THE NEUROCHEMISTRY OF THE GNRH PULSE-GENERATOR

We review the crucial role of the two neurotransmitters norepinephrine (NE) and GABA in eliciting GnRH pulses. NE acts via an alpha 1-recept or mechanism and also GABA acts al the alpha-subtype of the GABA recep tor. The function of NE appears to be induction of phasic activation o f GnRH neurons and GABA inhibits GnRH neurons tonically until they are all ready for phasic activation. By an unknown mechanism preoptic GAB A release is dramatically reduced which causes simultaneous desinhibit ion of the GnRH neurons. Hence they release their product into the por tal vessels simultaneously which is the appropriate signal for the pit uitary ganodotrophs. The action of norepinephrine and GABA is most lik ely exerted at the perikarya level of the GnRH neurons since the al-ad reno receptor blocker doxazosin and GABA inhibit GnRH secretion only w hen applied into the medial preoptic/anterior hypothalamic area (where in the rat brain the GnRH perikarya are located). Utilizing a quantit ative reverse transcription polymerase chain reaction, we demonstrate furthermore that GnRH receptors are present in the mediobasal hypothal amus as well as in the preoptic area of rats: Their function appears t o serve autoinhibitory purposes since Buserelin added to medium signif icantly decreased GnRH release. Simultaneously, the release of GABA wa s increased and that of glutamate decreased. We conclude from these ex periments that GABAergic and glutamatergic neurons in the hypothalamus may also be GnRH-receptive.