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Activation of GR by dexamethasone (Dex) strongly influences the phenotype of cultured human testicular peritubular cells (HTPCs), causing massive changes of their proteome and secretome. As glucocorticoids (GC) are also known to set the internal clock of peripheral organs by regulating clock genes, we tested such an influence of Dex in HTPCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed cellular studies with HTPCs and immortalized nonhuman primate (\n                      <jats:italic>Callithrix jacchus; Cj<\/jats:italic>\n                      )\u2010derived peritubular cells, organotypic incubations of testicular fragments of\n                      <jats:italic>Cj<\/jats:italic>\n                      , qPCR and proteomic, as well as immunohistochemical studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Basal clock gene expression levels, when monitored by qPCR under standard culture conditions, showed alterations over 24 h, suggesting an endogenous circadian rhythm, especially for\n                      <jats:italic>BMAL1<\/jats:italic>\n                      . Dex (1 \u00b5M) when added to cells, caused a strong and significant increase of\n                      <jats:italic>PER1<\/jats:italic>\n                      , followed by elevations of\n                      <jats:italic>BMAL1<\/jats:italic>\n                      , and other clock genes. This action was observed as early as 4 h after the addition of Dex. Immunohistochemistry and data mining revealed GR in testicular peritubular cells and other somatic cells of\n                      <jats:italic>Cj<\/jats:italic>\n                      , in situ. We therefore performed organotypic incubations of testicular fragments of\n                      <jats:italic>Cj<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      = 3) and found that upon addition of Dex (1 \u00b5M), mRNA levels of\n                      <jats:italic>BMAL1<\/jats:italic>\n                      and\n                      <jats:italic>PER1<\/jats:italic>\n                      also increased in samples of two out of three animals after 6 h. Mass spectrometry did, however, not reveal significant alterations of the testicular proteome, possibly due to the short time point and\/or the fact that the somatic GR\u2010expressing cells represent only a small portion of the testis. In support for this assumption, Dex (1 \u00b5M; 6 h) significantly increased mRNA levels of\n                      <jats:italic>BMAL1<\/jats:italic>\n                      and\n                      <jats:italic>PER1<\/jats:italic>\n                      in\n                      <jats:italic>Cj<\/jats:italic>\n                      \u2010derived immortalized testicular peritubular cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results indicate that an internal clock system likely exists in peritubular cells of the testis and that Dex, via testicular GR expressed by peritubular cells and other somatic cells, is a strong regulator of this system. In a physiological situation, GC thus may be important regulators of the testicular clock, while in a situation of prolonged stress or GC\u2010medication, derangements in clock gene expression may result.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13788","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T23:50:23Z","timestamp":1730937023000},"page":"1970-1979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dexamethasone is a regulator of clock genes in testicular peritubular cells"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6486-1170","authenticated-orcid":false,"given":"Harald","family":"Welter","sequence":"first","affiliation":[{"name":"Biomedical Center Cell Biology, Anatomy III Faculty of Medicine Ludwig Maximilian University of Munich, Planegg\u2010Martinsried  Munich 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