Enzymic formation of TRH-OH from TRH by rat hypothalamus.

Specific radioimmunoassays for thyrotrophin-releasing hormone (TRH) and deamido-TRH (TRH-OH) were used to investigate the inactivation of TRH by subcellular fractions from rat hypothalamus. TRH-OH was rapidly formed from TRH by an amidase present only in the supernatant fraction at an optimum pH of 7.38; although TRH was degraded by the particulate fraction, no TRH-OH formation was detected. Of several brain areas investigated, the cortex had the highest rate of TRH-OH production and the pituitary the lowest. Once formed in the supernatant fractions, it was found that TRH-OH was stable and did not undergo further degradation. Formation of TRH-OH from TRH appears to be an important step in the tripeptide's enzymic degradation in the brain, so the combined use of specific radioimmunoassays for TRH and TRH-OH may provide a suitable means for studies of the enzymes involved, since these enzymes may contribute to the mechanisms regulating the secretion and duration of action of TRH.