{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T21:23:36Z","timestamp":1787606616834,"version":"build-2736575974"},"reference-count":100,"publisher":"Bioscientifica","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Over recent years, gonadotropins and their receptors have been shown to exert non-traditional actions that bypass the classical hypothalamic\u2013pituitary\u2013gonadal axis. Findings of the expression of receptors for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in skeletal, fat, and immune cells and in neurons suggest that their functions are much broader than their classical roles. FSH, once believed solely to regulate procreation\u2013gonadal development and maturation at puberty and gamete production during the fertile phase, has been found to regulate body composition, bone metabolism, and cognition, providing the underpinnings of complex integrative physiology, and, in turn, opening potential new therapeutic opportunities. Pre-clinical evidence from genetic and pharmacologic interventions in rodent models and human data from population-based observations, genetic studies, and a small number of interventional studies together support the independent skeletal, adipogenic, and cognitive actions of gonadotropins. Here, we review our current understanding of direct actions of FSH and LH on bone, adipose tissue, and brain and focus specifically on the detrimental health burden during and after the menopause: osteoporosis, obesity, and dementia.<\/jats:p>","DOI":"10.1530\/ec-26-0232","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:59:32Z","timestamp":1785337172000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":0,"title":["The extragonadal biology of gonadotropin hormones: should we rename these?"],"prefix":"10.1530","volume":"15","author":[{"given":"Se-Min","family":"Kim","sequence":"first","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Funda","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]},{"name":"Rutgers Health, Jersey City Medical Center 2 , , ,","place":["Jersey City, New Jersey, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorang","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Englewood Hospital and Medical Center 3 , , ,","place":["Englewood, New Jersey, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazilet","family":"Sen","sequence":"additional","affiliation":[{"name":"Turkish Medicines and Medical Devices Agency 4 , ,","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1636-084X","authenticated-orcid":true,"given":"Steven L","family":"Sims","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Gimenez-Roig","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uliana","family":"Cheliadinova","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Vasilyeva","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Barak","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Hutchison","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Macdonald","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rauf","family":"Latif","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki","family":"Goosens","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Frolinger","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Pallapati","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Rojekar","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Ryu","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Lizneva","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Yuen","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5911-9522","authenticated-orcid":true,"given":"Mone","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai 1 , , ,","place":["New York, New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"2026082416564834800_bib1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1530\/rep.1.00660","article-title":"What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?","volume":"130","author":"Kumar","year":"2005","journal-title":"Reproduction"},{"key":"2026082416564834800_bib2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1210\/edrv.21.5.0409","article-title":"Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function","volume":"21","author":"Themmen","year":"2000","journal-title":"Endocr Rev"},{"key":"2026082416564834800_bib3","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S1472-6483(10)62135-9","article-title":"FSH isoform composition of commercial gonadotrophin preparations: a neglected aspect?","volume":"9","author":"Andersen","year":"2004","journal-title":"Reprod Biomed Online"},{"key":"2026082416564834800_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0137897","article-title":"Glycosylation effects on FSH-FSHR interaction dynamics: a case study of different FSH glycoforms by molecular dynamics simulations","volume":"10","author":"Meher","year":"2015","journal-title":"PLoS One"},{"key":"2026082416564834800_bib5","first-page":"23","article-title":"The gonadotropin genes: evolution of distinct mechanisms for hormonal control","volume":"51","author":"Albanese","year":"1996","journal-title":"Recent Prog Horm Res"},{"key":"2026082416564834800_bib6","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1126\/science.100883","article-title":"Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone","volume":"202","author":"Belchetz","year":"1978","journal-title":"Science"},{"key":"2026082416564834800_bib7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.yfrne.2008.07.001","article-title":"Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor","volume":"30","author":"Naor","year":"2009","journal-title":"Front