Involvement of serotonin in the regulation of GnRH gene expression in the male rat brain.

The role of serotonin (5-HT) in the regulation of the hypothalamo-pituitary-gonadal axis is still controversial. In order to evaluate the influence of 5-HT on gonadotropin-releasing hormone (GnRH) neurons, we have investigated the effects of repeated administration (during 2 days) of 5-HT, the 5-HT1+2 receptor antagonist methysergide, the 5-HT2 receptor antagonist ketanserin, and the 5-HT3 receptor antagonist ondansetron on GnRH mRNA levels in the male rat medial preoptic area (MPOA), as measured by quantitative in situ hybridization. The treatment with 5-HT decreased by 32% the number of silver grains overlying labelled neurons. The administration of methysergide and ketanserin increased the hybridization signal by 32% and 29%, respectively. On the other hand, the 5-HT3 receptor antagonist did not modify GnRH mRNA levels. The present results clearly indicate that the serotoninergic system exerts a negative tonic influence on the biosynthesis of GnRH as evaluated by mRNA level measurements. They also strongly suggest that the influence of 5-HT in the regulation of GnRH neuronal activity is mediated via activation of 5-HT2 receptor, although an involvement of 5-HT1 receptors cannot be totally excluded.