Involvement of D-Aspartic acid in the synthesis of testosterone in rat testes

D'Aniello, Autimo; Cosmo, Anna Di; Cristo, Carlo Di; Annunziato, Lucio; Petrucelli, Leonard; Fisher, G. H.

doi:10.1016/0024-3205(96)00266-4

Cited by 176 publications

(131 citation statements)

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“…S3). DR and D-aspartate also are highly expressed in elongate spermatids of the testes (10,21). Besides its prominence in the developing nervous system, Daspartate is also expressed in the adult dentate gyrus.…”

Section: Resultsmentioning

confidence: 94%

“…Deletion of serine racemase alters NMDA receptor neurotransmission and long-term potentiation (2)(3)(4), and its disturbance has been implicated in schizophrenia (5)(6)(7). D-aspartate is present in selected neuronal populations in the brain as well as in neuroendocrine tissues, such as the catecholaminergic cells of the adrenal medulla, the anterior/posterior lobes of the pituitary gland, the pineal gland, and the testes (8)(9)(10). In early neonatal stages, high D-aspartate densities in the cortical plate, subventricular zone, and discrete portions of the hippocampal formation imply a developmental role (11).…”

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confidence: 99%

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Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis

Kim

Duan

Huang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

131

128

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D-Aspartic acid is abundant in the developing brain. We have identified and cloned mammalian aspartate racemase (DR), which converts Laspartate to D-aspartate and colocalizes with D-aspartate in the brain and neuroendocrine tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin RNA in newborn neurons of the adult hippocampus elicits profound defects in the dendritic development and survival of newborn neurons and survival. Because D-aspartate is a potential endogenous ligand for NMDA receptors, the loss of which elicits a phenotype resembling DR depletion, D-aspartate may function as a modulator of adult neurogenesis.neuronal development | neural progenitor cells | hippocampus | NMDA receptor | neuroendocrine D -amino acids are being increasingly recognized as putative neurotransmitters. D-serine, an endogenous ligand for the glutamate-NMDA receptor, is formed by serine racemase, a pyridoxal 5′-phosphate (PLP)-dependent enzyme that converts L-serine to D-serine (1). Deletion of serine racemase alters NMDA receptor neurotransmission and long-term potentiation (2-4), and its disturbance has been implicated in schizophrenia (5-7). D-aspartate is present in selected neuronal populations in the brain as well as in neuroendocrine tissues, such as the catecholaminergic cells of the adrenal medulla, the anterior/posterior lobes of the pituitary gland, the pineal gland, and the testes (8-10). In early neonatal stages, high D-aspartate densities in the cortical plate, subventricular zone, and discrete portions of the hippocampal formation imply a developmental role (11). In adult hippocampus, D-aspartate persists in dentate gyrus, where new neurons are generated throughout life (12, 13). These newborn neurons are integrated into existing neural circuitry and are involved in learning and memory formation (12, 13). Insight into specific neural functions for D-aspartate has been hampered by ignorance of its biosynthesis. In the present study, we identify and clone mammalian aspartate racemase (DR), which converts L-aspartate to D-aspartate. Deletion of DR leads to pronounced defects in adult hippocampal neurogenesis, implicating D-aspartate as a major regulator of neuronal development. Results and DiscussionCloning and Characterization of DR. In a genomic sequence analysis, we were unable to find candidate mammalian DR genes based on homology to serine racemase or bacterial aspartate racemases, which are either PLP-independent or PLP-dependent enzymes (14, 15). Vacca and coworkers (16-18) demonstrated that glutamate-oxalacetate transaminase (GOT) can generate small amounts of D-aspartate in the process of transaminating Laspartate to L-glutamate, and that formation of D-aspartate is augmented in GOT mutants, wherein histidine replaces tryptophan-140 and lysine replaces arginine-292. Tryptophan-140 normally prevents access of a proton donor, such as a water molecule, which can effectuate racemization (Fig. 1A); however, replacement of tryptophan-140 by histidine allows direct protonation by histidine for ...