Neuroendocrinol"},{"key":"2026082416564834800_bib8","article-title":"Pituitary Physiology and Diagnostic Evaluation","volume-title":"Williams Textbook of Endocrinology","author":"Kaiser","year":"2025"},{"key":"2026082416564834800_bib9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1210\/edrv-9-2-267","article-title":"Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone","volume":"9","author":"Ying","year":"1988","journal-title":"Endocr Rev"},{"key":"2026082416564834800_bib10","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1210\/en.2005-1282","article-title":"Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion","volume":"147","author":"Dungan","year":"2006","journal-title":"Endocrinology"},{"key":"2026082416564834800_bib11","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.714177","article-title":"Human chorionic gonadotropin and related peptides: candidate anti-inflammatory therapy in early stages of sepsis","volume":"12","author":"Yoo","year":"2021","journal-title":"Front Immunol"},{"key":"2026082416564834800_bib12","doi-asserted-by":"crossref","first-page":"E818","DOI":"10.1152\/classicessays.00006.2004","article-title":"Discovery of the luteinizing hormone of the anterior pituitary gland","volume":"287","author":"Goodman","year":"2004","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2026082416564834800_bib13","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1172\/JCI41350","article-title":"The ovary: basic biology and clinical implications","volume":"120","author":"Richards","year":"2010","journal-title":"J Clin Investig"},{"key":"2026082416564834800_bib14","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1210\/edrv.22.6.0446","article-title":"The functional significance of FSH in spermatogenesis and the control of its secretion in male primates","volume":"22","author":"Plant","year":"2001","journal-title":"Endocr Rev"},{"key":"2026082416564834800_bib15","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41586-022-04463-0","article-title":"FSH blockade improves cognition in mice with Alzheimer\u2019s disease","volume":"603","author":"Xiong","year":"2022","journal-title":"Nature"},{"key":"2026082416564834800_bib16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature22342","article-title":"Blocking FSH induces thermogenic adipose tissue and reduces body fat","volume":"546","author":"Liu","year":"2017","journal-title":"Nature"},{"key":"2026082416564834800_bib17","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1073\/pnas.1718144115","article-title":"Epitope-specific monoclonal antibodies to FSH beta increase bone mass","volume":"115","author":"Ji","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416564834800_bib18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1749-6632.2011.06287.x","article-title":"Skeletal receptors for steroid-family regulating glycoprotein hormones: a multilevel, integrated physiological control system","volume":"1240","author":"Blair","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"2026082416564834800_bib19","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bbrc.2010.02.112","article-title":"FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts","volume":"394","author":"Robinson","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"2026082416564834800_bib20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.cyto.2010.11.011","article-title":"Follicle-stimulating hormone promotes RANK expression on human monocytes","volume":"53","author":"Cannon","year":"2011","journal-title":"Cytokine"},{"key":"2026082416564834800_bib21","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3389\/fendo.2018.00707","article-title":"Structure-function relationships of the follicle-stimulating hormone receptor","volume":"9","author":"Ulloa-Aguirre","year":"2018","journal-title":"Front Endocrinol"},{"key":"2026082416564834800_bib22","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.bbrc.2012.04.104","article-title":"Blocking FSH action attenuates osteoclastogenesis","volume":"422","author":"Zhu","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"2026082416564834800_bib23","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1095\/biolreprod.114.118562","article-title":"FSH receptor (FSHR) expression in human extragonadal reproductive tissues and the developing placenta, and the impact of its deletion on pregnancy in mice","volume":"91","author":"Stilley","year":"2014","journal-title":"Biol Reprod"},{"key":"2026082416564834800_bib24","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1095\/biolreprod32.4.872","article-title":"Biochemical consequences of follicle-stimulating hormone binding to testicular macrophages in culture","volume":"32","author":"Yee","year":"1985","journal-title":"Biol Reprod"},{"key":"2026082416564834800_bib25","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1056\/NEJMoa1001283","article-title":"Expression of follicle-stimulating hormone receptor in tumor blood vessels","volume":"363","author":"Radu","year":"2010","journal-title":"N Engl J Med"},{"key":"2026082416564834800_bib26","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1210\/jc.2002-020777","article-title":"Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status","volume":"88","author":"Randolph","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00198-002-1329-4","article-title":"Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN","volume":"14","author":"Sowers","year":"2003","journal-title":"Osteoporos