Persistence of concordant luteinizing hormone (LH), testosterone, and α-subunit pulses after LH-releasing hormone antagonist administrtion in normal men

Spyros N. Pavlou, Johannes D. Veldhuis, Jill Lindner, Kevin H. Souza, Randall Urban, Jean E. Rivier, Wylie W. Vale, David J. Stallard

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

LHRH antagonists suppress pituitary and gonadal function by competing with endogenous LHRH for binding to gonadotroph receptors. To determine the mechanism of suppression of gonadotropin secretion we studied the effects of a single dose of a LHRH antagonist on the pulsatile activity of serum bioactive LH (Bio-LH), immunoreactive LH (IR-LH), α-subunit and testosterone for 24 h in normal men. The LHRH antagonist, Nal-Glu ([Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg 5,DGlu6-(AA),DAla10]LHRH) was given as a single sc injection of 5 mg to five normal men. Blood samples were collected every 10 min during a 10-h baseline period and for 14 h after administration of the antagonist. IR-LH, α-subunit, and testosterone were measured in triplicate, and Bio-LH in duplicate. Pulses were then evaluated using Cluster analysis; all replicates were entered in the pulse analysis. After administration of the Nal-Glu antagonist, IR-LH levels decreased (P < 0.001) from 2.81 ± 0.06 at baseline to a nadir of 0.75 ± 0.02 U/L. Bio-LH levels followed the same pattern, decreasing by 89% (P < 0.001) from 4.54 ± 0.13 to a nadir of 0.51 ± 0.13 U/L 6.8 h after the injection of Nal-Glu. In contrast, serum α-subunit levels did not change (P > 0.05) during the 14-h period after antagonist administration (0.85 ± 0.01 and 0.75 ± 0.01 μg/L before and after Nal-Glu, respectively). Serum testosterone levels decreased by more than 80%, from 17.6 ± 0.2 at baseline to a mean nadir of 3.3 ± 0.7 nmol/L 12.8 h after Nal-Glu administration. Pulse frequency and the number of significant pulses remained the same for all of the measured hormones during the 10-h baseline period and the 14 h after Nal-Glu administration. In contrast, the pulse amplitude of IR-LH, Bio-LH, and testosterone decreased significantly after injection of the antagonist. The pulse amplitude of the α-subunit also declined, albeit not significantly. Coincidence analysis revealed that during both the 10-h baseline and the 14-h post-Nal-Glu period there was a highly significant (P < 10-5) nonrandom synchrony between peaks of IR-LH, Bio-LH, α-subunit, and testosterone. These results suggest that coordinate pulsatile secretion of IR-LH, Bio-LH, and testosterone persists after the administration of 5 mg Nal-Glu LHRH antagonist. These pulses are of low amplitude, resulting in overall reduction of serum gonadotropin and testosterone levels, while α-subunit release remains unaffected. Consequently, we infer that even small amounts of effective endogenous LHRH are sufficient to couple pulsatile hormone release within the hypothalamo-pituitary-gonadal axis in men.

Original languageEnglish (US)
Pages (from-to)1472-1478
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume70
Issue number5
StatePublished - May 1990
Externally publishedYes

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Hormone Antagonists
Luteinizing Hormone
Gonadotropin-Releasing Hormone
Testosterone
Gonadotropins
Serum
Hormones
Gonadotrophs
Injections
Cluster analysis
2-naphthylalanyl-glutamic acid
Cluster Analysis
Blood

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Persistence of concordant luteinizing hormone (LH), testosterone, and α-subunit pulses after LH-releasing hormone antagonist administrtion in normal men. / Pavlou, Spyros N.; Veldhuis, Johannes D.; Lindner, Jill; Souza, Kevin H.; Urban, Randall; Rivier, Jean E.; Vale, Wylie W.; Stallard, David J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 70, No. 5, 05.1990, p. 1472-1478.

