REGION-SPECIFIC EXPRESSION OF THYROTROPIN-RELEASING HORMONE-DEGRADINGECTOENZYME IN THE RAT CENTRAL-NERVOUS-SYSTEM AND PITUITARY-GLAND

Thyrotrophin-releasing hormone (TRH), a hypothalamic neuropeptide horm one and a putative neuromodulator/neurotransmitter in the central nerv ous system is inactivated by the TRH-degrading ectoenzyme (TRH-DE), a TRH-specific metallopeptidase localized on the surface of neuronal bra in cells in culture and on lactotrophic cells of the pituitary. After succeeding in cloning the cDNA of TRH-DE we now report on the cellular distribution pattern of this enzyme in rat brain, spinal cord and pit uitary gland using in situ hybridization histochemistry. In the pituit ary, TRH-DE mRNA was found both in the anterior and the neural lobe bu t not in the intermediate lobe. After treatment with triiodothyronine (T-3) a dramatic increase in the mRNA levels of the TRH-DE and a decre ase in the intensity of the TRH receptor could be observed in the ante rior lobe of the pituitary. In brain, TRH-DE transcripts were predomin antly found in neo-and allocortical regions with strongest signals in the olfactory bulb, the piriform cortex, the cerebral cortex, the gran ular layer of the cerebellar cortex and the pyramidal cells of the Amm on's horn. In the diencephalon, the highest TRH-DE mRNA levels were ob served in the medial habenulae followed by several hypothalamic subreg ions. In the mesencephalon and brainstem, moderate signals were presen t in the superior colliculi, substantia nigra, dorsal raphe and in the periolivar region. In the spinal cord, TRH-DE mRNA positive neurons w ere present in all layers. The very distinct distribution of TRH-DE in the brain and the hormonal regulation of the adenohypophyseal enzyme support the concept that this peptidase serves very specialized functi ons.