{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:41:09Z","timestamp":1768318869858,"version":"3.49.0"},"reference-count":74,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T00:00:00Z","timestamp":1703980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LAQV","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"LAQV","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"LAQV","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"LAQV","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"LAQV","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"LAQV","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"LAQV","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"LAQV","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"LAQV","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"LAQV","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"CIAFEL","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"CIAFEL","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"CIAFEL","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"CIAFEL","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"CIAFEL","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"CIAFEL","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"CIAFEL","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"CIAFEL","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"CIAFEL","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"CIAFEL","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"ITR","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"ITR","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"ITR","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"ITR","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"ITR","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"ITR","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"ITR","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"ITR","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"ITR","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"ITR","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"CITAB","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"CITAB","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"CITAB","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"CITAB","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"CITAB","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"CITAB","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"CITAB","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"CITAB","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"CITAB","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"CITAB","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"CECAV","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"CECAV","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"CECAV","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"CECAV","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"CECAV","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"CECAV","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"CECAV","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"CECAV","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"CECAV","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"CECAV","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"AL4animalS","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"AL4animalS","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"AL4animalS","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"AL4animalS","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"AL4animalS","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"AL4animalS","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"AL4animalS","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"AL4animalS","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"AL4animalS","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"AL4animalS","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"UnIC","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"UnIC","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"UnIC","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"UnIC","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"UnIC","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"UnIC","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"UnIC","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"UnIC","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"UnIC","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"UnIC","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"RISE Health Research Network: From the Lab to the Community","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["UIDB\/00617\/2020"],"award-info":[{"award-number":["UIDB\/00617\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["UIDB\/00772\/2020"],"award-info":[{"award-number":["UIDB\/00772\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["UIDB\/IC\/00051\/2020"],"award-info":[{"award-number":["UIDB\/IC\/00051\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDP\/00051\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)\/Ministry of Science, Technology and Higher Education (MCTES)","award":["LA\/P\/0053\/2020"],"award-info":[{"award-number":["LA\/P\/0053\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The salivary glands play a central role in the secretion of saliva, whose composition and volume affect oral and overall health. A lesser-explored dimension encompasses the possible changes in salivary gland proteomes in response to fluctuations in sex hormone levels. This study aimed to examine the effects of chronic exposure to testosterone on salivary gland remodeling, particularly focusing on proteomic adaptations. Therefore, male Wistar rats were implanted with subcutaneous testosterone-releasing devices at 14 weeks of age. Their submandibular glands were histologically and molecularly analyzed 47 weeks later. The results underscored a significant increase in gland mass after testosterone exposure, further supported by histologic evidence of granular duct enlargement. Despite increased circulating sex hormones, there was no detectable shift in the tissue levels of estrogen alpha and androgen receptors. GeLC-MS\/MS and subsequent bioinformatics identified 308 proteins in the submandibular glands, 12 of which were modulated by testosterone. Of note was the pronounced upregulation of Klk3 and the downregulation of Klk6 and Klk7 after testosterone exposure. Protein\u2013protein interaction analysis with the androgen receptor suggests that Klk3 is a potential target of androgenic signaling, paralleling previous findings in the prostate. This exploratory analysis sheds light on the response of salivary glands to testosterone exposure, providing proteome-level insights into the associated weight and histological changes.<\/jats:p>","DOI":"10.3390\/ijms25010550","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T06:37:12Z","timestamp":1704004632000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Long-Term Exposure to Supraphysiological Levels of Testosterone Impacts Rat Submandibular Gland Proteome"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1218-5749","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Valente-Santos","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-5805","authenticated-orcid":false,"given":"Rui","family":"Vitorino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-6149","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Sousa-Mendes","sequence":"additional","affiliation":[{"name":"UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4044","authenticated-orcid":false,"given":"Paula","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4879-8624","authenticated-orcid":false,"given":"Bruno","family":"Cola\u00e7o","sequence":"additional","affiliation":[{"name":"Veterinary and Animal Research Centre (CECAV), Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Department of Animal Science, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5572-6317","authenticated-orcid":false,"given":"Ana I.","family":"Faustino-Rocha","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Comprehensive Health Research Center, Department of Zootechnics, School of Sciences and Technology, University of \u00c9vora, 7006-554 \u00c9vora, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Neuparth","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto, 4200-450 Porto, Portugal"},{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-3596","authenticated-orcid":false,"given":"Adelino","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-5917","authenticated-orcid":false,"given":"Jos\u00e9 Alberto","family":"Duarte","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto, 4200-450 Porto, Portugal"},{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-4051","authenticated-orcid":false,"given":"Rita","family":"Ferreira","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Francisco","family":"Amado","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Toan, N.K., and Ahn, S.G. (2021). Aging-Related Metabolic Dysfunction in the Salivary Gland: A Review of the Literature. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115835"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0074-7696(08)60101-1","article-title":"Action of Testosterone on the Differentiation and Secretory Activity of a Target Organ: The Submaxillary Gland of the Mouse","volume":"50","year":"1977","journal-title":"Int. Rev. Cytol."},{"key":"ref_3","first-page":"3","article-title":"Androgen Receptor Structure, Function and Biology: From Bench to Bedside","volume":"37","author":"Davey","year":"2016","journal-title":"Clin. Biochem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1056\/NEJM197606102942405","article-title":"Mechanism of Action of the Sex Steroid Hormones (First of Three Parts)","volume":"294","author":"Chan","year":"1976","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1177\/154405910508401218","article-title":"Influence of Androgens on Gene Expression in the BALB\/c Mouse Submandibular Gland","volume":"84","author":"Treister","year":"2005","journal-title":"J. Dent. