d-Aspartic acid stimulates steroidogenesis through the delay of LH receptor internalization in a mammalian Leydig cell line

Nisio, Andrea Di; Toni, Luca De; Ferigo, Marco; Rocca, Maria Santa; Speltra, Elena; Ferlin, Alberto

doi:10.1007/s40618-015-0333-4

Cited by 14 publications

(11 citation statements)

References 26 publications

(28 reference statements)

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“…hCG via activation of adenylate cyclase activates the cAMP translocation of cholesterol to the inner mitochondrial membrane which is required for testosterone synthesis (33). Also they have shown that D-Asp and hCG synergistically up-regulate the production of testosterone in rat Leydig cells, apparently by increasing gene expression StAR in purified rat Leydig cells (31, 34, 45, 46). …”

Section: Resultsmentioning

confidence: 99%

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The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review

Roshanzamir¹,

Safavi²

2017

IJRM

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Background: D-Aspartic acid (D-Asp) is in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions. Recently, it has been reported that D-Asp is involved in the synthesis and release of testosterone and is assumed can be used as a testosterone booster for infertile men, and by athletes to increase muscle mass and strength. Objective: The aim of this review is to summarize available evidence related to the effects of D-Asp on serum testosterone levels. Materials and Methods: We conducted a systematic review of all type studies, which evaluated the effect of the D-Asp on blood testosterone including published papers until October 2015, using PubMed, ISI Web of Science, ProQuest and Scopus database. Results: With 396 retrieved records, 23 animal studies and 4 human studies were included. In vivo and in vitro animal studies revealed the effect of D-Asp depending on species, sex and organ-specific. Our results showed that exogenous D-Asp enhances testosterone levels in male animal's studies, whereas studies in human yielded inconsistent results. The evidence for this association in man is still sparse, mostly because of limited number and poor quality studies. Conclusion: There is an urgent need for more and well-designed human clinical trials with larger sample sizes and longer duration to investigate putative effects of D-Asp on testosterone concentrations.

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Section: Resultsmentioning

confidence: 99%

“…D-Asp is capable of boosting the action of human chorionic gonadotropin (hCG), thereby it is able to induce testosterone synthesis in the Leydig cells (34, 46). …”

Section: Discussionmentioning

confidence: 99%

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The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review

Roshanzamir¹,

Safavi²

2017

IJRM

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“…In the acute stimulatory phase, cholesterol is transported across the mitochondrial membrane, whereas the chronic effect of LH exposure enhances the expression of steroidogenic enzymes (Midzak et al 2009). Interestingly, Di Nisio et al (2016) reported DA delays LHR internalisation in murine Leydig cells incubated with human chorionic gonadotrophin, resulting in prolonged stimulation of steroidogenesis. Aside from the pivotal role of LHR in reproduction, mice lacking AR in Leydig cells were infertile due to the arrest of spermatogenesis at the spermatid stage and lower serum testosterone concentrations, leading to the reduction of several key steroidogenic enzymes, including 17b-HSD, 3b-HSD and P450scc, rather than changes in the number o f Sertoli cells (Xu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

D-Aspartate amends reproductive performance of aged roosters by changing gene expression and testicular histology

Ansari

Zhandi

Kohram

et al. 2018

Reprod. Fertil. Dev.

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Male broiler breeders (n = 32) of 55 weeks of age were administered four different doses of capsulated d-aspartate (DA; 0, 100, 200 or 300 mg kg−1 day−1, p.o. (DA0, DA100, DA200 and DA300 respectively)) for 12 successive weeks to assess reproductive performance, blood testosterone, testicular histology and transcript levels of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), androgen receptor (AR), LH receptor (LHR), 3β-hydroxysteroid dehydrogenase (3BHSD), proliferating cell nuclear antigen (PCNA), glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) and glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B). Blood samples and ejaculates were collected, and bodyweight was recorded weekly for 10 weeks. AI was performed weekly for the last 2 weeks to determine the number of sperm penetration holes in the perivitelline layer, fertility and hatchability. Testes histology and transcript levels were evaluated in the 12th week. Bodyweight, numbers of Leydig cells and blood vessels, testis index and levels of sperm abnormalities were not affected (P > 0.05) by the treatment. However, sperm total and forward motility, plasma membrane integrity and functionality of sperm, ejaculate volume, testosterone concentration and fertility were higher (P < 0.05) in both the DA200 and DA300 groups compared with the other groups. In the DA100 and DA200 groups, sperm concentration, number of spermatogonia, thickness of the seminiferous epithelium and the diameter of tubules were significantly higher (P < 0.05) than the other DA-treated groups. The number of penetration holes, hatchability and malondialdehyde concentration were higher in the DA200, all DA-treated and DA300 groups respectively compared with the control and other treatment groups. Except for P450scc, AR, LHR and PCNA transcript levels in the DA300 groups, the relative expression of the genes evaluated improved significantly in the other DA-treated groups. Based on these experimental findings, it is concluded that DA improves reproductive performance of aged roosters.

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“…Immature Leydig cells cultured with d -Asp showed significantly higher Star mRNA and protein levels as well as Cyp11a1 and Hsd3b1 mRNA levels relative to controls [ 37 ]. d -Asp, in the presence or in the absence of hCG, upregulated T production in rat Leydig cells by increasing the Star mRNA and protein expression [ 14 , 15 , 38 , 39 ].…”

Section: D -Asp and Leydig Cellsmentioning

confidence: 99%

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

Fiore¹,

Santillo²,

Falvo³

et al. 2016

IJMS

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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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d-Aspartic acid stimulates steroidogenesis through the delay of LH receptor internalization in a mammalian Leydig cell line

Cited by 14 publications

References 26 publications

The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review

The putative effects of D-Aspartic acid on blood testosterone levels: A systematic review

D-Aspartate amends reproductive performance of aged roosters by changing gene expression and testicular histology

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

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