{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:12:33Z","timestamp":1790957553310,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"DFG","doi-asserted-by":"publisher","award":["427588170"],"award-info":[{"award-number":["427588170"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Clonidine has been used in clinical medicine, e.g., to treat high blood pressure and other conditions. Animal studies have linked its use to impairments of male reproductive functions, and although only a few reports exist for the human species, such actions may exist in man as well. The underlying reasons and, specifically, possible actions of clonidine at the level of the testis are not known. Introduction: Clonidine is an agonist at the \u03b12A-adrenoceptor (ADRA2A), which, as data bank mining indicated, is expressed by several cells of the human testis. The human testis and most of its cells are, however, not readily accessible to experimental testing. Cells from the peritubular wall compartment (human testicular peritubular cells; HTPCs) are the exception. Methods and Results: As shown by immunohistochemical\/immunocytochemical and PCR techniques these cells express ADRA2A and retain expression upon isolation and culture. When tested over a concentration range (1\u20131000 \u00b5M) and 24 h, clonidine did not visibly affect HTPC morphology but significantly stimulated IL6 mRNA levels in a concentration-dependent manner. ELISA measurements of cell culture supernatants confirmed a stimulatory action of clonidine (10 \u00b5M) on secreted IL6. When examined in collagen gel contraction assays of HTPCs, clonidine (10 \u00b5M) exerted a slight relaxing action, while a proteomic study revealed that clonidine (10 \u00b5M) did not significantly change cellular protein abundance of HTPCs after 24 h (data available via ProteomeXchange with identifier PXD052220). Conclusion: Thus, ADRA2A-bearing cells in the human testis are targets for catecholamines and drugs such as clonidine. The results of this HTPCs-focused study only show the tip of the iceberg. It is likely that catecholamines\/catecholaminergic drugs have the potential to interfere with human testicular functions.<\/jats:p>","DOI":"10.3390\/jcm13154357","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T14:31:07Z","timestamp":1721917867000},"page":"4357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Catecholamine and Drug Target \u03b12A-Adrenoceptor in Human Testis and Human Testicular Peritubular Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Welter","family":"Harald","sequence":"first","affiliation":[{"name":"Biomedical Center, Cell Biology, Anatomy III, Faculty of Medicine, Ludwig Maximilian University of Munich, 82152 Planegg-Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kreitmair","family":"Nicole","sequence":"additional","affiliation":[{"name":"Biomedical Center, Cell Biology, Anatomy III, Faculty of Medicine, Ludwig Maximilian University of Munich, 82152 Planegg-Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schneider","family":"Michaela","sequence":"additional","affiliation":[{"name":"Biomedical Center, Cell Biology, Anatomy III, Faculty of Medicine, Ludwig Maximilian University of Munich, 82152 Planegg-Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herrmann","family":"Carola","sequence":"additional","affiliation":[{"name":"Biomedical Center, Cell Biology, Anatomy III, Faculty of Medicine, Ludwig Maximilian University of Munich, 82152 Planegg-Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schmid","family":"Nina","sequence":"additional","affiliation":[{"name":"Biomedical Center, Cell Biology, Anatomy III, Faculty of Medicine, Ludwig Maximilian University of Munich, 82152 Planegg-Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5534-8539","authenticated-orcid":false,"given":"Stepanov","family":"Youli","sequence":"additional","affiliation":[{"name":"Gene Center Munich, Laboratory for Functional Genome Analysis (LAFUGA), Ludwig Maximilian University of Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-3211","authenticated-orcid":false,"given":"Fr\u00f6hlich","family":"Thomas","sequence":"additional","affiliation":[{"name":"Gene Center Munich, Laboratory for Functional Genome Analysis (LAFUGA), Ludwig Maximilian University of Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00f6hn","family":"Frank-Michael","sequence":"additional","affiliation":[{"name":"Andrologicum, 80331 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pickl","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Urologie und Andrologie am Promenadenplatz, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trottmann","family":"Matthias","sequence":"additional","affiliation":[{"name":"Urologie und Andrologie am Promenadenplatz, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9388-4639","authenticated-orcid":false,"given":"Mayerhofer","family":"Artur","sequence":"additional","affiliation":[{"name":"Biomedical Center, Cell Biology, Anatomy III, Faculty of Medicine, Ludwig Maximilian University of Munich, 82152 Planegg-Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","first-page":"2075","article-title":"Effects of antihypertensive agents on sexual function","volume":"44","author":"Weiss","year":"1991","journal-title":"Am. Fam. Physician"},{"key":"ref_2","first-page":"236","article-title":"Antihypertensive therapy and male sexual dysfunction","volume":"234","author":"Hogan","year":"1980","journal-title":"Psychosomatics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1136\/bmj.3.5720.440","article-title":"Treatment of hypertension with clonidine","volume":"3","author":"MacDougall","year":"1970","journal-title":"Br. