TRH-Degrading Aminopeptidase

Abstract

TRH (Thyrotropin Releasing Hormone) was isolated as the first hypothalamic hypophysiotropic hormone and identified as the tripeptideamide pyroGlu-His-ProNH2. As a neuropeptide hormone TRH not only stimulates the secretion of thyrotropin, but also the secretion of prolactin. In brain, TRH content is not confined to the neuroendocrine nuclei of the hypothalamus but widely distributed throughout the central nervous system where it is considered to act as a neuromodulator and/or neurotransmitter. The inactivation of the signal peptide TRH is selectively catalyzed by one enzyme, the TRH-degrading aminopeptidase, also known as TRH-degrading ectoenzyme. Moreover, and most interestingly, this enzyme (unlike other neuropeptide-inactivating peptidases) exhibits an extraordinary high degree of substrate specificity and selectively inactivates only TRH. This dual selectivity provides a unique constellation for further studies in neuropeptide research. At the pituitary level the inactivation of the neuropeptide hormone TRH by the TRH-degrading aminopeptidase is strongly influenced by the hormonal conditions of the organism, indicating that the adenohypophyseal enzyme may serve regulatory functions for the balanced release of pituitary hormones. For the inactivation of the neuromodulator TRH in brain, the high enzymatic activities and the distinct mRNA distribution indicate that this enzyme may act as a terminator of TRH action, whereby the predominant concentration of the mRNA in neocortical brain areas suggests a role of the enzyme in the modulation of cognitive and higher integrative brain functions.