Thyrotropin-releasing Hormone in the Systemic Circulation of the Neonatal Rat Is Derived from the Pancreas and Other Extraneural Tissues

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Abstract
Thyrotropin-releasing hormone immunoreactivity (IR-TRH) has been detected in the circulation of the neonatal rat. This immunoreactivity was demonstrated in purified ethanol extracts of plasma, and was indistinguishable from synthetic TRH using radioimmunoassay and chromatographic criteria. To determine the source of the circulating IR-TRH, tissue concentrations of TRH were analyzed during maturation of the rat. These studies revealed that during the first 10 d of life, the pancreas contained the greatest concentration of IR-TRH of any organ (pancreas, 289±35 pg/mg; hypothalamus, 13±3 pg/mg, day 5). Thereafter, pancreatic IR-TRH concentrations declined progressively while hypothalamic concentrations gradually increased (pancreas, 1.2±0.2 pg/mg; hypothalamus, 365±54 pg/mg, adult rat). IR-TRH was also found throughout the gastrointestinal tract but was not detected in the liver, spleen, kidney, or heart. IR-TRH from the pancreas and gastrointestinal tract gave radio-immunoassay binding displacement curves that were parallel to a curve generated with synthetic TRH, and co-migrated with synthetic TRH on Sephadex G-10 and high performance liquid chromatography. In addition, IR-TRH from purified pancreatic extracts was biologically active in that it released thyrotropin and prolactin from rat adenohypophysial cells maintained in monolayer culture. When a total pancreatectomy was performed on the 5th d of life of the rat, mean plasma TRH concentrations were significantly decreased 3 h afterwards (84±9 vs. 63±7 pg/ml, P < 0.05). Neither the TRH concentrations in the brain, hypothalamus, or gastrointestinal tract, nor the pituitary-thyroid axis were affected by the pancreatectomy. However, mean plasma TRH concentrations remained unaltered 3 h after removal of the hypothalamus and extrahypothalamic brain. From these results we conclude the following: (a) the TRH immunoreactivity in the circulation, pancreas, and gastrointestinal tract of the neonatal rat is indistinguishable from synthetic TRH; (b) pancreatic secretion provides a significant contribution to the IR-TRH in plasma, and a proportion of the circulating IR-TRH is derived from other extraneural sites. These findings therefore imply that alterations in hypothalamic and extrahypothalamic brain secretion of TRH are not reflected by changes in levels of this tripeptide in the systemic circulation.