Previous studies have shown that human CG (hCG) can down-regulate the expression of GnRH gene in GT1-7 neurons and that these neurons contain GnRH receptors and a self-stimulatory mechanism in the synthesis and release of GnRH. These findings have led us to hypothesize that hCG may down-regulate GnRH receptors to disrupt the self-stimulatory mechanism. To test this hypothesis, we cultured GT1-7 neurons in the presence or absence of an optimal concentration of highly purified hCG (100 ng/ml) and then measured steady-state levels of GnRH receptor messenger RNA (mRNA) transcripts and protein. Northern blotting demonstrated that GT1-7 neurons contain a major 5.5-kb and minor 2.4-kb and 1.6-kb GnRH receptor mRNA transcripts. Ligand blotting showed that GT1-7 neurons also contain 53-kDa and 43-kDa GnRH receptor proteins. Culturing with hCG resulted in a significant decrease in steady-state levels of GnRH receptor mRNA transcripts by 12 h and GnRH receptor proteins by 6 and 12 h, followed by a return to the controls by 24 h. The treatment with hCG had no obvious effect on the transcription rate of GnRH receptor gene. The hCG treatment, however, significantly decreased the half-life of GnRH receptor mRNA transcripts from 27 h to 16 h. In summary, we conclude that treatment with hCG can down-regulate the expression of GnRH receptor gene by decreasing the stability of transcripts in GT1-7 neurons. By down-regulating GnRH receptors, hCG may disrupt the self-stimulatory mechanism in GnRH synthesis.