Research output: Contribution to journalArticle

Pavlou, Spyros N. ; Veldhuis, Johannes D. ; Lindner, Jill ; Souza, Kevin H. ; Urban, Randall ; Rivier, Jean E. ; Vale, Wylie W. ; Stallard, David J. / Persistence of concordant luteinizing hormone (LH), testosterone, and α-subunit pulses after LH-releasing hormone antagonist administrtion in normal men. In: Journal of Clinical Endocrinology and Metabolism. 1990 ; Vol. 70, No. 5. pp. 1472-1478.
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abstract = "LHRH antagonists suppress pituitary and gonadal function by competing with endogenous LHRH for binding to gonadotroph receptors. To determine the mechanism of suppression of gonadotropin secretion we studied the effects of a single dose of a LHRH antagonist on the pulsatile activity of serum bioactive LH (Bio-LH), immunoreactive LH (IR-LH), α-subunit and testosterone for 24 h in normal men. The LHRH antagonist, Nal-Glu ([Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg 5,DGlu6-(AA),DAla10]LHRH) was given as a single sc injection of 5 mg to five normal men. Blood samples were collected every 10 min during a 10-h baseline period and for 14 h after administration of the antagonist. IR-LH, α-subunit, and testosterone were measured in triplicate, and Bio-LH in duplicate. Pulses were then evaluated using Cluster analysis; all replicates were entered in the pulse analysis. After administration of the Nal-Glu antagonist, IR-LH levels decreased (P < 0.001) from 2.81 ± 0.06 at baseline to a nadir of 0.75 ± 0.02 U/L. Bio-LH levels followed the same pattern, decreasing by 89{\%} (P < 0.001) from 4.54 ± 0.13 to a nadir of 0.51 ± 0.13 U/L 6.8 h after the injection of Nal-Glu. In contrast, serum α-subunit levels did not change (P > 0.05) during the 14-h period after antagonist administration (0.85 ± 0.01 and 0.75 ± 0.01 μg/L before and after Nal-Glu, respectively). Serum testosterone levels decreased by more than 80{\%}, from 17.6 ± 0.2 at baseline to a mean nadir of 3.3 ± 0.7 nmol/L 12.8 h after Nal-Glu administration. Pulse frequency and the number of significant pulses remained the same for all of the measured hormones during the 10-h baseline period and the 14 h after Nal-Glu administration. In contrast, the pulse amplitude of IR-LH, Bio-LH, and testosterone decreased significantly after injection of the antagonist. The pulse amplitude of the α-subunit also declined, albeit not significantly. Coincidence analysis revealed that during both the 10-h baseline and the 14-h post-Nal-Glu period there was a highly significant (P < 10-5) nonrandom synchrony between peaks of IR-LH, Bio-LH, α-subunit, and testosterone. These results suggest that coordinate pulsatile secretion of IR-LH, Bio-LH, and testosterone persists after the administration of 5 mg Nal-Glu LHRH antagonist. These pulses are of low amplitude, resulting in overall reduction of serum gonadotropin and testosterone levels, while α-subunit release remains unaffected. Consequently, we infer that even small amounts of effective endogenous LHRH are sufficient to couple pulsatile hormone release within the hypothalamo-pituitary-gonadal axis in men.",
author = "Pavlou, {Spyros N.} and Veldhuis, {Johannes D.} and Jill Lindner and Souza, {Kevin H.} and Randall Urban and Rivier, {Jean E.} and Vale, {Wylie W.} and Stallard, {David J.}",
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T1 - Persistence of concordant luteinizing hormone (LH), testosterone, and α-subunit pulses after LH-releasing hormone antagonist administrtion in normal men

AU - Pavlou, Spyros N.

AU - Veldhuis, Johannes D.

AU - Lindner, Jill

AU - Souza, Kevin H.

AU - Urban, Randall

AU - Rivier, Jean E.

AU - Vale, Wylie W.

AU - Stallard, David J.

