The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli Cells
The blood–testis barrier (BTB) is formed from tight junctions (TJs) between Sertoli cells. This dynamic structure, which establishes an immune-privileged environment protecting haploid germ cells formed in puberty from cells of the innate immune system, protects male fertility. Testosterone produced...
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MDPI AG
2022-04-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/11/5/668 |
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| author | Hassan Kabbesh Ahmed Bulldan Lutz Konrad Georgios Scheiner-Bobis |
| author_facet | Hassan Kabbesh Ahmed Bulldan Lutz Konrad Georgios Scheiner-Bobis |
| author_sort | Hassan Kabbesh |
| collection | DOAJ |
| description | The blood–testis barrier (BTB) is formed from tight junctions (TJs) between Sertoli cells. This dynamic structure, which establishes an immune-privileged environment protecting haploid germ cells formed in puberty from cells of the innate immune system, protects male fertility. Testosterone produced in Leydig cells is one of the main regulators of TJ protein expression and BTB dynamics. Nevertheless, although it has been assumed that testosterone effects on TJs and BTB are mediated through the classical androgen receptor (AR), newer results call the importance of this receptor into question. ZIP9, a recently identified androgen receptor of plasma membranes, mediates testosterone effects that promote the expression of TJ proteins and TJ formation in a rat Sertoli cell line that lacks the classical AR. Although these findings suggest that ZIP9 mediates these testosterone effects, participation of the classical AR in these events cannot be excluded. Here we used immortalized adult rat Sertoli cells that express both ZIP9 and AR and addressed the involvement of these receptors in the stimulation of TJ protein expression and TJ formation in response to testosterone and to the androgenic peptide IAPG that acts via ZIP9. We find that both testosterone and IAPG trigger the so-called non-classical signaling pathway of testosterone and stimulate the expression of TJ-associated proteins and TJ formation. Silencing classical AR expression had no effect on the responses, whereas silencing of ZIP9 expression completely blocked them. Our results demonstrate that ZIP9 is the sole androgen receptor involved in the regulation of TJ protein expression and TJ formation at the BTB. |
| first_indexed | 2024-03-10T03:19:53Z |
| format | Article |
| id | doaj.art-e336eea712164cea8573630e2ba285f6 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T03:19:53Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-e336eea712164cea8573630e2ba285f62023-11-23T10:06:45ZengMDPI AGBiology2079-77372022-04-0111566810.3390/biology11050668The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli CellsHassan Kabbesh0Ahmed Bulldan1Lutz Konrad2Georgios Scheiner-Bobis3Institute for Veterinary Physiology and Biochemistry, School of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Str., D-35392 Giessen, GermanyInstitute for Veterinary Physiology and Biochemistry, School of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Str., D-35392 Giessen, GermanyCenter of Gynecology and Obstetrics, Faculty of Medicine, Justus-Liebig-University Giessen, Feulgenstr. 10-12, D-35392 Giessen, GermanyInstitute for Veterinary Physiology and Biochemistry, School of Veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Str., D-35392 Giessen, GermanyThe blood–testis barrier (BTB) is formed from tight junctions (TJs) between Sertoli cells. This dynamic structure, which establishes an immune-privileged environment protecting haploid germ cells formed in puberty from cells of the innate immune system, protects male fertility. Testosterone produced in Leydig cells is one of the main regulators of TJ protein expression and BTB dynamics. Nevertheless, although it has been assumed that testosterone effects on TJs and BTB are mediated through the classical androgen receptor (AR), newer results call the importance of this receptor into question. ZIP9, a recently identified androgen receptor of plasma membranes, mediates testosterone effects that promote the expression of TJ proteins and TJ formation in a rat Sertoli cell line that lacks the classical AR. Although these findings suggest that ZIP9 mediates these testosterone effects, participation of the classical AR in these events cannot be excluded. Here we used immortalized adult rat Sertoli cells that express both ZIP9 and AR and addressed the involvement of these receptors in the stimulation of TJ protein expression and TJ formation in response to testosterone and to the androgenic peptide IAPG that acts via ZIP9. We find that both testosterone and IAPG trigger the so-called non-classical signaling pathway of testosterone and stimulate the expression of TJ-associated proteins and TJ formation. Silencing classical AR expression had no effect on the responses, whereas silencing of ZIP9 expression completely blocked them. Our results demonstrate that ZIP9 is the sole androgen receptor involved in the regulation of TJ protein expression and TJ formation at the BTB.https://www.mdpi.com/2079-7737/11/5/668androgen receptorSertoli cellstestosteroneandrogenic peptideErk1/2CREB |
| spellingShingle | Hassan Kabbesh Ahmed Bulldan Lutz Konrad Georgios Scheiner-Bobis The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli Cells Biology androgen receptor Sertoli cells testosterone androgenic peptide Erk1/2 CREB |
| title | The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli Cells |
| title_full | The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli Cells |
| title_fullStr | The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli Cells |
| title_full_unstemmed | The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli Cells |
| title_short | The Role of ZIP9 and Androgen Receptor in the Establishment of Tight Junctions between Adult Rat Sertoli Cells |
| title_sort | role of zip9 and androgen receptor in the establishment of tight junctions between adult rat sertoli cells |
| topic | androgen receptor Sertoli cells testosterone androgenic peptide Erk1/2 CREB |
| url | https://www.mdpi.com/2079-7737/11/5/668 |
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