The neurochemistry of the GnRH pulse generator
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We review the crucial role of the two neurotransmitters norepinerine (NE) and GABA in eliciting GnRH pulses.NE acts via an alpha1-receptor mechanism and also GABA acts at the alpha-subtype of the GABA receptor.The function of NE appears to be induction of phasic activation of GnRH neurons and GABA inhibits GNRH neurons tonically until they are all ready for phasic activation.By an unknown mechanism preoptic GABA release is dramatically reduced which causes simultaneous desinhibition of the GnRH neurons.Hence they release their product into the portal vessels simultanously which is the appopriate signal for the pituitery ganodotrophs.THe action of norepinerphine and GABA is most likely exerted at the perikarya level of the GnRH neurons since the alpha-1-adreno receptor blocker doxazosin and GABA inhibit GnRH secretion only when applied into the medial preoptic/anterior hypothalmic area.Utilizing a quantitative reverse transcription polymerase chain reaction, we demonstrate furthermore that GnRH receptors are present in the mediobasal hypothalmus as well as in the preoptic area of rats.Their function appears to serve autoinhibitory puroses since Buserelin addet to medium significantly decreased GnRH release.Simultanoeusly, the release of GABA was increased and that of glutamate decreased.We conclude from these experiments that GABAergic and glutamatergic neurons in the hypothalmus may also be GnRH-receptive.
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