A novel post-transcriptional mechanism of regulation of luteinizing hormone receptor expression by an RNA binding protein from the ovary

Luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor, a member of the rhodopsin/β₂ adrenergic receptor subfamily of G-protein coupled receptors, is expressed primarily in the gonads and essential for the regulation of reproductive function. In the ovary, the expression of the receptor is post-transcriptionally regulated under physiological conditions. Studies from our laboratory showed that the ligand-induced down-regulation of the receptor occurs by accelerated degradation of the mRNA rather than by decreased transcription. We have identified a cytoplasmic LHR mRNA binding protein (LRBP) as a trans-acting factor in regulating LHR mRNA levels. LRBP binds to the coding region of LHR mRNA and causes accelerated degradation of mRNA. The RNA binding activity of LRBP was found to be inversely correlated to LH/hCG receptor mRNA levels. LRBP was purified to homogeneity and its identity was established as mevalonate kinase by N-terminal microsequencing and MALDI analysis. Mevalonate kinase, an enzyme involved in de novo synthesis of cholesterol, belongs to the GHMP family of kinases having a potential RNA binding fold. The expression of MVK mRNA and MVK protein levels were induced in response to hCG treatment prior to the down-regulation of LH/hCG receptor mRNA expression. A model for the post-transcriptional regulation of LH/hCG receptor in the ovary by mevalonate kinase is proposed.