Endogenous Excitatory Amino Acid Neurotransmission Regulates the Estradiol-Induced Lh Surge in Ovariectomized Rats

López, Francisco J.; Donoso, Alfredo O.; Negro‐Vilar, A.

doi:10.1210/endo-126-3-1771

Cited by 115 publications

(57 citation statements)

References 19 publications

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“…This hypothesis is supported by previous studies showing that, in the afternoon of proestrus, nearly half of activated GnRH neurons express kainate receptor subunits (62). In addition, the AMPA/kainate receptor antagonist DNQX can block the estradiol-induced LH surge in ovariectomized rats (63).…”

Section: Sex Steroid Interaction With Glutamate Receptor-mediated Relsupporting

confidence: 75%

Control of Puberty by Excitatory Amino Acid Neurotransmitters and its Clinical Implications

Parent

Matagne

Bourguignon

2005

ENDO

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Excitatory amino acids, glutamate in particular, have a marked stimulatory effect on the reproductive axis, particulary at puberty. Glutamate, N-methyl-D-aspartate (NMDA), and kainite-stimulate gonadotropin-releasing hormone (GnRH) secretion in immature mammals and NMDA receptor stimulation results in precocious puberty in rats and monkeys. Puberty is characterized by an increased sensitivity of GnRH to glutamate as well as an increase in glutaminase activity in the hypothalamus. Glutamatergic and GABAergic regulation of GnRH secretion seem strongly interdependent around puberty. In addition to the transsynaptic glutamatergic regulation of GnRH secretion, a coordinated activity of glutamatergic neurons and astroglial cells has been shown to play an active role in puberty. The participation of kainate receptors in the estradiol-induced advancement of puberty suggest that these receptors may be involved in the estradiol-mediated activation of GnRH secretion at puberty. A case of precocious puberty associated with hyperglycinemia illustrates the NMDA involvement in puberty in humans. In this patient, the occurrence of precocious puberty was thought to result from excessive stimulation by glycine of the NMDA receptors linked to the GnRH neurons. Glutamate plays several roles in the hypothalamic mechanism of puberty as it has been shown in animal models, but there are still few clinical data supporting the role of glutamate in human puberty.

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Section: Sex Steroid Interaction With Glutamate Receptor-mediated Relsupporting

confidence: 75%

Control of Puberty by Excitatory Amino Acid Neurotransmitters and its Clinical Implications

Parent

Matagne

Bourguignon

2005

ENDO

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“…223). Studies employing the pharmacological blockade of the N-methyl-d-aspartate (NMDA), dl-␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate receptors have shown that glutamate and aspartate play a role in generating both the pulsatile (224) and surge (225)(226)(227) modes of GnRH/LH secretion in the adult female rat. Hence, it seems highly likely that neurons utilizing excitatory amino acids are part of the GnRH network.…”

Section: Excitatory Amino Acidsmentioning

confidence: 99%

Multimodal Influence of Estrogen upon Gonadotropin-Releasing Hormone Neurons

1998

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“…Immunohistochemical localization has revealed the pattern of glutamate receptors in the hypothalamus, with NMDA type receptors mostly in the rostra1 regions and the non-NMDA type close to the median eminence (7). Convincing evidence that these excitatory mechanisms arc of physiological importance in the regulation of reproduction, comes from the observations that treatments with specific antagonists to glutamate receptors result in a decline in pulsatile LH secretion (8), blockage of oestradiol-induced LH secretion (9) and a delay in the onset of puberty (10, 1 I).…”

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confidence: 99%

Luteinizing Hormone Responses to N‐Methyl‐D,L‐Aspartate During a Photoperiodically‐lnduced Reproductive Cycle in the Ram

Lincoln

1991

J Neuroendocrinology

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Aspartate and glutamate represent a major class of excitatory amino-acid neurotransmitters in the vertebrate brain, and stimulation of glutaminergic receptors by the specific agonist N-methyl-D,L-aspartate (NMDA) induces luteinizing hormone-releasing hormone (LHRH) and LH secretion. In this study, we used NMDA as a probe to investigate the hypothalamic regulation of LH secretion at different stages of a reproductive cycle in Soay rams induced by exposure to alternating 16-week periods of long and short days. NMDA (20 mg/kg) injected intravenously caused an acute increase in blood plasma concentrations of LH, with a significant increase within 2 to 4 min, and peak levels within 20 min. The magnitude of the response changed markedly during the cycle; it was greatest in the sexually inactive phase under long days (with a linear dose-response over the range 1 to 20 mgikg NMDA) and least in the sexually active phase under short days (only 20 mg/kg NMDA produced a small response). Pituitary responsiveness to a standard dose of LHRH (5.3 ng/kg iv) varied only slightly at the different stages and could not account for the observed changes in the LH response to NMDA. There were the expected changes in the endogenous pattern of LH secretion during the cycle, with high frequency LH pulses occurring during the sexually active phase. There was an inverse relationship between the frequency of LH pulses and the LH response to NMDA. Pretreatment of rams with an LHRH antagonist (36 pg/kg iv; Syntex, RS18286) totally blocked the LH response to both NMDA and LHRH, while in a separate study, treatment with dexamethasone (synthetic glucocorticoid, 133.4 pglkg iv) partially blocked the LH responses. The overall results indicate that NMDA stimulates LHRH secretion in the ram and the response is independent of the activation of the hypothalamo-pituitary-adrenal axis. The variation in the LH response during the reproductive cycle may reflect changes in the releasable stores of LHRH in the median eminence. These appear to be depleted in the sexually active phase, when LHRH is secreted in pulses at high frequency. The variation in the response to NMDA may also reflect changes in release of endogenous excitatory amino-acids, which act via NMDA receptors to form part of the physiological regulation of the reproductive cycle in the ram.The dicarboxylic amino-acids aspartate and glutamate represent a major class of excitatory neurotransmitters in the vertebrate brain ( I ) . These amino-acids have excitatory effects through at least three classes of receptors of which the N-methyl-D,Laspartate (NMDA) receptor class is best characterized, and these receptors are apparently involved in the neural control of reproduction (2). Studies in the rat have shown that the administration of NMDA causes the release of luteinizing hormone (LH) from the anterior pituitary gland by inducing the secretion of LHreleasing hormone (LHRH) from the hypothalamus (3, 4), and there is evidence that both NMDA and non-NMDA excitatory amino-acid receptors are in...

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Endogenous Excitatory Amino Acid Neurotransmission Regulates the Estradiol-Induced Lh Surge in Ovariectomized Rats

Cited by 115 publications

References 19 publications

Control of Puberty by Excitatory Amino Acid Neurotransmitters and its Clinical Implications

Control of Puberty by Excitatory Amino Acid Neurotransmitters and its Clinical Implications

Multimodal Influence of Estrogen upon Gonadotropin-Releasing Hormone Neurons

Luteinizing Hormone Responses to N‐Methyl‐D,L‐Aspartate During a Photoperiodically‐lnduced Reproductive Cycle in the Ram

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