Preservation of GHRH and GH-releasing peptide-2 efficacy in young men with experimentally induced hypogonadism

Johannes D Veldhuis, Daniel M. Keenan, Joy N. Bailey, John M. Miles, Cyril Y. Bowers

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Somatostatin (SS), GHRH, GH-releasing peptide (GHRP), and the sex-steroid milieu regulate GH secretion. Objective: To test whether GHRH and GHRP remain effective secretagogs in the face of short-term hypogonadism. Design: Prospective, randomized double-blind. Methods: Healthy young men (n = 24) received a GnRH agonist twice 3 weeks apart followed by placebo (n = 13, Pl) or testosterone (n = 11, testosterone) addback. Subjects were then given consecutive i.v. infusions of L-arginine (to restrain SS outflow) and a maximally effective dose of GHRH or GHRP-2 (to test corresponding secretagog pathways). Results: GH secretion stimulated by L-arginine/GHRH and by L-arginine/GHRP-2 was unaffected by combined testosterone/estradiol (E 2) depletion. The low testosterone/E2 milieu decreased basal (nonpulsatile) GH secretion (P = 0.038), without altering fasting pulsatile GH secretion or IGF1 or IGF-binding protein (IGFBP)-3 concentrations. IGFBP-1 (P < 0.0001) and abdominal visceral fat (AVF, P = 0.017) correlated negatively with fasting basal GH secretion. By contrast, IGF1 (P = 0.0012) and IGFBP-3 (P = 0.015) correlated positively with fasting pulsatile GH secretion. AVF (P = 0.0024) was a negative determinant, and IGF1 a positive determinant (P = 0.018), of GHRH-driven GH pulses. Responses to GHRP-2 were unrelated to any of these factors. Conclusion: L-arginine/GHRP-2 appears to be an especially robust stimulus of GH secretion, since efficacy is unmodified by profound short-term hypogonadism, a range of AVF estimates, and a spectrum of IGF1, IGFBP-1, and IGFBP-3 concentrations. Whether robustness also applies to chronic hypogonadism is not known.

Original languageEnglish (US)
Pages (from-to)293-300
Number of pages8
JournalEuropean Journal of Endocrinology
Volume161
Issue number2
DOIs
StatePublished - 2009

Fingerprint

Hypogonadism
Peptides
Insulin-Like Growth Factor Binding Protein 3
Arginine
Testosterone
Insulin-Like Growth Factor Binding Protein 1
Fasting
Somatostatin
Intra-Abdominal Fat
Gonadotropin-Releasing Hormone
Estradiol
Steroids
Placebos

ASJC Scopus subject areas

  • Endocrinology
  • Medicine(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Preservation of GHRH and GH-releasing peptide-2 efficacy in young men with experimentally induced hypogonadism. / Veldhuis, Johannes D; Keenan, Daniel M.; Bailey, Joy N.; Miles, John M.; Bowers, Cyril Y.

In: European Journal of Endocrinology, Vol. 161, No. 2, 2009, p. 293-300.

Research output: Contribution to journalArticle

Veldhuis, Johannes D ; Keenan, Daniel M. ; Bailey, Joy N. ; Miles, John M. ; Bowers, Cyril Y. / Preservation of GHRH and GH-releasing peptide-2 efficacy in young men with experimentally induced hypogonadism. In: European Journal of Endocrinology. 2009 ; Vol. 161, No. 2. pp. 293-300.
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abstract = "Background: Somatostatin (SS), GHRH, GH-releasing peptide (GHRP), and the sex-steroid milieu regulate GH secretion. Objective: To test whether GHRH and GHRP remain effective secretagogs in the face of short-term hypogonadism. Design: Prospective, randomized double-blind. Methods: Healthy young men (n = 24) received a GnRH agonist twice 3 weeks apart followed by placebo (n = 13, Pl) or testosterone (n = 11, testosterone) addback. Subjects were then given consecutive i.v. infusions of L-arginine (to restrain SS outflow) and a maximally effective dose of GHRH or GHRP-2 (to test corresponding secretagog pathways). Results: GH secretion stimulated by L-arginine/GHRH and by L-arginine/GHRP-2 was unaffected by combined testosterone/estradiol (E 2) depletion. The low testosterone/E2 milieu decreased basal (nonpulsatile) GH secretion (P = 0.038), without altering fasting pulsatile GH secretion or IGF1 or IGF-binding protein (IGFBP)-3 concentrations. IGFBP-1 (P < 0.0001) and abdominal visceral fat (AVF, P = 0.017) correlated negatively with fasting basal GH secretion. By contrast, IGF1 (P = 0.0012) and IGFBP-3 (P = 0.015) correlated positively with fasting pulsatile GH secretion. AVF (P = 0.0024) was a negative determinant, and IGF1 a positive determinant (P = 0.018), of GHRH-driven GH pulses. Responses to GHRP-2 were unrelated to any of these factors. Conclusion: L-arginine/GHRP-2 appears to be an especially robust stimulus of GH secretion, since efficacy is unmodified by profound short-term hypogonadism, a range of AVF estimates, and a spectrum of IGF1, IGFBP-1, and IGFBP-3 concentrations. Whether robustness also applies to chronic hypogonadism is not known.",
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