TRH pharmacokinetics and nerve stimulation evoked prostatic fluid secretion during TRH infusion in the dog

Abstract

The pharmacokinetics of TRH have been determined in man and the rat as well as other species whose serum contains TRH degrading enzymes, TRH pharmacokinetics have not been determined in the dog. This species is unusual in that its serum contains little or no TRH degrading activity. TRH pharmacokinetics were determined from measurements of plasma TRH concentrations during and following a 1-h infusion of TRH, 20 micrograms.kg-1.min-1, into dogs bearing prostatic urethral cannula. During TRH administration prostatic fluid secretion was evoked by hypogastric nerve stimulation and the content of TRH immunoreactive material in prostatic fluid was determined. Prostatic fluid was also collected after hypogastric nerve stimulation in dogs that did not receive TRH infusion. The TRH plasma profile in TRH-infused dogs exhibited two-compartment characteristics with an initial half-time of 10.4 +/- 5.4 (mean +/- SD) min, a terminal half-time of 69.4 +/- 24 min, and a metabolic clearance rate of 7.64 +/- 4.48 ml.min-1.kg-1. These findings suggest that the half-time of TRH is longer, and its metabolic clearance rate is less, in the dog than in humans or rats. TRH administration was not associated with altered nerve induced prostatic fluid secretion. Prostatic fluid samples contained TRH immunoreactive material regardless of whether they were collected after epithelial cell stimulation with pilocarpine, or after hypogastric nerve stimulation. In contrast to previous results with vasoactive intestinal peptide, TRH does not acutely alter prostatic fluid secretion. As has been reported for prostatic tissue extracts, immunoreactive material is present in prostatic fluid and appears to arise from epithelial cells.