Control of LH and FSH release by LHRH: Influence of putative neurotransmitters

gonadotropin secretion is controlled by LHRH, the secretion of which is modulated by the negetive and positive feedback actions of gonadal steroids. In addition to their CNS sites of action, gonadal steroids also act on the anterior pituitary, increasing or decreasing the sensitivity and responsiveness of the gland to LHRH. The neurohormone itself increase the responsiveness of the gonadotrophs to its own action. It appears that LHRH secretion and hence that of gonadotrophin is primarily controlled by monoaminergic transmitters, which are presumably released at synapses that impinge on the LHRH-secreting neurones. Strong evidence has been provided in favour of a stimulatory role of norepinephrine on gonadotrophin release. Dopamine appears either to facilitate or to inhibit the release of LHRH, according to the steroid millieu existent and possibly according to the degree of dopaminergic activation. Although recent pharmacological evidence suggest that DA may play a stimulatory role on LHRH secretion during the preovulatory surge of gonadotrophins, DA can also inhibit LH release in some other circumstances, thus reflecting the complexity of its actions on excitatory or inhibitory receptors. Another monoamine, serotonin, seems to exert a predominantly inhibitory role on LHRH secretion. Under certain circumstances, LHRH secretion can also be stimulated by acetylcholine and the central amino acid γ-aminobutyric acid (GABA). The role of histamine, another putative central neurotransmitter, in the control of LHRH secretion appears obscure at present. Regarding the mechanism of action of norepinephrine in facilitating LHRH release, it can be postulated that increased NE transmission activates the formation of prostaglandin E, which in turn stimulates the release of LHRH by acting within LHRH neurones located at both the median eminance-medial basal hypothalamus region and preoptic area. Whether PGE acts directly on the LHRH-releasing machinery or activates it through the formation of a cyclic nucleotide remains to be elucidated.