A splice variant of human lutropin/choriogonadotropin-receptor [hLHR(exon 9)] that lacks exon 9 was previously cloned in the corpus luteum of a woman with a normal menstrual-cycle. Supported by detergent soluble binding assay and receptor biotinylation experiment, the receptor binding assay shows hLHR(exon 9) is neither expressed at the cell surface nor have the capability of binding to hCG. In addition, hLHR(exon 9) was confirmed in the endoplasmic-reticulum (ER) by Endoglycosidase-H treatment. A co-immunoprecipitation experiment clearly showed that hLHR(exon 9) and constitutively inactivate mutant-LHRs, which stay in the ER, form an association with the human follitropin-receptor (hFSHR). This suggests that in the presence of mutant-LHR, hFSHR which is trapped in the ER and associated with hLHR(exon 9) is unable to come up to the plasma-membrane. This phenomenon is specific among gonadotropin-receptors since human thyrotropin-receptor (hTSHR) failed to be co-immunoprecipitated. Furthermore, this receptor complex attenuated the hFSHR receptor protein level within the cells, which impaired cAMP production. To elucidate the mechanism underlying the decrease in hFSHR protein by this receptor complex, we performed a Percoll-fractionation experiment, which indicated the receptor complex drove hFSHR to the lysosome instead of the plasma-membrane. These results reveal a novel mechanism of FSHR expression regulation.