The luteinizing hormone receptor (LHR) is essential for elevated levels of progesterone to maintain pregnancy during the first trimester; the maintenance of the expression of LHR is a key factor controlling the duration of luteal function. Therefore, as the expression of LHR is most likely to be regulated by the stability of the receptor mRNA at the luteal phase of the human menstrual cycle, we focused on studies examining the stability of mRNA rather than the production of mRNA. In addition, LHR (exon 9), one of the splice variants of human LHR (hLHR), was cloned in the corpus luteum of a patient with a regular menstrual cycle. The results of Western blots using Percoll gradient fractionation indicated that hLHR formed complexes with hLHR (exon 9), which are transferred to the lysosome, where they are eventually degraded, instead of being translocated from the endoplasmic reticulum to the transducing organelle. These results showed that hLHR (exon 9) caused a reduction in the expression of functional receptor number and affected the signaling condition of wild-type hLHR. As the luteal phase progressed hLHR (exon 9) increased relative to hLHR, demonstrating that hLHR (exon 9) was expressed more than hLHR in the late luteal phase. This work reveals the essential function of the regulatory and structural elements involved in human LH receptor splicing, and that hLHR (exon 9) can negatively control the function of wild-type receptors. Moreover, this finding presented a novel mechanism of regulation of LHR in the human corpus luteum. (Reprod Med Biol 2008; 7: 11-16).
Keywords: E2; human luteinizing hormone receptor; ovary; splicing of human LHR.