EXCITATORY AMINO ACIDS AND THE CONTROL OF REPRODUCTION

    Project: Research project

    Description

    Approximately 16% of US couples remain involuntarily childless or
    experience major fertility problems. Although amenorrhea appears to be
    one of the principal causes of human infertility, the underlying
    neuroendocrine pathways responsible for its occurrence are poorly
    understood. On the other hand, it is already well established that
    luteinizing hormone-releasing hormone (LHRH) acts as the primary
    neuroendocrine link between the central nervous system and the rest of
    the reproductive axis. Consequently, a deeper understanding of the
    neural circuitry that controls the pulsatile and surge patterns of LHRH
    secretion should help to elucidate the underlying causes of centrally-
    originating reproductive disorders. In the proposed study, a series of
    non-invasive experiments will be performed to provide evidence that
    excitatory amino acid (EAA) receptors play a major role in the control
    of LHRH neuronal function. The results are expected to demonstrate the
    EAA receptors are critically involved in the generation and modulation
    of pulsatile LHRH secretion (Specific Aim #1) and that EAA receptors of
    both the N-methyl-D-aspartate (NMDA) and kainate sub-types are critically
    involved in the generation of the preovulatory LH surge (Specific Aim
    #2). Furthermore, the results are expected to demonstrate that at the
    time of puberty the LHRH neurons of the preoptic area primarily express
    EAA receptor of the NMDA sub-type while those of the arcuate nuclei
    primarily express EAA receptors of the kainate sub-type (Specific Aim
    #3). It is predicted that expression of these receptors in LHRH neurons
    first occurs during the peripubertal period and plays a pivotal role in
    triggering sexual maturation. The involvement of EAA receptors in
    regulating the pattern of LHRH secretion (Specific Aims #1 & 2) will be
    examined in vivo by administering various EAA agonists and antagonists
    and monitoring alterations in the pulsatile or surge patterns of LH
    and/or LHRH secretion. Elucidation of the neural circuits through which
    EAAs influence the activity of LHRH neurons (Specific Aims #3) will be
    investigated in vitro using combined immunocytochemistry and in situ
    hybridization to demonstrate co-localization of either NMDA or kainate
    receptor MRNAS within LHRH neurons. It is envisioned that the results
    will significantly further our understanding of the neuroendocrine
    control of puberty and reproductive function. In a broader context, they
    should also help to lay the foundation for the development of novel
    approaches to contraception and the treatment of human infertility.
    StatusFinished
    Effective start/end date9/1/933/31/08

    Funding

    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $250,425.00
    • National Institutes of Health: $244,540.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $250,425.00
    • National Institutes of Health: $250,425.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $250,425.00

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    Excitatory Amino Acids
    Gonadotropin-Releasing Hormone
    Reproduction
    Ionotropic Glutamate Receptors
    Glutamate Receptors
    Amino Acid Receptors
    Kainic Acid
    N-Methylaspartate
    Sexual Maturation
    Neurons
    Macaca mulatta
    Gene Expression
    Neurotransmitter Agents
    Puberty
    Steroids
    Infertility
    Pharmacology
    Central Nervous System
    alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
    Macaca

    ASJC

    • Medicine(all)