It is well documented that central catecholamines(CA) can regulate the synthesis and secretion of gonadotrophin releasing hormone (GnRH) in the hypothalamus. However, to our knowledge, no attempt has been yet made to determine whether neural CA input would affect gene expression of GnRH. To this end, we examined the effect of 6-hydroxydopamine (6-OHDA), a CA depleting neurotoxin, on GnRH mRNA level. Hypothalamic tissues obtained from adult male rats were incubated in vitro with 6-OHDA containing medium for 2.5hr. Initially, to ensure the CA depleting action of 6-OHDA, CA levels in hypothalamic tissues were measured by a high performance liquid chromatography-coupled to electrochemical detector (HPLC-ECD). Increasing concentrations of 6-OHDA resulted in depletion of norepinephrine(NE) and dopamine(DA) contents in a dose dependant manner. To determine possible changes in GnRH mRNA by 6-OHDA treatment in vitro, postincubated hypothalamic tissues were recovered, and subjected to the isolation of poly(A) RNA fractions. Poly(A) RNA fractions were blotted onto nitrocellulose paper, and hybridized with p^(32)-end labeled synthetic GnRH oligonucleotide (29mer). RNA-blot hybridization showed that 6-OHDA (5×10^(-4)M) clearly reduced GnRH mRNA level by half over that in the control group. Interestingly enough, immunoreactive GnRH content in hypothalamic tissue was not modified by 6-OHDA, and GnRH release in the medium was rather elevated by 30% over that in the control group, suggesting that there is some difference in biosynthesis and secretion of GnRH molecules. In summary, these data demonstrated that GnRH gene expression is influenced by neural CA traffic, indicating transsynaptic regulation of GnRH gene expression.