Neuromodulation of luteinizing hormone secretion in the mouse.
Item
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Title
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Neuromodulation of luteinizing hormone secretion in the mouse.
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Identifier
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AAI9405559
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identifier
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9405559
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Creator
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Miller, Gregory Michael.
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Contributor
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Adviser: Marie J. Gibson
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Date
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1993
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Language
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English
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Publisher
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City University of New York.
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Subject
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Engineering, Biomedical | Biology, Neuroscience | Health Sciences, Pharmacology
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Abstract
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The endogenous opioid system and the excitatory amino acids are important modulators of Luteinizing Hormone (LH) secretion. In many species, the opiate antagonist Naloxone (NAL) stimulates LH release. However, NAL fails to do so in mice. The excitatory amino acid analog, N-methyl-D,L-aspartic acid (NMA), stimulates LH secretion via an excitatory action on Gonadotropin-releasing Hormone (GnRH) neurons. Endogenous opioid interactions with NMA were studies in both normal male mice and in hypogonadal (HPG) mice with fetal preoptic area (POA) brain grafts (HPG/POA). These grafts contain GnRH neurons which integrate with the host brain and stimulate reproductive development in these GnRH-deficient mice. NAL and its quaternary derivative NAL methiodide (NALMI) failed to elicit LH release in any mice tested. Either opiate antagonist significantly potentiated NMA-stimulated LH release in young adult normal male mice but not older normal male mice. However, the older male mice had significantly larger LH responses to NMA than younger male mice. GnRH challenges were unaffected by NAL pretreatment, suggesting that the action of the opiate antagonists on LH release is at a suprapituitary location outside of the blood-brain barrier. A similar significant action of opiate antagonists was found in female HPG/POA. {dollar}\beta{dollar}-endorphin immunocytochemistry on the brains of female HPG/POA revealed that immunoreactive fibers of host origin innervate the graft, suggesting that {dollar}\beta{dollar}-endorphin neurons are an anatomical substrate for the opiate-antagonist-induced potentiation of the NMA-stimulated LH response. Only a few old male HPG/POA with long-term functioning grafts were able to respond to NMA, and these responses were not opiate-antagonist sensitive. To determine whether steroid milieu modulates NMA-stimulated LH release, intact, castrated and castrated + 17-{dollar}\beta{dollar}-Estradiol (E2)-treated male HPG/POA were challenged repeatedly with NMA. Only E2 treated male HPG/POA responded to NMA, suggesting that NMA-stimulated LH release is mediated by estrogen-sensitive afferents to GnRH neurons. A final study demonstrated that intrahypothalamic implants of an immortalized GnRH-secreting cell line (GT1) can support NMA-stimulated LH release in female HPG/POA.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
