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

T. W. Redding, A. J. Kastin, D. Gonzalez-Barcena, D. H. Coy, E. J. Coy, D. S. Schalch, Andrew V Schally

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)626-631
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume37
Issue number4
DOIs
StatePublished - 1973
Externally publishedYes

Fingerprint

Metabolism
Gonadotropin-Releasing Hormone
Half-Life
Radioactivity
Urine
Histidine
Injections
Pyrrolidonecarboxylic Acid
Plasmas
Carboxymethylcellulose Sodium
Dipeptides
Chromatography
Bioactivity
Electrophoresis
Dosimetry
Blood
Swine
Body Weight

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 journalArticle

Redding, T. W. ; Kastin, A. J. ; Gonzalez-Barcena, D. ; Coy, D. H. ; Coy, E. J. ; Schalch, D. S. ; Schally, Andrew V. / The half-life, metabolism and excretion of tritiated luteinizing hormone-releasing hormone (Lh-rh) in man. In: Journal of Clinical Endocrinology and Metabolism. 1973 ; Vol. 37, No. 4. pp. 626-631.
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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.",
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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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