PY - 1990/5

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N2 - LHRH antagonists suppress pituitary and gonadal function by competing with endogenous LHRH for binding to gonadotroph receptors. To determine the mechanism of suppression of gonadotropin secretion we studied the effects of a single dose of a LHRH antagonist on the pulsatile activity of serum bioactive LH (Bio-LH), immunoreactive LH (IR-LH), α-subunit and testosterone for 24 h in normal men. The LHRH antagonist, Nal-Glu ([Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg 5,DGlu6-(AA),DAla10]LHRH) was given as a single sc injection of 5 mg to five normal men. Blood samples were collected every 10 min during a 10-h baseline period and for 14 h after administration of the antagonist. IR-LH, α-subunit, and testosterone were measured in triplicate, and Bio-LH in duplicate. Pulses were then evaluated using Cluster analysis; all replicates were entered in the pulse analysis. After administration of the Nal-Glu antagonist, IR-LH levels decreased (P < 0.001) from 2.81 ± 0.06 at baseline to a nadir of 0.75 ± 0.02 U/L. Bio-LH levels followed the same pattern, decreasing by 89% (P < 0.001) from 4.54 ± 0.13 to a nadir of 0.51 ± 0.13 U/L 6.8 h after the injection of Nal-Glu. In contrast, serum α-subunit levels did not change (P > 0.05) during the 14-h period after antagonist administration (0.85 ± 0.01 and 0.75 ± 0.01 μg/L before and after Nal-Glu, respectively). Serum testosterone levels decreased by more than 80%, from 17.6 ± 0.2 at baseline to a mean nadir of 3.3 ± 0.7 nmol/L 12.8 h after Nal-Glu administration. Pulse frequency and the number of significant pulses remained the same for all of the measured hormones during the 10-h baseline period and the 14 h after Nal-Glu administration. In contrast, the pulse amplitude of IR-LH, Bio-LH, and testosterone decreased significantly after injection of the antagonist. The pulse amplitude of the α-subunit also declined, albeit not significantly. Coincidence analysis revealed that during both the 10-h baseline and the 14-h post-Nal-Glu period there was a highly significant (P < 10-5) nonrandom synchrony between peaks of IR-LH, Bio-LH, α-subunit, and testosterone. These results suggest that coordinate pulsatile secretion of IR-LH, Bio-LH, and testosterone persists after the administration of 5 mg Nal-Glu LHRH antagonist. These pulses are of low amplitude, resulting in overall reduction of serum gonadotropin and testosterone levels, while α-subunit release remains unaffected. Consequently, we infer that even small amounts of effective endogenous LHRH are sufficient to couple pulsatile hormone release within the hypothalamo-pituitary-gonadal axis in men.

AB - LHRH antagonists suppress pituitary and gonadal function by competing with endogenous LHRH for binding to gonadotroph receptors. To determine the mechanism of suppression of gonadotropin secretion we studied the effects of a single dose of a LHRH antagonist on the pulsatile activity of serum bioactive LH (Bio-LH), immunoreactive LH (IR-LH), α-subunit and testosterone for 24 h in normal men. The LHRH antagonist, Nal-Glu ([Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg 5,DGlu6-(AA),DAla10]LHRH) was given as a single sc injection of 5 mg to five normal men. Blood samples were collected every 10 min during a 10-h baseline period and for 14 h after administration of the antagonist. IR-LH, α-subunit, and testosterone were measured in triplicate, and Bio-LH in duplicate. Pulses were then evaluated using Cluster analysis; all replicates were entered in the pulse analysis. After administration of the Nal-Glu antagonist, IR-LH levels decreased (P < 0.001) from 2.81 ± 0.06 at baseline to a nadir of 0.75 ± 0.02 U/L. Bio-LH levels followed the same pattern, decreasing by 89% (P < 0.001) from 4.54 ± 0.13 to a nadir of 0.51 ± 0.13 U/L 6.8 h after the injection of Nal-Glu. In contrast, serum α-subunit levels did not change (P > 0.05) during the 14-h period after antagonist administration (0.85 ± 0.01 and 0.75 ± 0.01 μg/L before and after Nal-Glu, respectively). Serum testosterone levels decreased by more than 80%, from 17.6 ± 0.2 at baseline to a mean nadir of 3.3 ± 0.7 nmol/L 12.8 h after Nal-Glu administration. Pulse frequency and the number of significant pulses remained the same for all of the measured hormones during the 10-h baseline period and the 14 h after Nal-Glu administration. In contrast, the pulse amplitude of IR-LH, Bio-LH, and testosterone decreased significantly after injection of the antagonist. The pulse amplitude of the α-subunit also declined, albeit not significantly. Coincidence analysis revealed that during both the 10-h baseline and the 14-h post-Nal-Glu period there was a highly significant (P < 10-5) nonrandom synchrony between peaks of IR-LH, Bio-LH, α-subunit, and testosterone. These results suggest that coordinate pulsatile secretion of IR-LH, Bio-LH, and testosterone persists after the administration of 5 mg Nal-Glu LHRH antagonist. These pulses are of low amplitude, resulting in overall reduction of serum gonadotropin and testosterone levels, while α-subunit release remains unaffected. Consequently, we infer that even small amounts of effective endogenous LHRH are sufficient to couple pulsatile hormone release within the hypothalamo-pituitary-gonadal axis in men.

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