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Title: Regulation of gonadotropin-releasing hormone neurons by the neurotransmitter glutamate
Author: Ford, H.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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The neurotransmitter glutamate has been proposed as a potential regulator of the onset of puberty, due to its actions on the neurons within the hypothalamus which release gonadotropin-releasing hormone (GnRH). The studies in this thesis have investigated this hypothesis, by determining the effects of glutamate on GnRH gene expression and the effects of manipulating the ability of glutamate to signal to the GnRH neurons via N-methyl-D-aspartate (NMDA)-type glutamate receptors. Studies in this thesis utilised two transgenic mouse lines with mutations in the common NR1 subunit of the NMDA receptor. One line was to complete knockout for this gene (NRI-/-), and the other contained a point mutation which rendered it dysfunctional (NRIQ/Q). Both lines were shown to possess a normal number of GnRH perikarya, in a normal distribution. The approach of semi-quantitative in situ hybridisation was used to demonstrate that GnRH mRNA levels increased with developmental age in the mouse. The neurotransmitter glutamate was shown to be involved in the endogenous regulation of GnRH mRNA levels in the mouse, and is proposed as a potential regulator of the developmental increase. Glutamatergic stimulation had no effect on GnRH mRNA within NRI-/- animals, showing that these effects are likely to be mediated by NMDA receptors. The functional capability of the GnRH neurons of NRIQ/Q animals was tested by transplanting them into the brain of the infertile, GnRH-deficient, hypogonadal (hpg) mouse. Grafted GnRH neurons from wild-type and NRIQ/Q animals were found to innervate the median eminence normally, and were capable of inducing increased testis size, increased serum testosterone and the onset of spermatogenesis in hpg male hosts.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available