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S0140-6736(19)33004-1","article-title":"Attention-deficit hyperactivity disorder","volume":"395","author":"Posner","year":"2020","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/pro.5560020802","article-title":"Structure, function, and regulation of adrenergic receptors","volume":"2","author":"Strosberg","year":"1993","journal-title":"Protein Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3949\/ccjm.57.5.481","article-title":"Adrenergic receptors: Structure and function","volume":"57","author":"Graham","year":"1990","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0014-2999(71)90203-2","article-title":"The peripheral circulatory effects of clonidine and their role in the production of arterial hypotension","volume":"14","author":"Shaw","year":"1971","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1124\/pr.118.016311","article-title":"Imidazoline Receptor System: The Past, the Present, and the Future","volume":"72","author":"Bousquet","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_9","first-page":"267","article-title":"Male Infertility during Antihypertensive Therapy: Are We Addressing Correctly The Problem?","volume":"10","author":"Vitale","year":"2016","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00345-006-0136-5","article-title":"Adverse effects of drug therapies on male and female sexual function","volume":"24","author":"Stadler","year":"2006","journal-title":"World J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3233\/JRS-170743","article-title":"Impaired reproduction after exposure to ADHD drugs: Systematic review of animal studies","volume":"29","author":"Danborg","year":"2017","journal-title":"Int. J. Risk Saf. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejphar.2006.05.045","article-title":"Sympathetic neurotransmission in the rat testicular capsule: Functional characterization and identification of mRNA encoding alpha1-adrenoceptor subtypes","volume":"543","author":"Jurkiewicz","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejphar.2014.01.027","article-title":"Effects of clonidine in the isolated rat testicular capsule","volume":"726","author":"Rodrigues","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"D1438","DOI":"10.1093\/nar\/gkad944","article-title":"The IUPHAR\/BPS Guide to PHARMACOLOGY in 2024","volume":"52","author":"Harding","year":"2024","journal-title":"Nucl. Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1210\/jc.2005-2169","article-title":"Isolation and cultivation of human testicular peritubular cells: A new model for the investigation of fibrotic processes in the human testis and male infertility","volume":"91","author":"Albrecht","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R107","DOI":"10.1530\/REP-12-0497","article-title":"Human testicular peritubular cells: More than meets the eye","volume":"145","author":"Mayerhofer","year":"2013","journal-title":"Reproduction"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liebich, A., Schmid, N., Koupourtidou, C., Herrmann, C., Dietrich, K.G., Welter, H., Ninkovic, J., and Mayerhofer, A. (2022). The Molecular Signature of Human Testicular Peritubular Cells Revealed by Single-Cell Analysis. Cells, 11.","DOI":"10.3390\/cells11223685"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2018.01.027","article-title":"Alpha 1 adrenergic receptor-mediated inflammatory responses in human testicular peritubular cells","volume":"474","author":"Rossi","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Eubler, K., Rantakari, P., Gerke, H., Herrmann, C., Missel, A., Schmid, N., Walenta, L., Lahiri, S., Imhof, A., and Strauss, L. (2021). Exploring the Ion Channel TRPV2 and Testicular Macrophages in Mouse Testis. Int J Mol Sci., 22.","DOI":"10.3390\/ijms22094727"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12964-021-00755-6","article-title":"Role of \u03b1- and \u03b2-adrenergic signaling in phenotypic targeting: Significance in benign and malignant urologic disease","volume":"19","author":"Archer","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Frungieri, M.B., and Mayerhofer, A. (2024). Biogenic amines in the testis: Sources, receptors and actions. Front. Endocrinol., 20.","DOI":"10.3389\/fendo.2024.1392917"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Welter, H., Herrmann, C., Dellweg, N., Missel, A., Thanisch, C., Urbanski, H.F., K\u00f6hn, F.M., Schwarzer, J.U., M\u00fcller-Taubenberger, A., and Mayerhofer, A. (2020). The Glucocorticoid Receptor NR3C1 in Testicular Peritubular Cells is Developmentally Regulated and Linked to the Smooth Muscle-Like Cellular Phenotype. J. Clin. Med., 9.","DOI":"10.3390\/jcm9040961"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1210\/en.2007-1064","article-title":"Exploring human testicular peritubular cells: Identification of secretory products and regulation by tumor necrosis factor-alpha","volume":"149","author":"Schell","year":"2008","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1111\/andr.283","article-title":"Epididymal contraction and sperm parameters are affected by clonidine","volume":"2","author":"Vilela","year":"2014","journal-title":"Andrology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.mce.2014.06.011","article-title":"Angiotensin II regulates testicular peritubular cell function via AT1 receptor: A specific situation in male infertility","volume":"393","author":"Welter","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Stepanov, Y.K., Speidel, J.D., Herrmann, C., Schmid, N., Behr, R., K\u00f6hn, F.M., St\u00f6ckl, J.B., Pickl, U., Trottmann, M., and Fr\u00f6hlich, T. (2022). Profound Effects of Dexamethasone on the Immunological State, Synthesis and Secretion Capacity of Human Testicular Peritubular Cells. Cells, 11.","DOI":"10.3390\/cells11193164"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Stepanov, Y.K., Herrmann, C., St\u00f6ckl, J.B., K\u00f6hn, F.M., Pickl, U., Trottmann, M., Fr\u00f6hlich, T., Mayerhofer, A., and Welter, H. (2024). Prolonged exposure to dexamethasone alters the proteome and cellular phenotype of