Intra- and extravascular turnover of thyrotrophin-releasing hormone in normal man

In 14 normal subjects constant TRH infusions for determination of plasma clearance rate (PCR) and half-life of disappearance (t 1/2) of TRH were carried out with simultaneous determination of half-life of disappearance of TRH in serum in vitro (t 1/2p). PCR, t 1/2 and t 1/2p were 1532 +/- 423 ml/min, 6.6 +/- 1.5 min and 16.8 +/- 9.4 min respectively (mean +/- S.D.) and displayed only minor fluctuations when determined repeatedly in the same subjects (coefficients of variation within individuals were 15.1, 10.6 and 7.5% respectively). Simultaneous determination of PCR, t 1/2 and t 1/2p enabled calculation of the half-life of disappearance of TRH in the extravascular tissue compartment (t 1/2t). Values of t 1/2t (6.3 +/- 1.4 min) correlated to t 1/2p (r = 0.95). Activities of TRH-degrading enzymes in tissues and in serum were independent of sex, phase of female menstrual cycle, time of day and of the concentrations of TRH used. The methods employed for this investigation offer the possibility of examining the degradation of TRH and TRH analogues both in the serum and in the extravascular compartment during various conditions.