Comparison of the Effects of N-Methyl-DL-Aspartic Acid on Gonadotropin and Prolactin Secretion in Anestrous Mares and Mares Exhibiting Estrous Cycles during Anestrus1

Fitzgerald, B. P.; Davison, Laurie A.

doi:10.1095/biolreprod57.1.36

Cited by 18 publications

(5 citation statements)

References 46 publications

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“…To identify the mechanism(s) by which D-Asp elicits hormone release, we were intrigued by the structural similarities between D-Asp and its methylated derivative NMDA, hypothesizing that the latter excitatory amino acid could be present in neuroendocrine animal tissues arising from the endogenous D-Asp. This hypothesis was suggested by the widely documented ability of NMDA to elicit the release of GnRH from the hypothalamus (34,37,43,50) as well as the secretion of adenohypophysial hormones in rat (26 -28, 31-33, 35, 38, 42-43, 49), rhesus monkey (29 -30), sheep (36), pig (40), rainbow trout (47), barrow (44), ewe (45), mares (46), gilts (48), ovine fetus (50), and pig cultured cells (41). Using two sensitive and specific fluorometric methods devised in this work, we were able to demonstrate that NMDA is actually present in the rat neuroendocrine system at levels comparable to those of many known hormones of the hypothalamus-hypophysis axis.…”

Section: Discussionmentioning

confidence: 99%

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

D‧Aniello¹,

et al. 2000

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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 approximately 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-adenosylmethionine-dependent enzyme, which we tentatively denominated as NMDA synthase.

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Section: Discussionmentioning

confidence: 99%

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

D‧Aniello¹,

et al. 2000

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“…In cycling mare ( Equus caballus ), the response to NMA (1 mg/kg b.w.) was dependent on the stage of the estrus cycle, and a significantly higher proportion of individuals in the luteal phase responded to NMA treatment compared to those in the follicular phase [87]. In anestrous and cycling mares, NMA suppressed the secretion of PRL, which would normally be observed during the non-breeding season.…”

Section: Livestock Animalsmentioning

confidence: 99%

“…In anestrous and cycling mares, NMA suppressed the secretion of PRL, which would normally be observed during the non-breeding season. Therefore, differences in reproductive activity in mares during the non-breeding season are unlikely to reflect a change in the glutamatergic activity, and the effects of NMA on LH release depend on the stage of the estrus cycle and the circulating steroidal milieu [87].…”

Section: Livestock Animalsmentioning

confidence: 99%

D-Aspartic Acid in Vertebrate Reproduction: Animal Models and Experimental Designs ‡

et al. 2019

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This article reviews the animal models and experimental designs that have been used during the past twenty years to demonstrate the prominent role played by D-aspartate (D-Asp) in the reproduction of vertebrates, from amphibians to humans. We have tabulated the findings of in vivo and in vitro experiments that demonstrate the effects of D-Asp uptake on hormone production and gametogenesis in vertebrate animal models. The contribution of each animal model to the existing knowledge on the role of D-Asp in reproductive processes has been discussed. A critical analysis of experimental designs has also been carried out. Experiments performed on wild animal species suggest a role of D-Asp in the mechanisms that regulate the reproductive cycle. Several in vivo and in vitro studies carried out on mouse and rat models have facilitated an understanding of the molecular pathways activated by D-Asp in both steroidogenesis and spermatogenesis, with particular emphasis on testosterone biosynthesis. Some attempts using D-Asp for the improvement of reproductive activity in animals of commercial interest have yielded mixed results. The increased transcriptome activity of enzymes and receptors involved in the reproductive activity in D-Asp-treated broiler roosters revealed further details on the mechanism of action of D-Asp on the reproductive processes. The close relationship between D-Asp and reproductive activity has emerged, particularly in relation to its effects exerted on semen quality, proposing therapeutic applications of this amino acid in andrology and in medically-assisted procreation techniques.

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“…Although horses are seasonal breeders, a small percentage of mares continue to exhibit ovarian activity throughout the nonbreeding season [1][2][3]. Among these mares, it has been shown [2] that there is no discernible pattern in the occurrence or absence of unseasonal cyclicity from one year to the next.…”

Section: Introductionmentioning

confidence: 99%

“…2 Correspondence. FAX: 606 257 8542; e-mail: ldavison@pop.uky.edu a possible cause for continuation of estrous cycles has also been suggested; however, no differences were observed between anestrous and cycling mares in gonadotropin response to the glutamatergic agonist N-methyl-D,L-aspartic acid during the nonbreeding season [3]. In view of this consideration, the present study investigated the hypotheses that the occurrence of estrous cycles during the nonbreeding season reflects reduced opioidergic activity on GnRH/ gonadotropin secretion compared with observations in anestrous mares and that opioid tone among these mares would resemble that of mares during the breeding season.…”

Section: Introductionmentioning

confidence: 99%

Gonadotropin Response to Naloxone in the Mare: Effect of Time of Year and Reproductive Status1

Davison¹,

McManus²,

Fitzgerald³

1998

Biology of Reproduction

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In the mare, endogenous opioids have been implicated in the suppression of gonadotropin secretion during seasonal anestrus (AN). The present study tested whether continuation of reproductive activity during the nonbreeding season (NBS) reflects the absence of a seasonal shift in opioid tone compared to what occurs in AN mares. During the NBS, 11 AN and 8 luteal-phase mares received 0.1, 0.05, 0. 025 mg/kg naloxone (NAL) or vehicle on alternate days. Whereas cycling mares responded to all dosages of NAL, AN mares responded only to the higher dosages for FSH, and LH failed to increase at any dosage employed. During the breeding season (BS), the response to these dosages of NAL was reevaluated in 12 mares in the luteal phase of a synchronized estrous cycle. Although there was no difference between cycling mares during the breeding and nonbreeding seasons in FSH response, those mares that had cycled during the NBS showed a greater LH response to 0.05 mg/kg NAL than mares during the BS. From these data, we conclude that opioid tone is lower during the BS than during AN and that this shift in inhibitory tone does not occur in mares that cycle during the NBS. Thus, reduced opioid tone may play a role in the mechanisms controlling the nonseasonal exhibition of estrous cycles in the mare.

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Comparison of the Effects of N-Methyl-DL-Aspartic Acid on Gonadotropin and Prolactin Secretion in Anestrous Mares and Mares Exhibiting Estrous Cycles during Anestrus1

Cited by 18 publications

References 46 publications

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

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

D-Aspartic Acid in Vertebrate Reproduction: Animal Models and Experimental Designs ‡

Gonadotropin Response to Naloxone in the Mare: Effect of Time of Year and Reproductive Status1

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