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

Abstract

A B S T R A C T Thyrotropin-releasing hormone immunoreactivity (IR-TRH) has been detected in the circulation ofthe 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 oflife, 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 radioimmunoassay 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 al 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.This work was presented in part at the 62nd Annual Meeting of the Endocrine Society, Washington, D. C., 18-20 June 1980.Received for publication 21 July 1980 and in revised form 30 October 1980. 800 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.

Thyrotropin-releasing Hormone in the Pancreas and Brain of the Rat Is Regulated by Central Noradrenergic and Dopaminergic Pathways

“…The experiments have been performed with animals of up to 21 d of age because at this time of life, marked ontogenetic changes in the TRH concentrations of the brain and pancreas are occurring (16)(17)(18)(19). It was therefore anticipated that in these developing tissues, changes in TRH concentrations might be more readily demonstrated when the neurotransmitter environment was altered.…”

“…This work was presented in part at the 63rd Annual Meeting of the Endocrine Society, [17][18][19] June 1981, Cincinnati, Ohio.…”

“…It would therefore appear that the sympathetic nervous system can modify the metabolism of TRH, and that TRH in turn is capable of modulating the function of the sympathetic nervous system. We have recently shown that pancreatic secretion is an important source of TRH in the systemic circulation of the neonatal rat (19). It is therefore possible that alterations in sympathetic nervous system tone could alter the concentration of circulating TRH by an effect at the level of the pancreatic islets.…”

Glucose stimulates and insulin inhibits release of pancreatic TRH in vitro

“…Immunoreactive TRH was later detected in the rat pancreas (3,4) where its concentration, as well as the levels of its messenger RNA, are highest during the neonatal period (5)(6)(7)(8). Within the pancreas, TRH is localized in the insulin-producing B-cells of the islets of Langerhans (9)(10)(11).…”

Histidyl-proline diketopiperazine (His-Pro DKP) immunoreactivity is present in the glucagon-containing cells of the human fetal pancreas.

“…This model offers a number of potential advantages in clarifying the origin of His-Pro DKP. While pancreatic TRH is easily detected in the fetal and early neonatal period in the rat, the levels gradually decline during the neonatal period and are basely detectable in the adult (15)(16)(17)(18). In contrast, the content of His-Pro DKP in the pancreas peaks in the adult rat (12).…”