TY - JOUR
T1 - Testosterone supplementation in older men restrains insulin-like growth factor's dose-dependent feedback inhibition of pulsatile growth hormone secretion
AU - Veldhuis, Johannes D.
AU - Keenan, Daniel M.
AU - Bailey, Joy N.
AU - Adeniji, Adenborduin
AU - Miles, John M.
AU - Paulo, Remberto
AU - Cosma, Mihaela
AU - Soares-Welch, Cacia
N1 - Funding Information:
This work was supported in part via the Clinical Translational Science Center Grant 1 UL 1 RR024150 to the Mayo Clinic and Foundation from the National Center for Research Resources (Rockville, MD) and by Grants R01 NIA AG29362 and AG19695 from the National Institutes of Health (Bethesda, MD).
PY - 2009/1
Y1 - 2009/1
N2 - Background: Pulsatile GH secretion declines in older men. The causal mechanisms are unknown. Candidates include deficient feedforward (stimulation) by endogenous secretagogues and excessive feedback (inhibition) by GH or IGF-I due to age and/or relative hypoandrogenemia. Hypothesis: Testosterone (T) supplementation in healthy older men will restrain negative feedback by systemic concentrations of IGF-I. Subjects: Twenty-four healthy men(ages, 50 to 75 yr; body mass index, 24 to 30 kg/m2) participated in the study. Methods: We performed a prospectively randomized, double-blind, placebo-controlled assessment of the impact of pharmacological T supplementation on GH responses to randomly ordered separate-day injections of recombinant human IGF-I doses of 0, 1.0, 1.5, and 2.0 mg/m2. Analysis: Deconvolution and approximate entropy analyses of pulsatile, basal, and entropic (pattern-sensitive) modes of GH secretion were conducted. Results: Recombinant human IGF-I injections 1) elevated mean and peak serum IGF-I concentrations dose-dependently (both P < 0.001); 2) suppressed pulsatile GH secretion (P = 0.003), burst mass (P=0.025), burst number (P=0.005), interpulse variability (P=0.032), and basal GH secretion (P=0.009); and 3) increased secretory pattern regularity (P=0.020). T administration did not alter experimentally controlled IGF-I concentrations, but it elevated mean GH concentrations (P=0.015) and stimulated pulsatile GH secretion (frequency P = 0.037, mass per burst P = 0.038). Compared with placebo, T attenuated exogenous IGF-I's inhibition of GH secretory-burst mass (P < 0.038) without restoring pulse number, basal secretion, or pattern regularity. Conclusion: The capability of systemic T to mute IGF-I feedback on pulsatile GH secretion suggests a novel mechanism for augmenting GH production.
AB - Background: Pulsatile GH secretion declines in older men. The causal mechanisms are unknown. Candidates include deficient feedforward (stimulation) by endogenous secretagogues and excessive feedback (inhibition) by GH or IGF-I due to age and/or relative hypoandrogenemia. Hypothesis: Testosterone (T) supplementation in healthy older men will restrain negative feedback by systemic concentrations of IGF-I. Subjects: Twenty-four healthy men(ages, 50 to 75 yr; body mass index, 24 to 30 kg/m2) participated in the study. Methods: We performed a prospectively randomized, double-blind, placebo-controlled assessment of the impact of pharmacological T supplementation on GH responses to randomly ordered separate-day injections of recombinant human IGF-I doses of 0, 1.0, 1.5, and 2.0 mg/m2. Analysis: Deconvolution and approximate entropy analyses of pulsatile, basal, and entropic (pattern-sensitive) modes of GH secretion were conducted. Results: Recombinant human IGF-I injections 1) elevated mean and peak serum IGF-I concentrations dose-dependently (both P < 0.001); 2) suppressed pulsatile GH secretion (P = 0.003), burst mass (P=0.025), burst number (P=0.005), interpulse variability (P=0.032), and basal GH secretion (P=0.009); and 3) increased secretory pattern regularity (P=0.020). T administration did not alter experimentally controlled IGF-I concentrations, but it elevated mean GH concentrations (P=0.015) and stimulated pulsatile GH secretion (frequency P = 0.037, mass per burst P = 0.038). Compared with placebo, T attenuated exogenous IGF-I's inhibition of GH secretory-burst mass (P < 0.038) without restoring pulse number, basal secretion, or pattern regularity. Conclusion: The capability of systemic T to mute IGF-I feedback on pulsatile GH secretion suggests a novel mechanism for augmenting GH production.
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U2 - 10.1210/jc.2008-1516
DO - 10.1210/jc.2008-1516
M3 - Article
C2 - 18984660
AN - SCOPUS:58149392536
SN - 0021-972X
VL - 94
SP - 246
EP - 254
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -