α-Adrenergic receptor antagonism and N-methyl-D-aspartate (NMDA) induced luteinizing hormone release in female rhesus macaques

Henryk Urbanski, Vasilios T. Garyfallou, Steven Kohama, David Hess

    Research output: Contribution to journalArticle

    22 Citations (Scopus)

    Abstract

    The stimulatory influence of N-methyl-D-aspartate (NMDA), a glutamate receptor agonist, on LH secretion is well established in several mammalian species including the rhesus macaque. Although the mechanism of excitation appears to involve enhanced GnRH secretion, it is unclear whether the GnRH neurons respond directly to this excitation or whether stimulatory inter-neurons are involved. This study investigated the possibility that noradrenergic afferents play a major role in mediating the response of the primate hypothalamo-pituitary reproductive axis to NMDA. In situ hybridization histochemistry, using a cRNA probe coding for the NMDAR1 receptor subunit, revealed abundant mRNA in the locus coeruleus, a brain area rich in noradrenergic neurons. Furthermore, using double-label fluorescence immunocytochemistry, the tyrosine hydroxylase immunopositive neurons of the locus coeruleus showed immunoreactivity for the NMDAR1 receptor subunit protein. A second experiment examined whether prazosin, an α-adrenergic receptor antagonist, could attenuate NMDA-induced stimulation of LH release. Prazosin (either 1 or 5 mg/kg b.wt., i.v.) was administered to female rhesus macaques during the luteal phase of the menstrual cycle, 40 min before administration of NMDA (10 mg/kg b.wt., i.v.). Regardless of the prazosin pre-treatment, plasma LH concentrations showed a significant increase (P <0.01) within 10 min of the administration of NMDA. Therefore, in spite of the evidence that at least some of the noradrenergic neurons of the primate hindbrain express the NMDAR1 receptor subunit, it is unlikely that noradrenergic inter-neuronal pathways alone play a major role in mediating the stimulators action of NMDA on GnRH/LH secretion in primates. Indeed, because the GNRH neurons of the rhesus macaque are located diffusely in various regions of the hypothalamus and medial-septal/preoptic area, their net response to excitatory amino acids is likely to be more complicated, involving a combination of both stimulatory and inhibitory inter-neurons, and possibly also a direct interaction.

    Original languageEnglish (US)
    Pages (from-to)96-104
    Number of pages9
    JournalBrain Research
    Volume744
    Issue number1
    DOIs
    StatePublished - Jan 2 1997

    Fingerprint

    N-Methylaspartate
    Luteinizing Hormone
    Macaca mulatta
    Adrenergic Receptors
    Prazosin
    Neurons
    Gonadotropin-Releasing Hormone
    Primates
    Adrenergic Neurons
    Locus Coeruleus
    Septum of Brain
    Excitatory Amino Acid Agonists
    Complementary RNA
    Rhombencephalon
    Excitatory Amino Acids
    Adrenergic Antagonists
    Preoptic Area
    Luteal Phase
    Protein Subunits
    Glutamate Receptors

    Keywords

    • glutamate
    • GnRH
    • idazoxan
    • locus coeruleus
    • prazosin

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    α-Adrenergic receptor antagonism and N-methyl-D-aspartate (NMDA) induced luteinizing hormone release in female rhesus macaques. / Urbanski, Henryk; Garyfallou, Vasilios T.; Kohama, Steven; Hess, David.

    In: Brain Research, Vol. 744, No. 1, 02.01.1997, p. 96-104.

    Research output: Contribution to journalArticle

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    abstract = "The stimulatory influence of N-methyl-D-aspartate (NMDA), a glutamate receptor agonist, on LH secretion is well established in several mammalian species including the rhesus macaque. Although the mechanism of excitation appears to involve enhanced GnRH secretion, it is unclear whether the GnRH neurons respond directly to this excitation or whether stimulatory inter-neurons are involved. This study investigated the possibility that noradrenergic afferents play a major role in mediating the response of the primate hypothalamo-pituitary reproductive axis to NMDA. In situ hybridization histochemistry, using a cRNA probe coding for the NMDAR1 receptor subunit, revealed abundant mRNA in the locus coeruleus, a brain area rich in noradrenergic neurons. Furthermore, using double-label fluorescence immunocytochemistry, the tyrosine hydroxylase immunopositive neurons of the locus coeruleus showed immunoreactivity for the NMDAR1 receptor subunit protein. A second experiment examined whether prazosin, an α-adrenergic receptor antagonist, could attenuate NMDA-induced stimulation of LH release. Prazosin (either 1 or 5 mg/kg b.wt., i.v.) was administered to female rhesus macaques during the luteal phase of the menstrual cycle, 40 min before administration of NMDA (10 mg/kg b.wt., i.v.). Regardless of the prazosin pre-treatment, plasma LH concentrations showed a significant increase (P <0.01) within 10 min of the administration of NMDA. Therefore, in spite of the evidence that at least some of the noradrenergic neurons of the primate hindbrain express the NMDAR1 receptor subunit, it is unlikely that noradrenergic inter-neuronal pathways alone play a major role in mediating the stimulators action of NMDA on GnRH/LH secretion in primates. Indeed, because the GNRH neurons of the rhesus macaque are located diffusely in various regions of the hypothalamus and medial-septal/preoptic area, their net response to excitatory amino acids is likely to be more complicated, involving a combination of both stimulatory and inhibitory inter-neurons, and possibly also a direct interaction.",
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