Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 626-631 |
| Number of pages | 6 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 37 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1973 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Endocrinology
- Clinical Biochemistry
- Biochemistry, medical
Cite this
The half-life, metabolism and excretion of tritiated luteinizing hormone-releasing hormone (Lh-rh) in man. / Redding, T. W.; Kastin, A. J.; Gonzalez-Barcena, D.; Coy, D. H.; Coy, E. J.; Schalch, D. S.; Schally, Andrew V.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 37, No. 4, 1973, p. 626-631.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The half-life, metabolism and excretion of tritiated luteinizing hormone-releasing hormone (Lh-rh) in man
AU - Redding, T. W.
AU - Kastin, A. J.
AU - Gonzalez-Barcena, D.
AU - Coy, D. H.
AU - Coy, E. J.
AU - Schalch, D. S.
AU - Schally, Andrew V
PY - 1973
Y1 - 1973
N2 - 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.
AB - 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.
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U2 - 10.1210/jcem-37-4-626
DO - 10.1210/jcem-37-4-626
M3 - Article
C2 - 4582574
AN - SCOPUS:0015905910
VL - 37
SP - 626
EP - 631
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -