Post-transcriptional mechanism plays a crucial role in regulating luteinizing hormone receptor (LHR) expression in the ovary. We have identified a novel trans-factor, LRBP, which binds to a polypyrimidine rich bipartite sequence of the coding region of LHR mRNA and its identity was established as mevalonate kinase (Mvk). Although an inverse relation between LHR mRNA expression and RNA binding activity of LRBP has been established, its intermediary role in LHR mRNA expression has not been demonstrated. The present study examined the direct role of Mvk in regulating LHR expression by using primary cultures of human granulosa cells as a model system. A marked decrease in LHR mRNA stability and an increase in Mvk expression were seen when cultured granulosa cells were treated with human chorionic gonadotropin (hCG) in vitro. This treatment also resulted in an increase in LHR mRNA binding activity in the cytosolic fractions prepared from hCG treated cells compared to the control. Since Mvk expression is regulated by sterol response element binding protein-1 (SREBP-1) which is sensitive to the cellular concentration of 25-hydroxycholesterol (25-OHC), cultured granulosa cells were treated with this oxysterol and the expression of Mvk gene was examined. As expected, treatment with 25-OHC inhibited the Mvk (LRBP) expression, as well as the LHR mRNA binding activity of LRBP. To determine the role of Mvk in ligand-mediated down regulation of LHR mRNA, cells were additionally treated with 25-hydroxycholesterol when treated with hCG. The results showed that the decrease in Mvk expression by oxysterol treatment abrogated ligand-induced down regulation of LHR mRNA. These results therefore establish a direct participation of Mvk in regulating LHR expression and suggest a novel relationship between cholesterol metabolism and LHR expression in the ovary.