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0003-9969(93)90136-A","article-title":"Immunohistochemical Demonstration of Androgen Receptors in Human Salivary Glands","volume":"38","author":"Laine","year":"1993","journal-title":"Arch. Oral Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/0003-9969(85)90082-2","article-title":"Effects of Testosterone and Its Metabolites in Relation to Androgen-Binding Activity in Murine Submandibular Salivary Glands","volume":"30","author":"Minetti","year":"1985","journal-title":"Arch. Oral Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/edrv-8-1-1","article-title":"Biological Actions of Androgens","volume":"8","author":"Mooradian","year":"1987","journal-title":"Endocr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1267\/ahc.12013","article-title":"Anatomy and Histology of Rodent and Human Major Salivary Glands\u2014Overview of the Japan Salivary Gland Society-Sponsored Workshop","volume":"45","author":"Amano","year":"2012","journal-title":"Acta Histochem. Cytochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/odi.12840","article-title":"Comparing Human and Mouse Salivary Glands: A Practice Guide for Salivary Researchers","volume":"25","author":"Maruyama","year":"2019","journal-title":"Oral Diseases"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dalin, M.G., Watson, P.A., Ho, A.L., and Morris, L.G.T. (2017). Androgen Receptor Signaling in Salivary Gland Cancer. Cancers, 9.","DOI":"10.3390\/cancers9020017"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"a030452","DOI":"10.1101\/cshperspect.a030452","article-title":"Androgen Signaling in Prostate Cancer","volume":"7","author":"Dai","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1001\/jamainternmed.2013.6895","article-title":"Trends in androgen prescribing in the United States, 2001 to 2011","volume":"173","author":"Baillargeon","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1530\/JOE-12-0455","article-title":"Testosterone: A metabolic hormone in health and disease","volume":"217","author":"Kelly","year":"2013","journal-title":"J. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1111\/andr.12774","article-title":"Testosterone replacement therapy","volume":"8","author":"Barbonetti","year":"2020","journal-title":"Andrology"},{"key":"ref_16","first-page":"35","article-title":"A review of testosterone supplementation and cardiovascular risk","volume":"61","author":"Jhawar","year":"2023","journal-title":"Rom. J. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11934-018-0812-1","article-title":"The Role of Testosterone Therapy in the Setting of Prostate Cancer","volume":"19","author":"Rodriguez","year":"2018","journal-title":"Curr. Urol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.2164\/jandrol.112.017160","article-title":"Aging and Declining Testosterone: Past, Present, and Hopes for the Future","volume":"33","author":"Zirkin","year":"2012","journal-title":"J. Androl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/bs.vh.2020.12.014","article-title":"Aging and Sex Hormones in Males","volume":"115","author":"Decaroli","year":"2021","journal-title":"Vitam. Horm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1177\/00220345211004842","article-title":"Disease-Induced Changes in Salivary Gland Function and the Composition of Saliva","volume":"100","author":"Proctor","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref_21","unstructured":"Ekstr\u00f6m, J., Khosravani, N., Castagnola, M., and Messana, I. (2012). Dysphagia, Springer."},{"key":"ref_22","first-page":"841","article-title":"Hyposalivation in Elderly Patients","volume":"72","author":"Gupta","year":"2006","journal-title":"J. Can. Dent. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/ncpendmet1050","article-title":"Testosterone and Ill-Health in Aging Men","volume":"5","author":"Yeap","year":"2009","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1532-5415.1989.tb02644.x","article-title":"Salivary Gland Fluid Secretion During Aging","volume":"37","author":"Baum","year":"1989","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/jemt.1070280308","article-title":"Structural and Functional Changes in Salivary Glands During Aging","volume":"28","author":"Kim","year":"1994","journal-title":"Microsc. Res. Tech."},{"key":"ref_26","first-page":"624","article-title":"The Laboratory Rat: Relating Its Age with Human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1067\/mpr.2001.113778","article-title":"A Review of Saliva: Normal Composition, Flow, and Function","volume":"85","author":"Humphrey","year":"2001","journal-title":"J. Prosthet. Dent."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2165\/00007256-199826010-00002","article-title":"Saliva Composition and Exercise","volume":"26","author":"Chicharro","year":"1998","journal-title":"Sports Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/1557988314539000","article-title":"High Estrogen in Men After Injectable Testosterone Therapy: The Low T Experience","volume":"9","author":"Tan","year":"2015","journal-title":"Am. J. Mens. Health"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Han, X., Xia, X., Zhuo, Y., Hua, L., Yu, G., Bu, G., Cao, X., Du, X., Liang, Q., and Zeng, X. (2022). RNA-seq coupling two different methods of castration reveals new insights into androgen deficiency-caused degeneration of submaxillary gland in male Sprague Dawley rats. BMC Genom., 23.","DOI":"10.1186\/s12864-022-08521-9"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Koistinen, H., K\u00fcnnapuu, J., and Jeltsch, M. (2021). Klk3 in the Regulation of Angiogenesis\u2014Tumorigenic or Not?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413545"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nauroy, P., and Nystr\u00f6m, A. (2019). Kallikreins: Essential Epidermal Messengers for Regulation of the Skin Microenvironment During Homeostasis, Repair and Disease. Matrix Biol. Plus, 6.","DOI":"10.1016\/j.mbplus.2019.100019"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"777619","DOI":"10.3389\/fmed.2021.777619","article-title":"Human Tissue Kallikreins-Related Peptidases Are Targets for the Treatment of Skin Desquamation Diseases","volume":"8","author":"Zani","year":"2022","journal-title":"Front. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"946572","DOI":"10.1155\/2015\/946572","article-title":"Involvement of Kallikrein-Related Peptidases in Normal and Pathologic Processes","volume":"2015","author":"Stefanini","year":"2015","journal-title":"Dis. Markers"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41569-019-0211-4","article-title":"Testosterone Replacement Therapy and Cardiovascular Risk","volume":"16","author":"Basaria","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_36","first-page":"427","article-title":"The Benefits and Risks of Testosterone Replacement Therapy: A Review","volume":"5","author":"Bassil","year":"2009","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.eururo.2015.12.005","article-title":"Testosterone Therapy in Men with Prostate Cancer","volume":"69","author":"Kaplan","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ecl.2021.11.005","article-title":"Testosterone Replacement Therapy in Hypogonadal Men","volume":"51","author":"Wang","year":"2022","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_39","unstructured":"Suttie, A.W. (2018). Boorman\u2019s Pathology of the Rat: Reference and Atlas, Academic Press. [2nd ed.]."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kunath, A., Weiner, J., Krause, K., Rehders, M., Pejkovska, A., Gericke, M., Biniossek, M.L., Dommel, S., Kern, M., and Ribas-Latre, A. (2021). Role of Kallikrein 7 in Body Weight and Fat Mass Regulation. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020131"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00018-017-2658-y","article-title":"Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high fat diet-induced obesity by counteracting adipose tissue inflammation in vivo","volume":"75","author":"Zieger","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.2174\/0929867328666210915104537","article-title":"The Role of Kallikrein 7 in Tumorigenesis","volume":"29","author":"Xiang","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"356","DOI":"10.5230\/jgc.2018.18.e35","article-title":"KLK6 Promotes Growth, Migration, and Invasion of Gastric Cancer Cells","volume":"18","author":"Zhu","year":"2018","journal-title":"J. Gastric Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"824","DOI":"10.3892\/ol.2021.13085","article-title":"KLK6 mediates stemness and metabolism of gastric carcinoma cells via the PI3K\/AKT\/mTOR signaling pathway","volume":"22","author":"Zhou","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1369\/jhc.5A6803.2005","article-title":"Human Kallikrein 6 Expression in Salivary Gland Tumors","volume":"54","author":"Darling","year":"2006","journal-title":"J. Histochem. Cytochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/nrc1474","article-title":"The Emerging Roles of Human Tissue Kallikreins in Cancer","volume":"4","author":"Diamandis","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_47","first-page":"22","article-title":"Tissue Kallikrein Proteolytic Cascade Pathways in Normal Physiology and Cancer","volume":"1776","author":"Pampalakis","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1515\/hsz-2014-0129","article-title":"Putative Kallikrein Substrates and Their (Patho)Biological Functions","volume":"395","author":"Yu","year":"2014","journal-title":"Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.canlet.2006.12.018","article-title":"Human Tissue Kallikreins: The Cancer Biomarker Family","volume":"249","author":"Paliouras","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1177\/41.1.8417114","article-title":"Secretion of Glandular Kallikrein and Renin from the Basolateral Pole of Mouse Submandibular Duct Cells: An Immunocytochemical Study","volume":"41","author":"Penschow","year":"1993","journal-title":"J. Histochem. Cytochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1160\/TH13-04-0275","article-title":"Prostate-Specific Kallikrein-Related Peptidases and Their Relation to Prostate Cancer Biology and Detection; Established Relevance and Emerging Roles","volume":"110","author":"Thorek","year":"2013","journal-title":"Thromb. Haemost."},{"key":"ref_52","first-page":"201","article-title":"Human Kallikrein 3 (Prostate Specific Antigen) and Human Kallikrein 5 Expression in Salivary Gland Tumors","volume":"21","author":"Darling","year":"2006","journal-title":"Int. J. Biol. Markers"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/ijc.20605","article-title":"Expression of Prostate-Specific Antigen (PSA) and Human Glandular Kallikrein 2 (hK2) in Ileum and Other Extraprostatic Tissues","volume":"113","author":"Olsson","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4103\/1008-682X.140966","article-title":"Testosterone and benign prostatic hyperplasia","volume":"17","author":"Jarvis","year":"2015","journal-title":"Asian J. Androl."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/0970-1591.124197","article-title":"Risks of testosterone replacement therapy in men","volume":"30","author":"Osterberg","year":"2014","journal-title":"Indian J. Urol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1210\/er.2009-0034","article-title":"Kallikreins on Steroids: Structure, Function, and Hormonal Regulation of Prostate-Specific Antigen and the Extended Kallikrein Locus","volume":"31","author":"Lawrence","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s40618-014-0051-3","article-title":"Benign prostatic hyperplasia: A new metabolic disease?","volume":"37","author":"Vignozzi","year":"2014","journal-title":"J. Endocrinol. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ajur.2019.10.003","article-title":"The role of the androgen receptor in prostate development and benign prostatic hyperplasia: A review","volume":"7","author":"Vickman","year":"2020","journal-title":"Asian J. Urol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"bqaa215","DOI":"10.1210\/endocr\/bqaa215","article-title":"The Role of Androgen Signaling in Male Sexual Development at Puberty","volume":"162","author":"Rey","year":"2021","journal-title":"Endocrinology"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Messner, E.A., Steele, T.M., Tsamouri, M.M., Hejazi, N., Gao, A.C., Mudryj, M., and Ghosh, P.M. (2020). The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100422"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1152\/physrev.00018.2016","article-title":"Estrogens in Male Physiology","volume":"97","author":"Cooke","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Belluti, S., Imbriano, C., and Casarini, L. (2023). Nuclear Estrogen Receptors in Prostate Cancer: From Genes to Function. Cancers, 15.","DOI":"10.3390\/cancers15184653"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"839005","DOI":"10.3389\/fendo.2022.839005","article-title":"Role of estrogen receptors in health and disease","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0303-7207(00)00279-3","article-title":"Interactions between androgen and estrogen receptors and the effects on their transactivational properties","volume":"167","author":"Gottlieb","year":"2000","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrc4016","article-title":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","volume":"15","author":"Watson","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"288","DOI":"10.5534\/wjmh.180040","article-title":"Role of Androgen Receptor in Prostate Cancer: A Review","volume":"37","author":"Fujita","year":"2019","journal-title":"World J. Men\u2019s Health"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6570","DOI":"10.1158\/1078-0432.CCR-14-1746","article-title":"Alterations Associated with Androgen Receptor Gene Activation in Salivary Duct Carcinoma of Both Sexes: Potential Therapeutic Ramifications","volume":"20","author":"Mitani","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/ng0495-401","article-title":"In Vivo Amplification of the Androgen Receptor Gene and Potential Role in Progression of Human Prostate Cancer","volume":"9","author":"Visakorpi","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/pros.20282","article-title":"Possible Role of Adaptive Mutation in Resistance to Antiandrogen in Prostate Cancer Cells","volume":"65","author":"Hara","year":"2005","journal-title":"Prostate"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"16759","DOI":"10.1073\/pnas.1012443107","article-title":"Constitutively Active Androgen Receptor Splice Variants Expressed in Castration-Resistant Prostate Cancer Require Full-Length Androgen Receptor","volume":"107","author":"Watson","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.urolonc.2008.06.002","article-title":"Oncogenic Activation of Androgen Receptor","volume":"27","author":"Kung","year":"2009","journal-title":"Urol. Oncol."},{"key":"ref_72","first-page":"627","article-title":"Effects of testosterone and exercise training on bone microstructure of rats","volume":"15","author":"Fardilha","year":"2022","journal-title":"Vet. World"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of Structural Proteins During the Assembly of the Head of Bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/prca.200800183","article-title":"Towards Defining the Whole Salivary Peptidome","volume":"3","author":"Vitorino","year":"2009","journal-title":"Proteom. Clin. Appl."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/550\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:45:11Z","timestamp":1760132711000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,31]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25010550"],"URL":"https:\/\/doi.org\/10.3390\/ijms25010550","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,31]]}}}