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In peripheral tissues, androgen exposure is regulated mainly by local steroid metabolism, which can activate or inactivate androgens independently of systemic concentrations. In the scalp, 5\u03b1-reductase\u2013mediated generation of dihydrotestosterone (DHT) has been studied extensively in relation to conditions such as androgenetic alopecia. In contrast, age-related regulation of DHT-inactivating pathways, including the aldo\u2013keto reductase family 1 member C (AKR1C) family, remains insufficiently defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined AKR1C1\u20134 expression in scalp tissues from individuals of different ages, sexes, and hair loss conditions using immunohistochemistry (IHC), quantitative PCR (qPCR), and reanalysis of publicly available RNA-sequencing (RNA-seq) datasets. Androgen receptor (AR) localization was assessed in multiple scalp compartments.\n                      <jats:italic>AKR1C<\/jats:italic>\n                      expression was also analyzed in immortalized human sebaceous gland cells (SEB-1) and dermal papilla cells (DPCs). In addition, the effect of sulforaphane on AKR1C expression was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>AKR1Cs<\/jats:italic>\n                      were strongly expressed in male sebaceous glands (SGs) but declined with age. AKR1C4, previously considered liver specific, was detected in SGs and hair follicles (HFs) by IHC and further confirmed by qPCR in SEB-1 cells and DPCs. AR expression was predominant in SGs, with lower levels in sweat glands, the epidermal granular layer, and the HF infundibulum, but not detected in dermal papillae and bulge regions. AR localization was cytoplasmic in the epidermis but nuclear in SGs and sweat glands, and was unaffected by age, sex, or hair loss condition. Sulforaphane treatment upregulated\n                      <jats:italic>AKR1C<\/jats:italic>\n                      expression in both SEB-1 cells and DPCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identify scalp SGs as a principal site of AR expression and AKR1C-mediated androgen inactivation, including AKR1C4, and demonstrate that AKR1C expression in SGs is sex dependent and declines with age. These findings suggest that age-associated changes in SG steroid metabolism may influence local androgen metabolism within the scalp microenvironment, with implications for HF homeostasis during aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41232-026-00417-5","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T02:56:46Z","timestamp":1775530606000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Age-related downregulation of dihydrotestosterone-inactivating enzymes in human scalp sebaceous glands"],"prefix":"10.1186","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1498-3802","authenticated-orcid":false,"given":"Yasuaki","family":"Ikuno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukie","family":"Kande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Arakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriki","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3764-6238","authenticated-orcid":false,"given":"Hayato","family":"Naka-Kaneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"417_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.mce.2017.08.016","volume":"465","author":"L Schiffer","year":"2018","unstructured":"Schiffer L, Arlt W, Storbeck KH. 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Nature. 2021;592(7854):428\u201332. https:\/\/doi.org\/10.1038\/s41586-021-03417-2.","journal-title":"Nature"}],"container-title":["Inflammation and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41232-026-00417-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41232-026-00417-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41232-026-00417-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:17:04Z","timestamp":1777432624000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41232-026-00417-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["417"],"URL":"https:\/\/doi.org\/10.1186\/s41232-026-00417-5","relation":{},"ISSN":["1880-8190"],"issn-type":[{"value":"1880-8190","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"9 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The use of human scalp tissue specimens was approved by the Ethics Committee of Shiga University of Medical Science (Project title: Age-related changes in pro- and anti-inflammatory factors in human skin), Approval No. R2024-036, Date of approval: 25 July 2024). The requirement for individual informed consent was waived, and an opt-out approach approved by the ethics committee was applied in accordance with institutional and national guidelines.The immortalized human sebaceous gland cell line (SEB-1) was kindly provided by the Penn State Research Foundation. The original establishment of this cell line was conducted under appropriate institutional ethical approval, as described in the original publication [\n                      \n                      ].Human dermal papilla cells (DPCs) were purchased from PromoCell (Cat. no. c-12071). According to the supplier\u2019s documentation, these cells were obtained from human donors with written informed consent and local ethics committee approval.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The requirement for individual consent for publication was waived, and an opt-out approach approved by the ethics committee was applied in accordance with institutional and national guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20"}}