Distribution of Thyrotropin-Releasing Hormone (TRH) and Precursor Pep tide (TRH-Gly) in Adult Rat Tissues

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Abstract
TRH (pGlu-His-Pro-NH2) arises from the postranslational processing of a larger precursor peptide containing multiple copies of the TRH progenitor sequence, Gln-His-Pro-Gly. Concentrations of TRH and its precursor peptide (TRH-Gly) were determined in serum and a variety of tissues of the rat using specific RIA systems. TRH and TRH-Gly immunoreactivities were detectable in almost all tissues studied. TRH was distributed mainly in neural tissues, with the highest mean concentration (126 pg/mg tissue) in hypothalamus. In extraneural tissues, mean TRH levels ranged from 0.6-4.8 pg/mg tissue; the mean serum concentration was 12.4 pg/ml. In contrast to the distribution of RTH, relatively higher mean TRH-Gly concentrations were observed in serum (76.5 pg/ml) and in extraneural tissues, including prostate (83.3 pg/mg tissue), spleen (19.0 pg/mg), adrenal (16.2 pg/mg), kidney (13.3 pg/mg), and gastrointestinal tract (6.3-19.8 pg/mg). Among brain tissues, the TRH-Gly concentration was highest in pituitary gland (13.1 pg/mg). The mean ratio of TRH-Gly/TRH concentration was less than 1 in neural tissues and pancreas. The lowest ratio (0.04) was observed in hypothalamus, and the highest ratio (66) i nprostate gland. Assuming that tissue TRH-Gly levels reflect TRH synthesis, these results suggest that 1) the processing of TRH-Gly to TRH varies among tissues, 2) TRH-Gly to TRH conversion occurs most efficiently in neural tissues, and 3) THR-Gly to THR coversion may be a rate-limiting step in TRH biosynthesis.