title: Luteinizing hormone receptor mRNA down-regulation is mediated through ERK-dependent induction of RNA binding protein.
abstract: The ligand-induced down-regulation of LH receptor (LHR) expression in the ovaries, at least in part, is regulated by a posttranscriptional process mediated by a specific LH receptor mRNA binding protein (LRBP). The LH-mediated signaling pathways involved in this process were examined in primary cultures of human granulosa cells. Treatment with 10 IU human chorionic gonadotropin (hCG) for 12 h resulted in the down-regulation of LHR mRNA expression while producing an increase in LHR mRNA binding to LRBP as well as a 2-fold increase in LRBP levels. The activation of ERK1/2 pathway in LH-mediated LHR mRNA down-regulation was also established by demonstrating the translocation of ERK1/2 from the cytosol to the nucleus using confocal microcopy. Inhibition of protein kinase A using H-89 or ERK1/2 by U0126 abolished the LH-induced LHR mRNA down-regulation. These treatments also abrogated both the increases in LRBP levels as well as the LHR mRNA binding activity. The abolishment of the hCG-induced increase in LRBP levels and LHR mRNA binding activity was further confirmed by transfecting granulosa cells with ERK1/2 specific small interfering RNA. This treatment also reversed the hCG-induced down-regulation of LHR mRNA. These data show that LH-regulated ERK1/2 signaling is required for the LRBP-mediated down-regulation of LHR mRNA.
authors.affiliation: Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0617, USA. kmjmenon@umich.edu
authors.forename: Bindu
authors.initials: B
authors.lastname: Menon
authors.forename: Megan
authors.initials: M
authors.lastname: Franzo-Romain
authors.forename: Shadi
authors.initials: S
authors.lastname: Damanpour
authors.forename: K M J
authors.initials: KM
authors.lastname: Menon
mesh_terms: D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D018613:Microscopy, Confocal; D009570:Nitriles / Q000494:pharmacology; D010053:Ovary; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002070:Butadienes; D006063:Chorionic Gonadotropin; D007546:Isoquinolines; D009570:Nitriles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011974:Receptors, LH; D013449:Sulfonamides; C113580:U 0126; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide