Noradrenergic neurotoxin suppresses gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in ovariectomized and steroid-treated rats

The present study was designed to investigate whether noradrenergic neurotr ansmission regulates the gene expression of gonadotropin-releasing hormone (GnRH) in the preoptic area and GnRH receptor in the pituitary, To this end , N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4, 50 mg/kg), an intrape ritoneal (i.p.) injection of selective noradrenergic neurotoxin, was admini stered 1 h before progesterone (1 mg) treatment in ovariectomized and estra diol-treated prepubertal rats. Treatment with DSP4 effectively blocked the progesterone-induced increase in hypothalamic noradrenaline content, but no t dopamine content, indicating that DSP4 selectively inhibits noradrenergic neurotransmission, DSP4 significantly blocked progesterone-induced increas e in serum luteinizing hormone (LH) concentrations as well as GnRH release from hypothalamic fragments incubated in vitro. DSP4 concomitantly down-reg ulated GnRH mRNA levels in the preoptic area, as determined by competitive reverse transcription-polymerase chain reaction. DSP4 also clearly down-reg ulated progesterone-induced GnRH receptor mRNA levels in the pituitary, whe reas it failed to alter LH beta mRNA levels. In summary, blockade of noradr energic neurotransmission with DSP4 resulted in profound reductions of hypo thalamic GnRH and pituitary GnRH receptor gene expression.