family": "Nilsson", "given": "Karin H" }, { "family": "Wu", "given": "Jianyao" }, { "family": "Li", "given": "Lei" }, { "family": "Movérare-Skrtic", "given": "Sofia" }, { "family": "Ohlsson", "given": "Claes" }, { "family": "Lagerquist", "given": "Marie K" } ], "container-title-short": "J Endocrinol", "volume": "269", "issue": "2", "page": "e250462", "DOI": "10.1530/joe-25-0462", "PMID": "42133461", "PMCID": "PMC13192689", "ISSN": "0022-0795", "publisher": "Bioscientifica", "URL": "https://doi.org/10.1530/joe-25-0462", "language": "en", "issued": { "date-parts": [ [ 2026, 5, 20 ] ] } }

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.