human testicular peritubular cells. Proteomics, e2300616.","DOI":"10.1002\/pmic.202300616"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-4939-7493-1_7","article-title":"Perseus: A Bioinformatics Platform for Integrative Analysis of Proteomics Data in Cancer Research","volume":"1711","author":"Tyanova","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Bai","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1681\/ASN.2019040335","article-title":"Single-Cell Transcriptomic Map of the Human and Mouse Bladders","volume":"30","author":"Yu","year":"2019","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e62885","DOI":"10.7554\/eLife.62885","article-title":"ATP activation of peritubular cells drives testicular sperm transport","volume":"10","author":"Fleck","year":"2021","journal-title":"Elife"},{"key":"ref_34","first-page":"681","article-title":"Mechanism of relaxant effect of clonidine in isolated bovine tracheal smooth muscle","volume":"286","author":"Arimitsu","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1007\/s00424-021-02609-z","article-title":"Mechanisms underlying spontaneous phasic contractions and sympathetic control of smooth muscle in the rat caudal epididymis","volume":"473","author":"Mitsui","year":"2021","journal-title":"Pflugers Arch."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1093\/humrep\/deq170","article-title":"Glial cell line-derived neurotrophic factor is constitutively produced by human testicular peritubular cells and may contribute to the spermatogonial stem cell niche in man","volume":"25","author":"Spinnler","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.mce.2018.01.022","article-title":"Prostaglandin E2 (PGE2) is a testicular peritubular cell-derived factor involved in human testicular homeostasis","volume":"473","author":"Rossi","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"E1227","DOI":"10.1210\/jc.2013-4199","article-title":"Human testicular peritubular cells host putative stem Leydig cells with steroidogenic capacity","volume":"99","author":"Landreh","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1111\/andr.12509","article-title":"Insights into the role of androgen receptor in human testicular peritubular cells","volume":"6","author":"Mayer","year":"2018","journal-title":"Andrology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11456","DOI":"10.1038\/s41598-021-90872-6","article-title":"Interleukin-6 deficiency modulates testicular function by increasing the expression of suppressor of cytokine signaling 3 (SOCS3) in mice","volume":"11","author":"Freitas","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.4049\/jimmunol.167.8.4527","article-title":"Immunoendocrine interactions during chronic cysticercosis determine male mouse feminization: Role of IL-6","volume":"167","author":"Baig","year":"2001","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2131\/jts.17.41","article-title":"Disturbance or relatively important actions of antihypertensives, antifungal agent and opiate antagonist to the testicular steroidogenesis in rat","volume":"17","author":"Masubuchi","year":"1992","journal-title":"J. Toxicol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.mce.2017.11.016","article-title":"Interleukin 6 inhibits the differentiation of rat stem Leydig cells","volume":"472","author":"Wang","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1089\/107999099312948","article-title":"Dose-dependent effects of recombinant human interleukin-6 on the pituitary-testicular axis","volume":"19","author":"Tsigos","year":"1999","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/cvr\/cvq014","article-title":"Sympathetic alpha(2)-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload","volume":"86","author":"Gilsbach","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13233","DOI":"10.1074\/jbc.M807535200","article-title":"Epitope-tagged receptor knock-in mice reveal that differential desensitization of alpha2-adrenergic responses is because of ligand-selective internalization","volume":"284","author":"Lu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e242859","DOI":"10.1001\/jamanetworkopen.2024.2859","article-title":"Attention-Deficit\/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes","volume":"7","author":"Taipale","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_48","first-page":"4232","article-title":"Efficacy of clonidine in the treatment of children with tic disorder co-morbid with attention deficit hyperactivity disorder","volume":"27","author":"Zeng","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.fertnstert.2021.03.033","article-title":"Influence of paternal age on assisted reproductive technology cycles and perinatal outcomes","volume":"116","author":"Marsidi","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chan, P.T.K., and Robaire, B. (2022). Advanced Paternal Age and Future Generations. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.897101"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"109380","DOI":"10.1016\/j.drugalcdep.2022.109380","article-title":"Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis","volume":"233","author":"Friedman","year":"2022","journal-title":"Drug Alcohol. Depend."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMp2303120","article-title":"Xylazine\u2014Medical and Public Health Imperatives","volume":"388","author":"Gupta","year":"2023","journal-title":"N. Engl. J. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/15\/4357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:23:33Z","timestamp":1760109813000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/15\/4357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,25]]},"references-count":52,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["jcm13154357"],"URL":"https:\/\/doi.org\/10.3390\/jcm13154357","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,25]]}}}