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Section: Resultsmentioning

confidence: 94%

mentioning

confidence: 99%

Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis

Kim

Duan

Huang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

131

128

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“…For instance, d-aspartate accumulates over time in PC12 cell cultures (Long et al, 1998) and is synthesized from l-aspartate in primary neuronal cultures . d-Aspartate was shown to influence the secretion of several hormones, such as growth and luteinizing hormones, testosterone, melatonin and oxytocin (D'Aniello et al, 1996;Ishio et al, 1998;Nagata et al, 1999;D'Aniello et al, 2000;Wang et al, 2000). Pharmacological studies have shown that d-serine activates NMDA receptor responses by binding to the "glycine site" of the receptor with identical or even higher affinity than the co-agonist glycine (Danysz et al, 1990;Matsui et al, 1995;Danysz and Parsons, 1998).…”

Section: Introductionmentioning

confidence: 99%

Neurobiology through the looking-glass: d-serine as a new glial-derived transmitter

Wolosker

Panizzutti

Miranda

2002

Neurochemistry International

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“…DAA appears to have an important neuroendocrine role that may impact testosterone levels due to its ability to stimulate the release of sex hormones from the pituitary gland and testes in animals. An in vitro experiment from over a decade ago, involving the incubation of DAA with isolated rat testes, demonstrated that DAA induces the synthesis of testosterone [99]. In vivo experiments in this study, consisting of an intraperitonial injection of DAA in adult male rats, demonstrated that this amino acid accumulates in both the pituitary gland and testis (after 5 h, the accumulation was of 12-and 4-fold over basal values, respectively).…”

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confidence: 82%

Increasing Circulating Testosterone: Impact of Herbal Dietary Supplements

Gunnels¹

2014

J Plant Biochem Physiol

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Low circulating testosterone levels can present numerous problems related to the overall health and well-being of individuals, men in particular. This finding is well-documented in the literature and low testosterone appears more prevalent in older men, in particular those who are physically inactive and who present with elevated levels of body fat. Multiple botanical (herbal) products have been claimed to elevate circulating testosterone in men; however, data pertaining to the use of such herbal preparations obtained from human clinical trials are limited. This review examines the research to date pertaining to the use of herbal ingredients with regards to their ability to elevate blood testosterone levels. A collective summary of the findings indicate that certain herbal supplements may actually yield an increase in testosterone (e.g., Longjack root), while most others have little to no evidence in support of their use in human subjects. Additional, well-controlled clinical trials are needed to generate data relative to the use of herbal dietary supplements to increase circulating testosterone. Testosterone is generally measured as either "free" (unbound) or "total" (unbound and chemically bound). Men who have a morning serum testosterone level < 300 ng/dL are considered to be "low" and may be a candidate for testosterone replacement therapy-which has become more common in recent years due to the increased diagnosis of andropause [55]. Insufficient levels of testosterone due to either impaired production or uptake can present serious health consequences due to the wide array of applications of testosterone within the human body. Areas including skeletal muscle health, muscular strength, and overall well-being/vitality seem to be significantly affected by testosterone status. Increasing Circulating Testosterone: Impact of Herbal Dietary SupplementsTrintThe role of testosterone in muscle growth has been investigated extensively in both humans and animals [56][57][58][59][60][61][62]. One study in men concluded that the testosterone-induced increase in muscle volume is due to muscle fiber hypertrophy [63]. A follow-up study conducted a year later noted muscle hypertrophy in men over a period of 20 weeks of treatment with a gonadotropin-releasing hormone agonist and a 125-, 300-, or 600-mg weekly dose of testosterone enanthate. The main findings from this study indicated that testosterone administration was associated with a significant increase in myonuclear number in men receiving the 300-and 600-mg doses.Muscular strength is another important factor that has been shown to be affected by testosterone levels in the body [56,61,62,[64][65][66]. A recent investigation utilized 267 men with stages 2-4 of Chronic Kidney Disease to assess the impact of testosterone level on a variety of variables [64]. This study found that testosterone was significantly and independently associated with handgrip strength, muscle mass, and nutritional status as the disease progressed. Another study explored short-term testoste...

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Involvement of D-Aspartic acid in the synthesis of testosterone in rat testes

Cited by 176 publications

References 13 publications

Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis

Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis

Neurobiology through the looking-glass: d-serine as a new glial-derived transmitter

Increasing Circulating Testosterone: Impact of Herbal Dietary Supplements

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