Effect of aging on the sensitivity of growth hormone secretion to insulin-like growth factor-I negative feedback

• Published in: The journal of clinical endocrinology and metabolism Vol. 82; no. 9; pp. 2996 - 3004
• Main Authors: CHAPMAN, I. M, HARTMAN, M. L, PEZZOLI, S. S, HARRELL, F. E, HINTZ, R. L, ALBERTI, K. G. M. M, THORNER, M. O
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-09-1997
• Subjects: 3-Hydroxybutyric Acid; Adult; Aging - physiology; Biological and medical sciences; Blood Glucose - analysis; Development. Metamorphosis. Moult. Ageing; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified - blood; Feedback; Female; Fundamental and applied biological sciences. Psychology; Glucose - pharmacology; Human Growth Hormone - antagonists & inhibitors; Human Growth Hormone - blood; Human Growth Hormone - secretion; Humans; Hydroxybutyrates - blood; Infusions, Intravenous; Insulin - blood; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Male; Osmolar Concentration; Recombinant Proteins; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Protein hormone; Target tissue resistance; Adenohypophyseal hormone; STH; Hormonal regulation; Feedback regulation; Insulin like growth factor 1; Age; Endocrine secretion
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.82.9.2996

To determine the effect of aging on the suppression of GH secretion by insulin-like growth factor (IGF)-I, we studied 11 healthy young adults (6 men, 5 women, mean +/- SD: 25.2 +/- 4.6 yr old; body mass index 23.7 +/- 1.8 kg/m2) and 11 older adults (6 men, 5 women, 69.5 +/- 5.8 yr old; body mass index 24.2 +/- 2.5 kg/m2). Saline (control) or recombinant human IGF-I (rhIGF-I) (2 h baseline then, in sequence, 2.5 h each of 1, 3, and 10 micrograms/kg.h) was infused iv during the last 9.5 h of a 40.5-h fast; serum glucose was clamped within 15% of baseline. Baseline serum GH concentrations (mean +/- SE: 3.3 +/- 0.7 vs. 1.9 +/- 0.5 micrograms/L, P = 0.02) and total IGF-I concentrations (219 +/- 15 vs. 103 +/- 19 micrograms/L, P < 0.01) were higher in the younger subjects. In both age groups, GH concentrations were significantly decreased by 3 and 10 micrograms/kg.h, but not by 1 microgram/kg.h rhIGF-I. The absolute decrease in GH concentrations was greater in young than in older subjects during the 3 and 10 micrograms/kg.h rhIGF-I infusion periods, but both young and older subjects suppressed to a similar GH level during the last hour of the rhIGF-I infusion (0.78 +/- 0.24 microgram/L and 0.61 +/- 0.16 microgram/L, respectively). The older subjects had a greater increase above baseline in serum concentrations of both total (306 +/- 24 vs. 244 +/- 14 micrograms/L, P = 0.04) and free IGF-I (8.5 +/- 1.4 vs. 4.2 +/- 0.6 micrograms/L, P = 0.01) than the young subjects during rhIGF-I infusion, and their GH suppression expressed in relation to increases in both total and free serum IGF-I concentrations was significantly less than in the young subjects. We conclude that the ability of exogenous rhIGF-I to suppress serum GH concentrations declines with increasing age. This suggests that increased sensitivity to endogenous IGF-I negative feedback is not a cause of the decline in GH secretion that occurs with aging.