Neurotoxic xenobiotics induce the alterations in neurotransmitter regulation of gonadoliberin circadian rhythms

Abstract

Objective. Experiments on chronic inhalation of various xenobiotics (toluene, dioxane, formaldehyde) dosed in both maximal permissible concentration and limited chronical range have been carried out on female rats to discover their effects on biogenic amines system in brain structures related to gonadoliberin (GnRH) synthesis and secretion.

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Methods. Dopamine, serotonine and their metabolites (3,4-dihydroxyphenylacetic acid and 5-hydroxy indole acetic acid respectively) content has been determined in preoptic area and medial eminence by HPLC with electrochemical detection.

Results and Conclusion. It has been shown that contents of GnRH and biogenic amines (dopamine and serotonine) that regulate its synthesis and secretion in medial eminence and especially in preoptic area of hypothalamus change in the opposite way in control rats. The low level of GnRH corresponds to a high content of biogenic amines in the morning, the opposite time course being revealed in the evening. Neurotoxic xenobiotics (toluene, dioxane) opposite to formaldehyde cause the disturbance of these normal circadian rhythms of GnRH secretion due to the decrease of dopamine and serotonine, as well as their metabolites, showing the inhibitory effect on the neurons in brain areas investigated.