Int"},{"key":"2026082416564834800_bib28","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cca.2008.09.027","article-title":"Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women","volume":"400","author":"Xu","year":"2009","journal-title":"Clin Chim Acta"},{"key":"2026082416564834800_bib29","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00198-009-0943-9","article-title":"Age-related changes in biochemical markers of bone turnover and gonadotropin levels and their relationship among Chinese adult women","volume":"21","author":"Wu","year":"2010","journal-title":"Osteoporos Int"},{"key":"2026082416564834800_bib30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.maturitas.2011.01.010","article-title":"Bone loss during menopausal transition among southern Chinese women","volume":"69","author":"Cheung","year":"2011","journal-title":"Maturitas"},{"key":"2026082416564834800_bib31","first-page":"2417","article-title":"Correlation analysis for follicle-stimulating hormone and C-terminal cross-linked telopetides of type i collagen in menopausal transition women with osteoporosis","volume":"8","author":"Wang","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"2026082416564834800_bib32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00223-008-9126-5","article-title":"Determinants of bone turnover markers in healthy premenopausal women","volume":"82","author":"Adami","year":"2008","journal-title":"Calcif Tissue Int"},{"key":"2026082416564834800_bib33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.envres.2009.09.012","article-title":"Cadmium, follicle-stimulating hormone, and effects on bone in women age 42\u201360 years, NHANES III","volume":"110","author":"Gallagher","year":"2010","journal-title":"Environ Res"},{"key":"2026082416564834800_bib34","doi-asserted-by":"crossref","first-page":"e1156","DOI":"10.1210\/clinem\/dgaa922","article-title":"Serum FSH is associated with BMD, bone marrow adiposity, and body composition in the AGES-Reykjavik study of older adults","volume":"106","author":"Veldhuis-Vlug","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib35","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s00774-004-0495-1","article-title":"Hypergonadotropic amenorrhea and bone density: new approach to an old problem","volume":"22","author":"Devleta","year":"2004","journal-title":"J Bone Miner Metab"},{"key":"2026082416564834800_bib36","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bone.2015.07.021","article-title":"Mechanisms of enhanced osteoclastogenesis in girls and young women with Turner\u2019s syndrome","volume":"81","author":"Faienza","year":"2015","journal-title":"Bone"},{"key":"2026082416564834800_bib37","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1507\/endocrj.EJ23-0628","article-title":"Factors associated with low bone mineral density in Turner syndrome: a multicenter prospective observational study","volume":"71","author":"Ikegawa","year":"2024","journal-title":"Endocr J"},{"key":"2026082416564834800_bib38","doi-asserted-by":"crossref","first-page":"5063","DOI":"10.1210\/jc.2010-1103","article-title":"Effects of suppression of follicle-stimulating hormone secretion on bone resorption markers in postmenopausal women","volume":"95","author":"Drake","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib39","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1530\/EJE-10-0043","article-title":"FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women","volume":"163","author":"Rendina","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"2026082416564834800_bib40","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3109\/13697137.2012.656160","article-title":"Estrogen-related genes and postmenopausal osteoporosis risk","volume":"15","author":"Mendoza","year":"2012","journal-title":"Climacteric"},{"key":"2026082416564834800_bib41","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cell.2006.01.051","article-title":"FSH directly regulates bone mass","volume":"125","author":"Sun","year":"2006","journal-title":"Cell"},{"key":"2026082416564834800_bib42","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1039\/C6SC04897H","article-title":"Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore","volume":"8","author":"Feng","year":"2017","journal-title":"Chem Sci"},{"key":"2026082416564834800_bib43","doi-asserted-by":"crossref","first-page":"14925","DOI":"10.1073\/pnas.0606805103","article-title":"Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblast and osteoclast formation","volume":"103","author":"Iqbal","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416564834800_bib44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0000586","article-title":"Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency","volume":"2","author":"Wu","year":"2007","journal-title":"PLoS One"},{"key":"2026082416564834800_bib45","doi-asserted-by":"crossref","first-page":"14574","DOI":"10.1073\/pnas.1212806109","article-title":"Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis","volume":"109","author":"Zhu","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416564834800_bib46","doi-asserted-by":"crossref","first-page":"28971","DOI":"10.1073\/pnas.2014588117","article-title":"First-in-class humanized FSH blocking antibody targets bone and fat","volume":"117","author":"Gera","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416564834800_bib47","doi-asserted-by":"crossref","first-page":"22629","DOI":"10.1073\/pnas.1012141108","article-title":"Follicle-stimulating hormone increases bone mass in female mice","volume":"107","author":"Allan","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416564834800_bib48","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00223-008-9134-5","article-title":"Follicle-stimulating hormone does not impact male bone mass in vivo or human male osteoclasts in vitro","volume":"82","author":"Ritter","year":"2008","journal-title":"Calcif Tissue Int"},{"key":"2026082416564834800_bib49","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1210\/en.2006-1404","article-title":"Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone","volume":"148","author":"Gao","year":"2007","journal-title":"Endocrinology"},{"key":"2026082416564834800_bib50","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2006.12.002","article-title":"Sex steroids, not FSH, influence bone mass","volume":"127","author":"Seibel","year":"2006","journal-title":"Cell"},{"key":"2026082416564834800_bib51","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00223-011-9565-2","article-title":"Decreased bone mineral density in rats rendered follicle-deplete by an ovotoxic chemical correlates with changes in follicle-stimulating hormone and inhibin A","volume":"90","author":"Lukefahr","year":"2012","journal-title":"Calcif Tissue Int"},{"key":"2026082416564834800_bib52","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1210\/jc.2006-1393","article-title":"Changes in body composition in women over six years at midlife: ovarian and chronological aging","volume":"92","author":"Sowers","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib53","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1210\/jc.2003-031183","article-title":"Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age","volume":"89","author":"Randolph","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib54","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/acel.12331","article-title":"FSH regulates fat accumulation and redistribution in aging through the Galphai\/Ca(2+)\/CREB pathway","volume":"14","author":"Liu","year":"2015","journal-title":"Aging Cell"},{"key":"2026082416564834800_bib55","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/bju.14609","article-title":"Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study","volume":"123","author":"Ostergren","year":"2019","journal-title":"BJU Int"},{"key":"2026082416564834800_bib56","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cmet.2017.07.018","article-title":"Burning fat and building bone by FSH blockade","volume":"26","author":"Sponton","year":"2017","journal-title":"Cell Metab"},{"key":"2026082416564834800_bib57","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1194\/jlr.M025403","article-title":"FSH stimulates lipid biosynthesis in chicken adipose tissue by upregulating the expression of its receptor FSHR","volume":"53","author":"Cui","year":"2012","journal-title":"J Lipid Res"},{"key":"2026082416564834800_bib58","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.theriogenology.2020.10.029","article-title":"FSH promotes fat accumulation by activating PPARgamma signaling in surgically castrated, but not immunocastrated, male pigs","volume":"160","author":"Han","year":"2021","journal-title":"Theriogenology"},{"key":"2026082416564834800_bib59","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.139160","article-title":"\u03b23-Adrenergic receptors regulate human brown\/beige adipocyte lipolysis and thermogenesis","volume":"6","author":"Cero","year":"2021","journal-title":"JCI Insight"},{"key":"2026082416564834800_bib60","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.neurobiolaging.2018.04.004","article-title":"Sexual dimorphism in predisposition to Alzheimer\u2019s disease","volume":"70","author":"Fisher","year":"2018","journal-title":"Neurobiol Aging"},{"key":"2026082416564834800_bib61","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5498\/wjp.v6.i1.54","article-title":"Sex differences in cognitive impairment in Alzheimer\u2019s disease","volume":"6","author":"Laws","year":"2016","journal-title":"World J Psychiatry"},{"key":"2026082416564834800_bib62","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11682-016-9523-8","article-title":"Sex differences in the association between AD biomarkers and cognitive decline","volume":"11","author":"Koran","year":"2017","journal-title":"Brain Imaging Behav"},{"key":"2026082416564834800_bib63","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1212\/WNL.48.6.1511","article-title":"The Alzheimer\u2019s disease assessment scale: patterns and predictors of baseline cognitive performance in multicenter Alzheimer\u2019s disease trials","volume":"48","author":"Doraiswamy","year":"1997","journal-title":"Neurology"},{"key":"2026082416564834800_bib64","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1212\/WNL.57.4.605","article-title":"High-dose estradiol improves cognition for women with AD: results of a randomized study","volume":"57","author":"Asthana","year":"2001","journal-title":"Neurology"},{"key":"2026082416564834800_bib65","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1001\/jama.283.8.1007","article-title":"Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer\u2019s disease cooperative study","volume":"283","author":"Mulnard","year":"2000","journal-title":"JAMA"},{"key":"2026082416564834800_bib66","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1001\/jama.288.17.2123","article-title":"Hormone replacement therapy and incidence of Alzheimer disease in older women: the cache county study","volume":"288","author":"Zandi","year":"2002","journal-title":"JAMA"},{"key":"2026082416564834800_bib67","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1001\/jama.291.24.2947","article-title":"Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: women\u2019s health initiative memory study","volume":"291","author":"Shumaker","year":"2004","journal-title":"JAMA"},{"key":"2026082416564834800_bib68","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1001\/jama.291.24.2959","article-title":"Conjugated equine estrogens and global cognitive function in postmenopausal women: women\u2019s health initiative memory study","volume":"291","author":"Espeland","year":"2004","journal-title":"JAMA"},{"key":"2026082416564834800_bib69","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0167-4943(96)00764-9","article-title":"Gonadotropin, ACTH, prolactin, sexual steroid and cortisol levels in postmenopausal women\u2019s cerebrospinal fluid (CSF)","volume":"24","author":"Molnar","year":"1997","journal-title":"Arch Gerontol Geriatr"},{"key":"2026082416564834800_bib70","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/S0025-6196(11)62109-5","article-title":"Elevated gonadotropin levels in patients with Alzheimer disease","volume":"76","author":"Short","year":"2001","journal-title":"Mayo Clin Proc"},{"key":"2026082416564834800_bib71","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1210\/jc.2013-1808","article-title":"Menopause effects on verbal memory: findings from a longitudinal community cohort","volume":"98","author":"Epperson","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib72","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1001\/jama.2020.1757","article-title":"The menopause transition and cognition","volume":"323","author":"Greendale","year":"2020","journal-title":"JAMA"},{"key":"2026082416564834800_bib73","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1212\/WNL.0b013e3181a71193","article-title":"Effects of the menopause transition and hormone use on cognitive performance in midlife women","volume":"72","author":"Greendale","year":"2009","journal-title":"Neurology"},{"key":"2026082416564834800_bib74","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1093\/aje\/kwq067","article-title":"Menopause-associated symptoms and cognitive performance: results from the study of women\u2019s health across the nation","volume":"171","author":"Greendale","year":"2010","journal-title":"Am J Epidemiol"},{"key":"2026082416564834800_bib75","doi-asserted-by":"crossref","DOI":"10.3389\/frdem.2023.1303256","article-title":"Elevated gonadotropin levels are associated with increased biomarker risk of Alzheimer\u2019s disease in midlife women","volume":"2","author":"Nerattini","year":"2023","journal-title":"Front Dement"},{"key":"2026082416564834800_bib76","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000330472","article-title":"Influence of variation in the follicle-stimulating hormone receptor gene (FSHR) and age at menopause on the development of Alzheimer\u2019s disease in women","volume":"32","author":"Corbo","year":"2011","journal-title":"Dement Geriatr Cogn Disord"},{"key":"2026082416564834800_bib77","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.79612","article-title":"Brain atlas for glycoprotein hormone receptors at single-transcript level","volume":"11","author":"Ryu","year":"2022","journal-title":"Elife"},{"key":"2026082416564834800_bib78","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1210\/endo.132.5.8477671","article-title":"Novel expression of human chorionic gonadotropin\/luteinizing hormone receptor gene in brain","volume":"132","author":"Lei","year":"1993","journal-title":"Endocrinology"},{"key":"2026082416564834800_bib79","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1038\/s41380-024-02824-x","article-title":"Gene\u2013dose-dependent reduction of Fshr expression improves spatial memory deficits in Alzheimer\u2019s mice","volume":"30","author":"Korkmaz","year":"2025","journal-title":"Mol Psychiatry"},{"key":"2026082416564834800_bib80","doi-asserted-by":"crossref","first-page":"6577","DOI":"10.1038\/s41467-023-42282-7","article-title":"FSH and ApoE4 contribute to Alzheimer\u2019s disease-like pathogenesis via C\/EBPbeta\/delta-secretase in female mice","volume":"14","author":"Xiong","year":"2023","journal-title":"Nat Commun"},{"key":"2026082416564834800_bib81","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1055\/s-2001-13906","article-title":"An overview of the past, present, and future of nongonadal LH\/hCG actions in reproductive biology and medicine","volume":"19","author":"Rao","year":"2001","journal-title":"Semin Reprod Med"},{"key":"2026082416564834800_bib82","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1210\/jcem-70-2-421","article-title":"The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes, and decidua","volume":"70","author":"Reshef","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib83","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1210\/jc.2002-021966","article-title":"Human cervix contains functional luteinizing hormone\/human chorionic gonadotropin receptors","volume":"88","author":"Lin","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib84","first-page":"1188","article-title":"Lack of self-regulation of human chorionic gonadotropin biosynthesis in human choriocarcinoma