The effect of splice variant of the human luteinizing hormone (LH) receptor on the expression of gonadotropin receptor.

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 regular 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. Interactions between hLHR (exon 9) with the immature bands of gonadotropin receptors not with the mature bands were seen. This phenomenon is specific among gonadotropin receptors since human thyrotropin-receptor (hTSHR) failed to be coimmunoprecipitated. Furthermore, this receptor complex attenuated the receptor protein level within the cells. To elucidate the mechanism underlying the decrease in receptor protein by this receptor complex, we performed a Percoll-fractionation experiment, which indicated the receptor complex drove hLHR to the lysosome instead of the plasma-membrane. Moreover, the expression of hLHR (exon 9) mRNA was seen at all phases of the menstrual cycle and relatively increased as the luteal phase progressed. These results reveal a novel mechanism of regulation for gonadotropin receptor expression.