The distribution of 14C and 3H labeled thyrotropin-releasing hormone (TRH) has been studied in mice and rats. In the normal rat, 1-3 hours after the injection of 14C or 3H labeled TRH, the tissue to plasma ratio (T/P) exceeded 1 in the anterior pituitary, liver and kidney. This indicated that radioactivity accumulated in these organs. No accumulation of radioactivity was noted in the cerebral cortex or hypothalamus. Fifteen minutes to 2 hours after injection of 14C or 3H labeled TRH into mice, the T/P ratio showed an accumulation of radioactivity in the whole pituitary gland, liver and kidney but none in the hypothalamus or cerebral cortex. Tritiated proline and histidine, but not glutamic acid, also seem to accumulate in the pituitary. However, administration of a large dose of pyroglutamic acid, histidine and proline, together with the 14C TRH, does not decrease the accumulation of the radioactivity in the pituitary. Extraction followed by chromatography and electrophoresis of the radioactivity found in the anterior pituitaries of rats given 14C-TRH, indicates that the major constituents are TRH, glu-his-pro-OH and the free acid of TRH. These data together with the information that TRH is inactivated by plasma in vitro by deamidation, and not a breakdown to individual amino acids, suggest that radioactive TRH may be accumulated in the pituitary.
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