Age and secretagogue type jointly determine dynamic growth hormone responses to exogenous insulin-like growth factor-negative feedback in healthy men.
The primary cause of waning GH and IGF-I concentrations in healthy aging adults is not established. To test the postulate that age influences negative feedback by IGF-I in a secretagogue-specific fashion, 17 normal men (nine young and eight older) each completed eight randomly ordered injections of placebo or recombinant human (rh) IGF-I (20 microg/kg sc), followed by saline/rest, aerobic exercise, GHRH (1 microg/kg iv bolus), or GH-releasing peptide-2 (1 microg/kg iv bolus) stimulation. GH secretion was monitored by sampling blood every 10 min for 7 h, high-sensitivity immunochemiluminometric assay, and deconvolution analysis conditioned on prior pulse-onset times and biexponential kinetics. Analysis of covariance showed that age (P = 0.028), secretagogue (P < 0.001), and rhIGF-I (P < 0.005) individually determine pulsatile GH secretion and exhibit a strong 3-fold interaction (P < 10(-5)). Post hoc comparisons revealed that elderly subjects manifest less IGF-I inhibition of a maximal GHRH stimulus (P = 0.013 vs. young), blunted initial IGF-I suppression of fasting GH release (P = 0.038), and impaired IGF-I feedback on the regularity of GH secretion (P = 0.023). Age stratum did not influence peak IGF-I and nadir GH concentrations or rhIGF-I-induced inhibition of GH secretion stimulated by exercise or GH-releasing peptide-2. In summary, experimental elevation of IGF-I concentrations unmasks reduced rhIGF-I-dependent feedback inhibition of fasting and GHRH-stimulated GH secretion in healthy older men, indicating that aging selectively modulates the autoinhibition process.
Veldhuis
Johannes D
JD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu.
Weltman
Judith Y
JY
Weltman
Arthur L
AL
Iranmanesh
Ali
A
Muller
Eugenio E
EE
Bowers
Cyril Y
CY
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D004311:Double-Blind Method; D005246:Feedback; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone