{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:57:16Z","timestamp":1790675836150,"version":"4.1.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005227","name":"Jilin Provincial Department of Health","doi-asserted-by":"publisher","award":["2020SCZT087"],"award-info":[{"award-number":["2020SCZT087"]}],"id":[{"id":"10.13039\/501100005227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Androgenetic alopecia (AGA) is the most prevalent form of non-scarring hair loss, and its pathogenesis is quite complex, involving androgen metabolism, follicular microenvironment imbalance, oxidative stress, and inflammatory responses. Understanding these multifactorial mechanisms is critical for developing effective therapeutic strategies. To this end, various experimental models have been extensively employed. In this review, we summarized recent progress in AGA model research, covering\n                    <jats:italic>in vitro<\/jats:italic>\n                    cell models such as dermal papilla cells and keratinocytes,\n                    <jats:italic>in vivo<\/jats:italic>\n                    animal models\u2014primarily mice treated with testosterone or dihydrotestosterone, as well as genetically modified strains, and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    hair follicle organ culture models. Some emerging approaches, like three-dimensional organoid systems and Organ-on-a-Chip Technologies, are also discussed. The aim of this review is to provide a theoretical framework to guide future drug development and mechanistic studies in AGA.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1935819","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:13:56Z","timestamp":1790673236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in androgenetic alopecia model research"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingrui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biological and Food Engineering, Jilin Engineering Normal University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangchun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5301","DOI":"10.1038\/s41467-018-07579-y","article-title":"Tissue engineering of human hair follicles using a biomimetic developmental approach","volume":"9","author":"Abaci","year":"2018","journal-title":"Nat. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"9909","DOI":"10.4081\/dr.2024.9909","article-title":"Comparison between dutasteride and finasteride in hair regrowth and reversal of miniaturization in male and female androgenetic alopecia: a systematic review","volume":"16","author":"Almudimeegh","year":"2024","journal-title":"Dermatol Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13059-020-1935-5","article-title":"Opportunities and challenges in long-read sequencing data analysis","volume":"21","author":"Amarasinghe","year":"2020","journal-title":"Genome Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/s41423-022-00858-1","article-title":"NADPH oxidase family proteins: signaling dynamics to disease management","volume":"19","author":"Begum","year":"2022","journal-title":"Cell Mol. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1093\/clinchem\/hvaf043","article-title":"MIQE 2.0: revision of the minimum information for publication of quantitative real-time PCR experiments guidelines","volume":"71","author":"Bustin","year":"2025","journal-title":"Clin. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"111096","DOI":"10.1016\/j.mce.2020.111096","article-title":"Androgens downregulate BMP2 impairing the inductive role of dermal papilla cells on hair follicle stem cells differentiation","volume":"520","author":"Ceruti","year":"2021","journal-title":"Mol. Cell Endocrinol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.3389\/fphar.2019.01528","article-title":"Dihydrotestosterone regulates hair growth through the Wnt\/\u03b2-Catenin pathway in C57BL\/6 mice and in vitro organ culture","volume":"10","author":"Chen","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"157606","DOI":"10.1016\/j.phymed.2025.157606","article-title":"Therapeutic effects of modified Changfa Zirong Powder on androgenetic alopecia through the Wnt\/\u03b2-catenin signaling pathway","volume":"150","author":"Chen","year":"2026","journal-title":"Phytomedicine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13059-016-0881-8","article-title":"A survey of best practices for RNA-seq data analysis","volume":"17","author":"Conesa","year":"2016","journal-title":"Genome Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1159\/000211412","article-title":"Messenger RNA expression of steroidogenesis enzyme subtypes in the human pilosebaceous unit","volume":"9","author":"Courchay","year":"1996","journal-title":"Skin. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.3390\/ijms25052542","article-title":"The biology and genomics of human hair follicles: a focus on androgenetic alopecia","volume":"25","author":"Cuevas-Diaz Duran","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1007\/s40265-023-01880-x","article-title":"Androgenetic alopecia: therapy update","volume":"83","author":"Devjani","year":"2023","journal-title":"Drugs"},{"key":"B13","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/j.1469-7580.2008.01041.x","article-title":"A new scenario for the evolutionary origin of hair, feather, and avian scales","volume":"214","author":"Dhouailly","year":"2009","journal-title":"J. Anat."},{"key":"B14","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1046\/j.1523-1747.2001.01312.x","article-title":"Sebocytes are the key regulators of androgen homeostasis in human skin","volume":"116","author":"Fritsch","year":"2001","journal-title":"J. Invest. Dermatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"111247","DOI":"10.1016\/j.biopha.2021.111247","article-title":"Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia","volume":"137","author":"Fu","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1172\/JCI109835","article-title":"Pathogenesis of the henny feathering trait in the sebright bantam chicken. Increased conversion of androgen to estrogen in skin","volume":"66","author":"George","year":"1980","journal-title":"J. Clin. Invest."},{"key":"B17","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/71866","article-title":"The hair follicle as a gene therapy target","volume":"18","author":"Hoffman","year":"2000","journal-title":"Nat. Biotechnol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1177\/10815589251348920","article-title":"Free androgen index and its relation with female pattern hair loss","volume":"74","author":"Hosny","year":"2026","journal-title":"J. Investig. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.tcb.2011.09.005","article-title":"From 3D cell culture to organs-on-chips","volume":"21","author":"Huh","year":"2011","journal-title":"Trends Cell Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s41232-026-00417-5","article-title":"Age-related downregulation of dihydrotestosterone-inactivating enzymes in human scalp sebaceous glands","volume":"46","author":"Ikuno","year":"2026","journal-title":"Inflamm. Regen."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1096\/fj.02-0043fje","article-title":"Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth","volume":"16","author":"Inui","year":"2002","journal-title":"FASEB J."},{"key":"B22","doi-asserted-by":"publisher","first-page":"4086","DOI":"10.3390\/molecules27134086","article-title":"Connarus semidecandrus Jack Exerts anti-alopecia effects by targeting 5\u03b1-Reductase activity and an intrinsic apoptotic pathway","volume":"27","author":"Jang","year":"2022","journal-title":"Molecules"},{"key":"B23","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.bbrc.2020.06.098","article-title":"Ectodysplasin-A2 induces dickkopf 1 expression in human balding dermal papilla cells overexpressing the ectodysplasin A2 receptor","volume":"529","author":"Kwack","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1159\/000525067","article-title":"Dexamethasone, a synthetic glucocorticoid, induces the activity of androgen receptor in human dermal papilla cells","volume":"35","author":"Kwack","year":"2022","journal-title":"Skin. Pharmacol. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"21421","DOI":"10.1038\/s41598-023-48942-4","article-title":"Establishment and characterization of matched immortalized human frontal and occipital scalp dermal papilla cell lines from androgenetic alopecia","volume":"13","author":"Kwack","year":"2023","journal-title":"Sci. Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1111\/exd.12836","article-title":"Human hair follicle organ culture: theory, application and perspectives","volume":"24","author":"Langan","year":"2015","journal-title":"Exp. Dermatol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1097\/dss.0000000000004571","article-title":"Therapeutic applications of hair follicle transplantation beyond hair restoration: a comprehensive review","volume":"51","author":"Laufer-Britva","year":"2025","journal-title":"Dermatol Surg."},{"key":"B28","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-020-2352-3","article-title":"Hair-bearing human skin generated entirely from pluripotent stem cells","volume":"582","author":"Lee","year":"2020","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"939","DOI":"10.3390\/life14080939","article-title":"Genetic differences between Male and female pattern hair loss in a Korean population","volume":"14","author":"Lee","year":"2024","journal-title":"Life (Basel)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1111\/j.1365-2133.2012.10856.x","article-title":"Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt\/\u03b2-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia","volume":"166","author":"Leir\u00f3s","year":"2012","journal-title":"Br. J. Dermatol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"123963","DOI":"10.1016\/j.ijpharm.2024.123963","article-title":"Synergistic therapeutic effect of ginsenoside Rg3 modified minoxidil transfersomes (MXD-Rg3@TFs) on androgenic alopecia in C57BL\/6 mice","volume":"654","author":"Liu","year":"2024","journal-title":"Int. J. Pharm."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.1039\/d3mh00528c","article-title":"3D multicellular micropatterning biomaterials for hair regeneration and vascularization","volume":"10","author":"Ma","year":"2023","journal-title":"Mater Horiz."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1016\/j.jid.2025.03.042","article-title":"miR-574-3p and miR-125a-5p in adipose-derived mesenchymal stem cell exosomes synergistically target TGF-\u03b21\/SMAD2 signaling pathway for the treatment of androgenic alopecia","volume":"145","author":"Ma","year":"2025","journal-title":"J. Invest. Dermatol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41597-022-01846-w","article-title":"Comprehensive transcriptome data to identify downstream genes of testosterone signalling in dermal papilla cells","volume":"9","author":"Matsusaka","year":"2022","journal-title":"Sci. Data"},{"key":"B35","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1080\/17460441.2025.2473905","article-title":"Innovative strategies for the discovery of new drugs against androgenetic alopecia","volume":"20","author":"McElwee","year":"2025","journal-title":"Expert Opin. Drug Discov."},{"key":"B36","doi-asserted-by":"publisher","first-page":"947","DOI":"10.3390\/pharmaceutics14050947","article-title":"Minoxidil nanoparticles targeting hair follicles enhance hair growth in C57BL\/6 mice","volume":"14","author":"Oaku","year":"2022","journal-title":"Pharmaceutics"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.3390\/molecules30102246","article-title":"A natural inhibitor, 1'S-1'-Acetoxychavicol acetate, against testosterone-induced alopecia via NADPH oxidase regulation","volume":"30","author":"Park","year":"2025","journal-title":"Molecules"},{"key":"B38","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1056\/NEJM199908123410706","article-title":"The biology of hair follicles","volume":"341","author":"Paus","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1042\/0264-6021:3510067","article-title":"Human 3\u03b1-hydroxysteroid dehydrogenase isoforms (AKR1C1\u2013AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones","volume":"351","author":"Penning","year":"2000","journal-title":"Biochem. J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s00403-020-02178-8","article-title":"Towards developing an organotypic model for the preclinical study and manipulation of human hair matrix-dermal papilla interactions","volume":"314","author":"Platt","year":"2022","journal-title":"Arch. Dermatol Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1038\/s41598-023-28837-0","article-title":"Hypoxia inducible factor-1\u03b1 promotes trichogenic gene expression in human dermal papilla cells","volume":"13","author":"Seo","year":"2023","journal-title":"Sci. Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1186\/s12951-024-02689-w","article-title":"Exosomes derived from mouse vibrissa dermal papilla cells promote hair follicle regeneration during wound healing by activating Wnt\/\u03b2-catenin signaling pathway","volume":"22","author":"Shang","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1152\/physrev.2001.81.1.449","article-title":"Controls of hair follicle cycling","volume":"81","author":"Stenn","year":"2001","journal-title":"Physiol. Rev."},{"key":"B44","doi-asserted-by":"publisher","first-page":"7467","DOI":"10.3390\/ijms26157467","article-title":"Sulforaphane-rich broccoli sprout extract promotes hair regrowth in an androgenetic alopecia mouse model via enhanced dihydrotestosterone metabolism","volume":"26","author":"Subedi","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"17551","DOI":"10.1038\/s41598-025-02581-z","article-title":"Oxyresveratrol enhances hair regeneration in human dermal papilla cell and androgenetic alopecia mouse model","volume":"15","author":"Tran","year":"2025","journal-title":"Sci. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/s0531-5565(02)00093-1","article-title":"Molecular mechanisms of androgenetic alopecia","volume":"37","author":"Tr\u00fceb","year":"2002","journal-title":"Exp. Gerontol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"177264","DOI":"10.1016\/j.ejphar.2025.177264","article-title":"Natural phenylethanoid glycoside forsythoside A alleviates androgenetic alopecia by selectively inhibiting TRPV3 channels in mice","volume":"990","author":"Wang","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"146382","DOI":"10.1016\/j.ijbiomac.2025.146382","article-title":"Fucoidan treatment reverses hair loss and inhibits inflammatory responses in a mouse model of androgenetic alopecia","volume":"322","author":"Wang","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1210\/edrv-8-4-363","article-title":"The sebright bantam chicken and the genetic control of extraglandular aromatase","volume":"8","author":"Wilson","year":"1987","journal-title":"Endocr. Rev."},{"key":"B50","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.jconrel.2024.07.066","article-title":"Hybrid hair follicle stem cell extracellular vesicles co-delivering finasteride and gold nanoparticles for androgenetic alopecia treatment","volume":"373","author":"Wu","year":"2024","journal-title":"J. Control Release"},{"key":"B51","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1159\/000549505","article-title":"Preliminary study on platelet-rich plasma enhancing autophagy level and promoting hair growth in androgenetic alopecia model mice","volume":"53","author":"Xiao","year":"2025","journal-title":"Transfus. Med. Hemother"},{"key":"B52","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.actbio.2025.05.039","article-title":"Microenvironment-responsive recombinant collagen XVII-based composite microneedles for the treatment of androgenetic alopecia","volume":"200","author":"Xing","year":"2025","journal-title":"Acta Biomater."},{"key":"B53","doi-asserted-by":"publisher","first-page":"6174","DOI":"10.1021\/acs.nanolett.4c01843","article-title":"Polydopamine synergizes with Quercetin nanosystem to reshape the perifollicular microenvironment for accelerating hair regrowth in androgenetic alopecia","volume":"24","author":"Yang","year":"2024","journal-title":"Nano Lett."},{"key":"B54","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3390\/biomedicines14010160","article-title":"Integrated multi-omics analysis reveals dysregulated lipid metabolism as a novel mechanism in androgenetic alopecia","volume":"14","author":"Yang","year":"2026","journal-title":"Biomedicines"},{"key":"B55","doi-asserted-by":"publisher","first-page":"17532","DOI":"10.1021\/acsami.2c22814","article-title":"Dissolving microneedle patch integrated with microspheres for long-acting hair regrowth therapy","volume":"15","author":"Yin","year":"2023","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.3390\/ph14111128","article-title":"Alleviation of androgenetic alopecia with aqueous Paeonia lactiflora and Poria cocos extract intake through suppressing the steroid hormone and inflammatory pathway","volume":"14","author":"Zhang","year":"2021","journal-title":"Pharmaceuticals (Basel)"},{"key":"B57","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1021\/acs.jmedchem.3c01417","article-title":"Discovery of (2S) -N- (6-Cyano-5- (trifluoromethyl) pyridin-3-yl) -3- (6- (4-cyanophenyl) -3,6-diazabicyclo[3.1.1]heptan-3-yl)-2-hydroxy-2-methylpropanamide as a highly potent and selective topical androgen receptor antagonist for androgenetic alopecia treatment","volume":"67","author":"Zhang","year":"2024","journal-title":"J. Med. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/j.1600-0625.2008.00725.x","article-title":"Frontiers in sebaceous gland biology and pathology","volume":"17","author":"Zouboulis","year":"2008","journal-title":"Exp. Dermatol"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1935819\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:13:57Z","timestamp":1790673237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1935819\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":58,"alternative-id":["10.3389\/fphar.2026.1935819"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1935819","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"article-number":"1935819"}}