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pmid:39124625
Identification of Catecholamine and Drug Target α2A-Adrenoceptor in Human Testis and Human Testicular Peritubular Cells.
Welter Harald · Kreitmair Nicole · Schneider Michaela · Herrmann Carola · Schmid Nina · Stepanov Youli · Fröhlich Thomas · Köhn Frank-Michael · Pickl Ulrich · Trottmann Matthias · Mayerhofer Artur
Journal of clinical medicine · 2024 doi:10.3390/jcm13154357
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Complete file
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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 α2A-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 (1-1000 µM) 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 µM) on secreted IL6. When examined in collagen gel contraction assays of HTPCs, clonidine (10 µM) exerted a slight relaxing action, while a proteomic study revealed that clonidine (10 µM) 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.", "claims": [{"id": "claim-method", "statement": "Statistical analyses of qPCR and ELISA data were performed using GraphPad Prism 6.0 Software (GraphPad Software Inc., San Diego, CA, USA). qPCR data were analyzed via t-test of 2−ΔΔCq values, as were IL6 levels in the supernatant via one-sample t-tests of non-normalized values. Paired t-test was used to compare two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39124625", "locator": "sections[9] \"2.7. Statistical Analysis\" paragraph 2", "quote": "Statistical analyses of qPCR and ELISA data were performed using GraphPad Prism 6.0 Software (GraphPad Software Inc., San Diego, CA, USA). qPCR data were analyzed via t-test of 2−ΔΔCq values, as were IL6 levels in the supernatant via one-sample t-tests of non-normalized values. Paired t-test was used to compare two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD052220.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39124625", "locator": "sections[25] \"notes\" paragraph 1", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD052220."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Results revealed that only IL6 levels were significantly and more than twofold increased, while all others were unaffected by the 10 µM clonidine treatment for 24 h.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39124625", "locator": "sections[14] \"3.4. 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