Determinants of GH-releasing hormone and GH-releasing peptide synergy in men


Age, sex steroids, and abdominal-visceral fat (AVF) jointly affect pulsatile growth hormone (GH) secretion. Pulsatile GH secretion in turn is controlled by GH-releasing hormone (GHRH), GH-releasing peptide (GHRP), and somatostatin. Marked stimulation of pulsatile GH secretion is achieved via GHRH-GHRP synergy. Nonetheless, how key modulators of GH secretion, such as age, sex steroids, and body mass index, modify GHRH-GHRP synergy is not known. The present strategy was to 1) infuse GHRH and GHRP-2 simultaneously to evoke synergy and 2) downregulate the gonadal axis with leuprolide and then restore placebo (Pl) or testosterone (T) to clamp the sex steroid milieu. Forty-seven men [18–74 yr of age, T = 7–1,950 ng/dl, estradiol (E2) = 5–79 pg/ml, insulin-like growth factor (IGF)-I = 115–817 μg/l, AVF = 11–349 cm2] were studied. GHRH-GHRP synergy correlated negatively with age and AVF (both P < 0.001) and positively with IGF-I (P < 0.001) and IGF-binding protein (IGFBP)-3 (P = 0.031). Unstimulated basal (nonpulsatile) GH secretion correlated positively with T (P = 0.015) and E2 (P = 0.004) concentrations. Fasting pulsatile GH secretion varied negatively with age (P = 0.017) and positively with IGF-I (P = 0.002) and IGFBP-3 (P = 0.001). By stepwise forward-selection multivariate analyses, AVF, IGF-I, and IGFBP-3 together explained 60% of the variability in GHRH-GHRP synergy (P < 0.001), E2 accounted for 17% of the variability in basal GH secretion (P = 0.007), and IGF-I explained 20% of the variability in fasting pulsatile GH secretion (P = 0.002). In conclusion, a paradigm examining GHRH-GHRP synergy under a sex steroid clamp reveals highly selective control of basal, pulsatile, and synergistic peptide-driven GH secretion by AVF, E2, and IGF-I in healthy men

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This paper was published in PubMed Central.

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