Age and secretagogue type jointly determine dynamic growth hormone responses to exogenous insulin-like growth factor-negative feedback in healthy men

Johannes D. Veldhuis, Judith Y. Weltman, Arthur L. Weltman, Ali Iranmanesh, Eugenio E. Muller, Cyril Y. Bowers

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 μg/kg sc), followed by saline/rest, aerobic exercise, GHRH (1 μg/kg iv bolus), or GH-releasing peptide-2 (1 μg/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.

Original languageEnglish (US)
Pages (from-to)5542-5548
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number11
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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