The half-life, metabolism and excretion of tritiated luteinizing hormone-releasing hormone (Lh-rh) in man

Synthetic³H-labeled luteinizing hormone-releasing hormone (LH-RH) with a specific activity of 18.3 Ci/mM and the same biological activity as pure porcine LH-RH was used to study the half-life, metabolism and urinary excretion of LH-RH in man. Seven healthy men were given a rapid iv injection of 42 μCi of³H-LH-RH, followed in 6 of the subjects by 250 Hg unlabeled LH-RH. Frequent samples of blood and urine were collected. There was a mean maximum increase in plasma levels of LH of 963% and FSH of 312% in samples obtained 30 min after injection. A plot of the disappearance times in the plasma was characteristic of a multiexponential curve. The half-life of the first exponential curve, which probably represents the half-life of LH-RH in man, was 4 min and for the second curve was 57 min. The distribution volume, when expressed as a percentage of body weight was 8.7%. One hr after the injection of the labeled LH-RH, 48.2 ± 5.4% of the dose of radioactivity was found in the urine and after 24 hr 73.5 ± 5.4% had been excreted. Extraction of the urine followed by chromatography on carboxymethyl cellulose and thin-layer electrophoresis showed most of the radioactivity to be associated with pyroglutamic acid (5-10%) and the dipeptide, pyroglutamyl-histidine (80-90%). None of the radioactivity was found in areas with the same Rf as LH-RH itself. These data suggest that one of the mechanisms for inactivation of LH-RH is the cleavage of pyroglutamyl-histidine moiety from the N-terminus of LH-RH.