Occurrence of D‐aspartic acid and N‐methyl‐D‐aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release
Abstract
Using two specific and sensitive fluorometric/HPLC methods and a GC‐MS method, alone and in combination with D‐aspartate oxidase, we have demonstrated for the first time that N‐methyl‐D‐aspartate (NMDA), in addition to D‐aspartate (D‐Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands. Both of these amino acids are mostly concentrated at nmol/g levels in the adenohypophysis, hypothalamus, brain, and testis. The adenohypophysis maximally showed the ability to accumulate D‐Asp when the latter is exogenously administered. In vivo experiments, consisting of the i.p. injection of D‐Asp, showed that D‐Asp induced both growth hormone and luteinizing hormone (LH) release. However, in vitro experiments showed that D‐Asp was able to induce LH release from adenohypophysis only when this gland was co‐incubated with the hypothalamus. This is because D‐Asp also induces the release of GnRH from the hypothalamus, which in turn is directly responsible for the D‐Asp‐induced LH secretion from the pituitary gland. Compared to D‐Asp, NMDA elicits its hormone release action at concentrations ~100‐fold lower than D‐Asp. D‐AP5, a specific NMDA receptor antagonist, inhibited D‐Asp and NMDA hormonal activity, demonstrating that these actions are mediated by NMDA receptors. NMDA is biosynthesized from D‐Asp by an S‐adeno‐sylmethionine‐dependent enzyme, which we tentatively denominated as NMDA synthase.—D‧Aniello, A., Di Fiore, M. M., Fisher, G. H., Milone, A., Seleni, A., D'Aniello, S., Perna, A. F., Ingrosso, D. Occurrence of D‐aspartic acid and N‐methyl‐D‐aspartic acid in rat neuroendocrine tissues and their role in the modulation of luteinizing hormone and growth hormone release. FASEB J. 14, 699–714 (2000)
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Associations between D-aspartic acid and testosterone or luteinizing hormone are largely based on animal studies.
“Nonetheless, these associations are largely based on animal studies.[Citation23–25]”
From Ergogenic properties, safety evaluation and regulations of selected ingredients in testosterone booster dietary supplements (2024) · cites this paper as [24]
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- Authors
- D‧Aniello, A., Di Fiore, M. M., Fisher, G. H., Milone, A., Seleni, A., D'Aniello, S., Perna, A. F., & Ingrosso, D.
- Affiliations
- Department of Biochemistry and Molecular Biology and Neurobiology Zoological Station ‘A. Dohrn’ Napoli 80121 Italy
- Department of Scienze della Vita Second University of Naples Caserta 81100 Italy
- Barry University (US)
- Istituto di Chimica Biomolecolare (IT)
- Department of Radioimmunology Laboratorio Igea Napoli Frattamaggiore 80027 Italy
- Federico II University Hospital (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2000-04
- Volume
- 14
- Issue
- 5
- Pages
- 699-714
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1884051840
- Cited by
- 227
- References
- 54
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 12 · 2018: 6 · 2017: 11 · 2016: 13 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 9
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NIGMS‐MBRS/SCORE SO6GM45455, FIC‐MIRT GMTW00033)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- D-aspartic acid, N-methyl-D-aspartate, NMDA receptor, luteinizing hormone secretion, growth hormone secretion, anterior pituitary, hypothalamus, gonadotropin-releasing hormone, S-adenosylmethionine, neuroendocrine regulation, D-AP5, rats
- MeSH terms
- Animals, Aspartic Acid, Circadian Rhythm, Hypothalamus, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Neurosecretory Systems, Pituitary Gland, Anterior, Growth Hormone, Tissue Distribution, N-Methylaspartate, Rats, Wistar, Rats, In Vitro Techniques
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