Development of the gonadotropin-releasing hormone (GnRH) neuronal system in the mouse.
Item
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Title
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Development of the gonadotropin-releasing hormone (GnRH) neuronal system in the mouse.
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Identifier
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AAI9304695
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identifier
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9304695
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Creator
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Livne, Izhar.
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Contributor
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Adviser: Marie J. Gibson
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Date
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1992
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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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Biology, Cell | Biology, Neuroscience
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Abstract
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I have analyzed the cellular associations of GnRH cells during their migration and how their migration is correlated with their biochemical and morphological differentiation. Ultrastructural observations revealed that these neurons migrate through the nasal septum within axonal fascicles of the olfactory and vomeronasal nerves. These axonal fascicles subserve as a conduit through which GnRH neurons migrate into the forebrain. This study also revealed that the capability to process GnRH to its bioactive form is acquired during the transition from the nasal septum to the forebrain.;During their migration in the nasal septum many GnRH neurons express the growth associated protein GAP-43 which is associated with axonal growth. However, once in the forebrain, most GnRH neurons cease to express GAP-43 and, unlike other neuronal populations, GnRH axons do not accumulate GAP-43 as they extend towards their target.;I tested whether interrupting the migration of GnRH neurons would interfere with their capability to complete their maturation. For these experiments I used the mutant hypogonadal (hpg) mouse which has an undeveloped reproductive tract due to a truncated GnRH gene. I transplanted normal fetal nasal septum tissue, containing the migratory population of GnRH neurons, into the brain of adult hpg. Some of the transplanted neurons continued their migration in the host brain and their axons grew through the host parenchyma to terminate at their normal target where they secreted bioactive GnRH. Thus, heterochronic transplantation of migratory GnRH neurons does not prevent them from completing their differentiation and establishing their functional connections.;The truncated GnRH gene is transcribed in the hpg brain but the neuropeptide is not synthesized. Using in situ hybridization and retrograde tracing I established that the mutant neurons, that are devoid of their major neurosecretory product can, nevertheless, elaborate their axonal projections to their primary secretory target. I concluded that the capability of GnRH neurons to recognize and interact with their target is independent of their neurosecretory function.;Finally, I have demonstrated that testosterone administration to neonatal hpg males can restore their reproductive capability. This finding indicates that GnRH secretion is already functional and critical for stimulation of the pituitary-gonadal axis in the early postnatal period.
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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.
