{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:06:27Z","timestamp":1790417187889,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Extracellular purines, in particular ATP and adenosine, are regulators of physiological and pathophysiological processes throughout the human body. Roles in the human testis are emerging and include actions on peritubular cells, which form the wall of seminiferous tubules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Here, we examined adenosine\u2010evoked consequences in human testicular peritubular cells (HTPCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      HTPCs were isolated from testicular samples, cultured and examined. The ability of HTPCs to generate extracellular adenosine was investigated. Acute actions of adenosine were evaluated by monitoring intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      levels and signaling pathways. Studies with selective adenosine receptor agonists and knockdown of the\n                      <jats:italic>ADORA2B<\/jats:italic>\n                      receptor were performed. Transcriptional and translational changes evoked by adenosine were evaluated using scRNA\u2010seq and proteomic studies. Regulation of\n                      <jats:italic>ADORA2B<\/jats:italic>\n                      by the synthetic glucocorticoid dexamethasone and 5\u237a\u2010dihydrotestosterone were analyzed by qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HTPCs metabolized extracellular ATP and generated adenosine. They express the required enzymatic machinery and functional adenosine receptors (\n                      <jats:italic>ADORA1<\/jats:italic>\n                      ,\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      , and\n                      <jats:italic>ADORA2B<\/jats:italic>\n                      ), which likely mediated adenosine action on MAPK pathways and intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transients. Proteomic studies revealed that exposure to adenosine for 24 h affected the abundance of 38 proteins. Among others, IL33 and StAR were strongly increased. Agonist\u2010 and siRNA\u2010mediated knockdown studies identified\n                      <jats:italic>ADORA2B<\/jats:italic>\n                      as a key mediator of\n                      <jats:italic>IL33<\/jats:italic>\n                      upregulation.\n                      <jats:italic>StAR<\/jats:italic>\n                      upregulation was accompanied by increased pregnenolone formation. The proteomic changes were confirmed by scRNA\u2010seq, which revealed additional transcriptional remodeling, including\n                      <jats:italic>HIF1A<\/jats:italic>\n                      induction and enrichment of pathways linked to cell communication, migration and inflammation. Dexamethasone reduced\n                      <jats:italic>ADORA2B<\/jats:italic>\n                      levels, implying plasticity of this member of the purinergic signaling system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>HTPCs generate extracellular adenosine and respond to adenosine via receptor\u2010mediated signaling, transcriptional remodeling, inflammatory signaling and steroidogenesis. If transferable to the in situ situation, adenosine is a multifunctional regulator of the peritubular compartment, involved in testicular homeostasis and male (in)fertility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70304","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:03:40Z","timestamp":1784016220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adenosine\u2014A Regulator of Human Testicular Peritubular Cells"],"prefix":"10.1111","author":[{"given":"Lina","family":"Scholz","sequence":"first","affiliation":[{"name":"Biomedical Center Munich Cell Biology, Anatomy III LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Liebich","sequence":"additional","affiliation":[{"name":"Biomedical Center Munich Cell Biology, Anatomy III LMU 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