REGULATION OF LUTEINIZING-HORMONE-RELEASING HORMONE AND LUTEINIZING HORMONES SECRETION BY HYPOTHALAMIC AMINO-ACIDS

1. The present review discusses the proposed roles of the amino acids glutamate and GABA in the central regulation of luteinizing hormone-re leasing hormone (LHRH)and in luteinizing hormone (LH) secretion. 2. De scriptions of the mechanisms of action of these neurotransmitters have focused on two diencephalic areas, namely, the preoptic-anterior hypo thalamic area where the cell bodies of LHRH neurons are located, and t he medial basal hypothalamus which contains the nerve endings of the L HRH system. Increasing endogenous GABA concentration by drugs, GABA ag onists, or blockade of glutamatergic neurotransmission by selective an tagonists in rats and non-human primates prevents ovulation and pulsat ile LH release, and blunts the LH surges induced by estrogen or an est rogen-progesterone combination. In contrast, glutamate and different g lutamate agonists such as NMDA, AMPA and kainate, can increase LHRH/LH secretion. 3. The simultaneous enhancement of glutamatergic activity and a decrease of GABAergic tone may positively influence the maturati on of the pituitary-gonadal system in rats and non-human primates. Adm inistration of glutamate receptor agonists has been shown to significa ntly advance the onset of puberty. Conversely, glutamate antagonists o r increased endogenous GABA levels may delay the onset of puberty. The physiological regulation of LHRH/LH secretion may thus involve a GABA -glutamate interaction and a cooperative action of the various types o f ionotropic glutamate receptors. 4. The inhibitory actions of GABA on LH release and ovulation may be exerted at the level of afferent nerv e terminals that regulate LHRH secretion. A likely candidate is noradr enaline, as suggested by the synaptic connections between noradrenergi c nerve terminals and GABAergic interneurons in the preoptic area. Rec ent experiments have provided complementary evidence for the physiolog ical balance between inhibitory and excitatory transmission resulting in modulation of the action of noradrenaline to evoke LHRH release.