Thyrotropin-releasing hormone (TRH) has been shown to be scattered throughout the gastrointestinal tract. High concentrations of TRH are reported in the pancreas of animals and humans. The present study was designed to investigate the pattern of pancreatic adaptation following chronic TRH administration in rats. Ten male Wistar rats were injected daily at 8.00 and 16.00 h with TRH (total dose of 6 mg/kg of body weight/day) via a chronic gastric fistula. Ten pair-fed control animals were injected with a saline solution. After 10 days, the rats were killed after an overnight fast; pancreatic wet weight, DNA, protein, amylase, trypsin, and lipase content were determined. Blood TRH levels were measured using a specific RIA (TRH antiserum K2B7, normal range of 30-80 fmol/ml). TRH increased pancreatic wet weight (+70%, p less than 0.01), DNA content (+83%, p less than 0.01), and protein content (+42%, p less than 0.05). Pancreatic enzyme concentrations (U/mg of DNA) were decreased (amylase, -81%; trypsin, -47%; lipase, -59%, p less than 0.01). Absolute rates of amylase discharge (U/mg of DNA) in vitro were reduced in TRH-treated rats (p less than 0.01) but the relative amount of basal and stimulated amylase discharge (% of total) was not influenced by TRH. Blood TRH levels were significantly increased (324 +/- 53 vs. 48 +/- 6 fmol/ml, p less than 0.01) 12 h after the last TRH administration. These data indicate that chronic TRH administration in rats induces pancreatic hyperplasia but decreases the pancreatic concentration of digestive enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)