Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice.
Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic-pituitary-gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.
['Rijal|Santosh|S|0000-0002-1924-4457', 'Cho|Dong Hyu|DH|', 'Park|Seon-Ah|SA|0000-0001-9782-5399', 'Jang|Seon Hui|SH|', 'Ábrahám|István M|IM|', 'Han|Seong Kyu|SK|']
D000818:Animals D001921:Brain D018690:Excitatory Amino Acid Agonists D005260:Female D007987:Gonadotropin-Releasing Hormone D049452:Green Fluorescent Proteins D007608:Kainic Acid D008297:Male D008550:Melatonin D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D016202:N-Methylaspartate D009474:Neurons D037342:Pertussis Toxin D011627:Puberty D018092:Receptors, Kainic Acid D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
melatonin kainate gonadotropin-releasing hormone neuron patch clamp G-protein-coupled receptors