cells","volume":"78","author":"Licht","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib85","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1210\/endo.132.3.7679981","article-title":"Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts","volume":"132","author":"Shi","year":"1993","journal-title":"Endocrinology"},{"key":"2026082416564834800_bib86","first-page":"2397","article-title":"Novel presence of luteinizing hormone\/chorionic gonadotropin receptors in human adrenal glands","volume":"81","author":"Pabon","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2026082416564834800_bib87","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0006-8993(94)90478-2","article-title":"Administration of human chorionic gonadotropin affects sleep-wake phases and other associated behaviors in cycling female rats","volume":"654","author":"Toth","year":"1994","journal-title":"Brain Res"},{"key":"2026082416564834800_bib88","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1006\/hbeh.1995.1004","article-title":"Peripheral and intracerebroventricular administration of human chorionic gonadotropin alters several hippocampus-associated behaviors in cycling female rats","volume":"29","author":"Lukacs","year":"1995","journal-title":"Horm Behav"},{"key":"2026082416564834800_bib89","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1046\/j.1365-2826.2000.00461.x","article-title":"An association of elevated serum gonadotropin concentrations and Alzheimer disease?","volume":"12","author":"Bowen","year":"2000","journal-title":"J Neuroendocrinol"},{"key":"2026082416564834800_bib90","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3121\/cmr.2007.741","article-title":"The contribution of luteinizing hormone to Alzheimer disease pathogenesis","volume":"5","author":"Webber","year":"2007","journal-title":"Clin Med Res"},{"key":"2026082416564834800_bib91","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1677\/JOE-06-0101","article-title":"In vitro effects of chorionic gonadotropin hormone on human adipose development","volume":"194","author":"Dos Santos","year":"2007","journal-title":"J Endocrinol"},{"key":"2026082416564834800_bib92","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/BF01575502","article-title":"Controversies in plastic surgery: suction-assisted lipectomy (SAL) and the hCG (human chorionic gonadotropin) protocol for obesity treatment","volume":"11","author":"Vogt","year":"1987","journal-title":"Aesthetic Plast Surg"},{"key":"2026082416564834800_bib93","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1365-2125.1995.tb05779.x","article-title":"The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis","volume":"40","author":"Lijesen","year":"1995","journal-title":"Br J Clin Pharmacol"},{"key":"2026082416564834800_bib94","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.1210\/en.2003-0036","article-title":"Luteinizing hormone receptor knockout (LuRKO) mice and transgenic human chorionic gonadotropin (hCG)-overexpressing mice (hCG alphabeta+) have bone phenotypes","volume":"144","author":"Yarram","year":"2003","journal-title":"Endocrinology"},{"key":"2026082416564834800_bib95","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.mce.2006.10.019","article-title":"Extragonadal LH\/hCG action \u2013 not yet time to rewrite textbooks","volume":"269","author":"Pakarainen","year":"2007","journal-title":"Mol Cell Endocrinol"},{"key":"2026082416564834800_bib96","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.theriogenology.2020.03.005","article-title":"A novel follicle-stimulating hormone vaccine for controlling fat accumulation","volume":"148","author":"Han","year":"2020","journal-title":"Theriogenology"},{"key":"2026082416564834800_bib97","doi-asserted-by":"crossref","DOI":"10.1172\/JCI182702","article-title":"Efficacy and safety of a therapeutic humanized FSH-blocking antibody in obesity and Alzheimer\u2019s disease models","volume":"135","author":"Pallapati","year":"2025","journal-title":"J Clin Investig"},{"key":"2026082416564834800_bib98","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.78022","article-title":"FSH-blocking therapeutic for osteoporosis","volume":"11","author":"Gera","year":"2022","journal-title":"Elife"},{"key":"2026082416564834800_bib99","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.88898","article-title":"Development and biophysical characterization of a humanized FSH-blocking monoclonal antibody therapeutic formulated at an ultra-high concentration","volume":"12","author":"Rojekar","year":"2023","journal-title":"Elife"},{"key":"2026082416564834800_bib100","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/nyas.14952","article-title":"Optimizing a therapeutic humanized follicle-stimulating hormone-blocking antibody formulation by protein thermal shift assay","volume":"1521","author":"Sant","year":"2023","journal-title":"Ann N Y Acad Sci"}],"container-title":["Endocrine Connections"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0232\/522913\/ec-26-0232.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-26-0232\/522913\/ec-26-0232.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:57:03Z","timestamp":1787605023000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article\/15\/8\/e260232\/77914\/The-extragonadal-biology-of-gonadotropin-hormones"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":100,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1530\/ec-26-0232","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"article-number":"e260232"}}