Decreased TRH receptor mRNA activity precedes homologous downregulation: Assay in oocytes

Ligand-induced decrease in cell-surface receptor number (homologous downregulation) is often due to rapid receptor internalization. Thyrotropin-releasing hormone (TRH), however, causes a slow downregulation of TRH receptors (TRH-Rs), with a half-time of approximately 12 hours, in GH ₃ rat pituitary cells. The mechanism of TRH-R downregulation was studied by monitoring TRH-evoked depolarizing currents in Xenopus oocytes injected with GH₃ cell RNA as a bioassay for TRH-R messenger RNA (mRNA) activity. In GH₃ cells, TRH caused a rapid decrease in TRH-R mRNA activity to 15 percent of control within 3 hours. Because the half-life of TRH-R mRNA activity in control cells was approximately 3 hours, the rapid decrease in mRNA activity was not due to inhibition of mRNA synthesis alone and may represent a post-transcriptional effect.