Role of melatonin in affecting disturbances of central regulation of reproduction by neurotoxicants

An effect of neurotropic xenobiotic 1,2-dymethylhydrazine (DMH) on hypothalamic regulation of female rat reproduction has been studied. A disturbance of diurnal rhythms of biogenic amines in brain areas responsible for gonadoliberin synthesis and secretion (preoptic area of the hypothalamus – PA, and median eminence – ME), and in suprachiasmatic nuclei of the hypothalamus as a main circadian rhythms pace-maker, has been found. DMH has been shown to be able to cause various changes in diurnal rhythms of the biogenic amines (dopamine, norepinephrine, serotonin) contents in these brain areas, and in reactive oxygen species (ROS) formation in PA, which can be due to diurnal variations in neurotransmitter levels in this area of the hypothalamus. Taking into account a role of melatonin produced in the pineal gland in circadian rhythms organization, an effect of exogenous melatonin on the above changes caused by DMH has been investigated. The gonadoliberin contents in PA and ME of rats undergone administration of DMH and melatonin have been studied. DMH has been shown not to cause sensible changes in the gonadoliberin contents in PA and ME, while melatonin itself and on the background of DMH administration significantly decreased gonadoliberin levels. Administration of DMH causes less significant changes in biogenic amines compared to melatonin. Also, melatonin in both absence and presence of DMH aggravates ROS formation in PA as well as in the whole hypothalamus. Our data allow supposition that exogenious melatonin is not capable of recovering processes of regulation of reproduction that were disturbed by neurotoxicant xenobiotics. Acknowledgements:  Supported by RBRF grant #00-04-48967.