[Molecular cloning and posttranslational processing of human preprothyrotropin-releasing hormone]

Human PreproTRH gene and its hypothalamic cDNA were cloned. The human preproTRH protein contains six copies of TRH progenitor sequence flanked by paired basic amino acids. Radioimmunoassays with specific antibodies raised against five human preproTRH cryptic peptides and chromatographic analyses identified that the posttranslational processing of preproTRH in hypothalami and placentae could be different. Moreover, transfection assays using human preproTRH promoter-luciferase chimeric-plasmids demonstrated that human preproTRH promoter activities were regulated negatively by T3 in GH3 cells. Cloning of the human preproTRH gene would facilitate the elucidation of the molecular mechanism of actions of TRH and TRH cryptic peptides in human hypothalamo-pituitary-thyroid axis and central nervous system.