Thyrotropin-releasing hormone (TRH), a signal peptide of the central nervous system

Thyrotropin-Releasing Hormone (TRH; pyroGlu-His-Pro-NH2), originally isolated as a hypothalamic neuropeptide hormone, most likely acts also as a neuromodulator and/or neurotransmitter in the central nervous system (CNS). This interpretation is supported by the identification of a peptidase localized on the surface of neuronal cells which has been termed TRH-degrading ectoenzyme (TRH-DE) since it selectively inactivates TRH. Vice versa it also holds true that TRH is selectively inactivated only by TRH-DE and thus, this enzyme might be considered to be the terminator of TRH signals. In situ-hybridization histochemistry was used to study the TRHergic communication system by analyzing the gene expression of TRH-DE in relation to TRH and to the TRH receptors (TRH-R1 and TRH-R2). TRH mRNA is highly expressed in "thyrotropic" hypothalamic regions and in some selected brain areas. For TRH-R1 and TRH-R2, an almost exclusive mRNA distribution pattern was noticed in many brain regions. Interestingly, a widespread distribution of TRH-DE predominantly in neo- and allocortical regions was observed essentially overlapping the distribution patterns of TRH-R1 and TRH-R2. These data support the hypothesis that TRH-DE is important in the TRH-mediated modulation of sensory, locomotor and cognitive functions of the CNS and could be considered to be a marker to map TRHergic pathways.