New insights into melatonin/CRH signaling in hamster Leydig cells
We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig ce...
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2012
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00166480_v178_n1_p153_Rossi http://hdl.handle.net/20.500.12110/paper_00166480_v178_n1_p153_Rossi |
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paper:paper_00166480_v178_n1_p153_Rossi2023-06-08T14:38:19Z New insights into melatonin/CRH signaling in hamster Leydig cells Androgens CRH Hamster Leydig cells MAP kinases Melatonin Transcription factors Tyrosine phosphatases androstanediol corticotropin releasing factor corticotropin releasing factor receptor melatonin melatonin 1 receptor melatonin receptor mitogen activated protein kinase protein c fos protein c jun protein tyrosine phosphatase steroidogenic acute regulatory protein stress activated protein kinase testosterone adult animal androgen synthesis animal cell animal tissue article colorimetry controlled study down regulation enzyme activation enzyme phosphorylation hormone inhibition human human tissue Leydig cell male male infertility nonhuman priority journal protein expression reverse transcription polymerase chain reaction signal transduction steroidogenesis Syrian hamster testis biopsy Western blotting We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17β-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process. © 2012 Elsevier Inc. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00166480_v178_n1_p153_Rossi http://hdl.handle.net/20.500.12110/paper_00166480_v178_n1_p153_Rossi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Androgens CRH Hamster Leydig cells MAP kinases Melatonin Transcription factors Tyrosine phosphatases androstanediol corticotropin releasing factor corticotropin releasing factor receptor melatonin melatonin 1 receptor melatonin receptor mitogen activated protein kinase protein c fos protein c jun protein tyrosine phosphatase steroidogenic acute regulatory protein stress activated protein kinase testosterone adult animal androgen synthesis animal cell animal tissue article colorimetry controlled study down regulation enzyme activation enzyme phosphorylation hormone inhibition human human tissue Leydig cell male male infertility nonhuman priority journal protein expression reverse transcription polymerase chain reaction signal transduction steroidogenesis Syrian hamster testis biopsy Western blotting |
| spellingShingle |
Androgens CRH Hamster Leydig cells MAP kinases Melatonin Transcription factors Tyrosine phosphatases androstanediol corticotropin releasing factor corticotropin releasing factor receptor melatonin melatonin 1 receptor melatonin receptor mitogen activated protein kinase protein c fos protein c jun protein tyrosine phosphatase steroidogenic acute regulatory protein stress activated protein kinase testosterone adult animal androgen synthesis animal cell animal tissue article colorimetry controlled study down regulation enzyme activation enzyme phosphorylation hormone inhibition human human tissue Leydig cell male male infertility nonhuman priority journal protein expression reverse transcription polymerase chain reaction signal transduction steroidogenesis Syrian hamster testis biopsy Western blotting New insights into melatonin/CRH signaling in hamster Leydig cells |
| topic_facet |
Androgens CRH Hamster Leydig cells MAP kinases Melatonin Transcription factors Tyrosine phosphatases androstanediol corticotropin releasing factor corticotropin releasing factor receptor melatonin melatonin 1 receptor melatonin receptor mitogen activated protein kinase protein c fos protein c jun protein tyrosine phosphatase steroidogenic acute regulatory protein stress activated protein kinase testosterone adult animal androgen synthesis animal cell animal tissue article colorimetry controlled study down regulation enzyme activation enzyme phosphorylation hormone inhibition human human tissue Leydig cell male male infertility nonhuman priority journal protein expression reverse transcription polymerase chain reaction signal transduction steroidogenesis Syrian hamster testis biopsy Western blotting |
| description |
We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17β-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process. © 2012 Elsevier Inc. |
| title |
New insights into melatonin/CRH signaling in hamster Leydig cells |
| title_short |
New insights into melatonin/CRH signaling in hamster Leydig cells |
| title_full |
New insights into melatonin/CRH signaling in hamster Leydig cells |
| title_fullStr |
New insights into melatonin/CRH signaling in hamster Leydig cells |
| title_full_unstemmed |
New insights into melatonin/CRH signaling in hamster Leydig cells |
| title_sort |
new insights into melatonin/crh signaling in hamster leydig cells |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00166480_v178_n1_p153_Rossi http://hdl.handle.net/20.500.12110/paper_00166480_v178_n1_p153_Rossi |
| _version_ |
1768545310705975296 |