A NOVEL METHOD TO MODULATE DESENSITIZATION AND TRUNCATION OF LUTEINIZING-HORMONE RECEPTORS USING ANTISENSE OLIGODEOXYNUCLEOTIDES

[摘要] 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-mu-M 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.

[发布日期] 1991-08-01

[关键词] ANTISENSE;OLIGODEOXYNUCLEOTIDE;RECEPTOR;DESENSITIZATION;LUTEINIZING HORMONE;LEYDIG CELL