Joint mechanisms of impaired growth-hormone pulse renewal in aging men.
BACKGROUND
Aging reduces the size (mass) of GH secretory bursts and thereby reduces total GH secretion. Experimental data indicate that high-amplitude GH pulses are evoked by reversible cycles of GH-induced negative feedback. Whether aging impairs autofeedback is unknown.


OBJECTIVE
The objective of this study is to assess whether age attenuates and IGF-I potentiates negative feedback by a near-physiological pulse of GH.


METHODS
In a university setting, 17 healthy men ages 19-71 yr each underwent four randomly ordered infusion studies on separate mornings fasting.


METHODS
Intravenous injection of a pulse of: 1) saline or 2) recombinant human (rh) GH to impose controlled negative feedback, followed in 2 h by a bolus of 3) saline or (iv) the ghrelin analog GHRP-2 to overcome feedback inhibition.


METHODS
The impact of age and IGF-I concentrations on GH autofeedback was assessed by regression analysis.


RESULTS
Percentage feedback inhibition correlated negatively with: 1) age after consecutive rh GH/saline infusion (R(2) = 0.42, P = 0.005) at any IGF-I concentration; and 2) total IGF-I concentrations after rh GH/GHRP-2 infusion (R(2) = 0.40, P = 0.009) at any age. In contrast, sex-steroid concentrations and body mass index were unrelated to degree of autoinhibition.


CONCLUSIONS
Increased age in healthy men predicts impaired GH autofeedback, which may contribute to attenuated renewal of high-amplitude GH pulses. Conversely, higher IGF-I concentrations in young men forecast accentuated GH autoinhibition, which may drive prominent GH pulses.
Veldhuis
Johannes D
JD
Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Iranmanesh
Ali
A
Bowers
Cyril Y
CY
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D004311:Double-Blind Method; D005246:Feedback; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D011446:Prospective Studies
D009842:Oligopeptides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C091874:growth hormone-releasing peptide-2