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Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia

A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spe...

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Autores principales: Di Fiore, Maria Maddalena, Santillo, Alessandra, Falvo, Sara, Longobardi, Salvatore, Chieffi Baccari, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964501/
https://www.ncbi.nlm.nih.gov/pubmed/27428949
http://dx.doi.org/10.3390/ijms17071127
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author Di Fiore, Maria Maddalena
Santillo, Alessandra
Falvo, Sara
Longobardi, Salvatore
Chieffi Baccari, Gabriella
author_facet Di Fiore, Maria Maddalena
Santillo, Alessandra
Falvo, Sara
Longobardi, Salvatore
Chieffi Baccari, Gabriella
author_sort Di Fiore, Maria Maddalena
collection PubMed
description A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA) and aurora kinase B (AURKB). Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor β (ESR2) interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation.
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spelling pubmed-49645012016-08-03 Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia Di Fiore, Maria Maddalena Santillo, Alessandra Falvo, Sara Longobardi, Salvatore Chieffi Baccari, Gabriella Int J Mol Sci Review A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA) and aurora kinase B (AURKB). Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor β (ESR2) interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation. MDPI 2016-07-14 /pmc/articles/PMC4964501/ /pubmed/27428949 http://dx.doi.org/10.3390/ijms17071127 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Di Fiore, Maria Maddalena
Santillo, Alessandra
Falvo, Sara
Longobardi, Salvatore
Chieffi Baccari, Gabriella
Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia
title Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia
title_full Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia
title_fullStr Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia
title_full_unstemmed Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia
title_short Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia
title_sort molecular mechanisms elicited by d-aspartate in leydig cells and spermatogonia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964501/
https://www.ncbi.nlm.nih.gov/pubmed/27428949
http://dx.doi.org/10.3390/ijms17071127
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