A novel method to modulate desensitization and truncation of luteinizing hormone receptors using antisense oligodeoxynucleotides.
We report a novel method to study the mechanisms of luteinizing hormone (LH) receptor desensitization and truncation, using antisense oligodeoxynucleotides that code for regions of the NH2-terminus, the third extracellular loop and the C-terminus of the LH receptor. Mouse tumour (MA10) Leydig cells were incubated for 48 h with the addition of 2.5 microM antisense oligodeoxynucleotides at time 0 and 24 h. It was found that the NH2-terminus oligodeoxynucleotide completely inhibited synthesis of the LH receptor. Pretreatment with the third extracellular loop oligodeoxynucleotide inhibited LH-, dibutyrylcyclic AMP (db-cAMP)- and phorbol 12-myristate 13-acetate (PMA)-induced desensitization and truncation of LH receptors. Truncation but not desensitization, of the LH receptor was prevented in cells pretreated with the C-terminus oligodeoxynucleotide. These results indicate that different sites of the C-terminal intracellular tail of the LH receptor are involved in the regulation of desensitization and truncation of the LH receptor.
West
A P
AP
Department of Biochemistry, Royal Free Hospital School of Medicine, London, U.K.
Cooke
B A
BA
D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007984:Leydig Cell Tumor / Q000503:physiopathology; D007986:Luteinizing Hormone / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011284:Pregnenolone / Q000378:metabolism; D011974:Receptors, LH / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D011974:Receptors, LH; D003994:Bucladesine; D011284:Pregnenolone; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate