Biosynthesis of proTRH-derived peptides in prohormone convertase 1 and 2 knockout mice

► This is the first study where the fate of proTRH biosynthesis and processing is analyzed in PC1KO and PC2KO mice. ► The current in vivo study confirms our initial in vitro and ex vivo findings demonstrating that PC1 plays a primary role in proTRH processing. ► PC1 is necessary to maintain normal levels of the biologically active thyroid hormone T3. ► PC2 is required for the conversion of the proTRH-derived peptide pFE22 to pFQ7, and pSE14, which may function to regulate prolactin.