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

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 (nZ24) received a GnRH agonist twice 3 weeks apart followed by placebo (nZ13, Pl) or testosterone (nZ11, 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/E 2 milieu decreased basal (nonpulsatile) GH secretion (PZ0.038), without altering fasting pulsatile GH secretion or IGF1 or IGFbinding protein (IGFBP)-3 concentrations. IGFBP-1 (P!0.0001) and abdominal visceral fat (AVF, PZ0.017) correlated negatively with fasting basal GH secretion. By contrast, IGF1 (PZ0.0012) and IGFBP-3 (PZ0.015) correlated positively with fasting pulsatile GH secretion. AVF (PZ0.0024) was a negative determinant, and IGF1 a positive determinant (PZ0.018), 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.

Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males

“…Veldhuis et al conducted a prospective, randomized double blind trial to further evaluate the effects of GHRH and GHRP-2 in 24 healthy young men with experimentally induced hypogonadism (42). All 24 men were given 2 injections of depot leuprolide acetate three weeks apart, following which 13 men were given saline and 11 were given 200 mg testosterone enanthate weekly for 3 doses.…”

Confiscated black market products and nutritional supplements with non‐approved ingredients analyzed in the cologne doping control laboratory 2009

“…One of the products was labelled to contain GHRP‐2 (His‐D‐β‐Nal‐Ala‐Trp‐D‐Phe‐Lys‐OCH 3 ) and three other natural growth hormone releasers namely Arginine Pyroglutamate, (2S)‐2‐aminopentanedioic acid and L‐alpha glycerylphosphorylcholine (Table 1, 2a). The combination of Arginine and GHRP‐2 was described as an especially robust stimulus for growth hormone secretion in administration studies in growth‐hormone‐deficient children 20…”

Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers

“…In one small proof-of-principle physiology study, untreated hypogonadal men had an intact IGF1 response to GH stimulation, and this response was unchanged by cross-over treatment with both testosterone and dihydrotestosterone administered as transdermal gel ( Gleeson and Shalet, 2009 ). Supporting this finding, acute hypogonadism induced by GnRH agonist therapy in healthy men did not result in blunting of the GH response to dynamic stimulation, although basal GH secretion was marginally reduced ( Veldhuis et al, 2009 ). On the basis of these limited data, it appears unlikely that the GH-IGF1 axis plays a direct role in the mediation of loss of muscle mass associated with hypogonadism.…”