Effect of aging on the sensitivity of growth hormone secretion to insulin-like growth factor-I negative feedback.
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.
Chapman
I M
IM
Department of Medicine, University of Virginia Health Sciences Center, USA. ichapman@medicine.adelaide.edu.au
Hartman
M L
ML
Pezzoli
S S
SS
Harrell
F E
FE
Hintz
R L
RL
Alberti
K G
KG
Thorner
M O
MO
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005246:Feedback; D005260:Female; D005947:Glucose / Q000494:pharmacology; D019382:Human Growth Hormone / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D011994:Recombinant Proteins
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D020155:3-Hydroxybutyric Acid