PATTERN OF THYROTROPIN-RELEASING-HORMONE SECRETION FROM THE ADULT AND NEONATAL RAT PANCREAS - COMPARISON WITH INSULIN-SECRETION

In the present study we examined the secretory pattern of pancreatic TRH. TRH is synthesized in the islets of Langerhans as a high mol wt prohormone, which is then processed to give TRH and several putative pro-TRH fragments. The mature TRH was localized in insulin-containing cells of developing rat pancreas, marked by elevated TRH concentrations. The biological role of pancreatic TRH in the regulation of major pancreatic hormones secretion is still poorly understood. We, therefore, studied TRH release from isolated perfused rat pancreas and from neonatal and adult islets in the absence and presence of glucose and arginine to investigate regulation of TRH secretion compared to that of insulin secretion. The secretory pattern of TRH was the opposite of that of insulin in adult pancreas, but was similar to that of insulin in the developing pancreas, suggesting the presence of a subpopulation of beta-cells with peculiar age-dependent topololgy and/or different intracellular transport for TRH. Additionally, antibodies to two pro-TRH-connecting peptides, pro-TRH-(160-169) and pro-TRH-(178-199), were used to characterize the processing in the developing and the adult rat pancreas. There were parallel age-dependent decreases in TRH and both connecting peptides. Interestingly enough, only pro-TRH-(178-199) was selectively released, suggesting that some of the pro-TRH fragments may also assume biological effects. The establishment of these parameters will allow appropriate screening of the biological response to TRH.