Effects of TRH on Pancreatic Growth and Secretion in Rats

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Abstract
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 mgkg of body weighuday) 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 < 0.01), DNA content (+83%, p < 0.01), and protein content (+42%, p < 0.05). Pancreatic enzyme concentrations (Ulmg of DNA) were decreased (amylase, −81%; trypsin, −47%; lipase, −59%, p < 0.01). Absolute rates of amylase discharge (U/mg of DNA) in vitro were reduced in TRH-treated rats (p < 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 < 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. The increase of TRH blood concentrations over a prolonged period of time in the treated group might be explained by a downregulation of the TRH degradation system.

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