Thyrotropin-Releasing Hormone (TRH): Distribution in Hypothalamic and Extrahypothalamic Brain Tissues of Mammalian and Submammalian Chordates

Abstract

A sensitive and specific radioimmunoassay for TRH is reported. Antibody was raised in a New Zealand white rabbit by immunization with TRH complexed to bovine thyroglobulin through bis-diazotized benzidine. The assay was capable of detecting below 7 pg of TRH in biological materials. Immunoreactive TRH was found in hypothalamic extracts from man, pig, rat, hamster, chicken, frog, snake, salmon, and in whole brain of the larval form of the primitive cyclostome lamprey, and in the head region of the protochordate amphioxus. The TRH levels in the frog hypothalamus were 1520–3620 pg/mg tissue, being 6–12 times the concentration detected in the rat hypothalamus. These findings indicate that TRH is distributed throughout the vertebrate kingdom, and has an ancient lineage. Immunoreactive (IR) TRH up to 764 pg/mg tissue was found in brain regions, other than hypothalamus, of the lower vertebrates, snake, frog, tadpole and salmon. Small but significant concentrations were also found in extrahypothalamic brain of the chicken and rat, the olfactory lobes containing mean levels of 17 and 6 pg/mg tissue, respectively. In all these species the highest brain concentrations occur in the hypothalamus and/or pituitary complex, though quantitatively in the lower species much more TRH lies outside that area; even in the rat, the total quantity outside the hypothalamus is close to that found in the whole hypothalamus itself. The identity of the IR-TRH measured was shown by the ability of extrahypothalamic frog brain extracts to release TSH from the rat pituitary in vivo. These findings suggest an extrathyroidal brain function for this tripeptide, possibly as a central neurotransmitter. (Endocrinology95: 854, 1974)