Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp.
BACKGROUND
Sex steroids influence GH secretion in complex ways.


OBJECTIVE
Analyses in a low sex-steroid milieu will help unveil the effects of age and other nonsteroidal regulators on GH secretion.


BACKGROUND
The study was conducted in a tertiary medical center.


METHODS
The study group included 13 healthy young men and 12 healthy older men.


METHODS
We used GnRH agonist-induced down-regulation of testosterone and estradiol secretion, followed by consecutive infusion of l-arginine and GHRH or GHRP-2, to test secretagogue efficacies.


RESULTS
We measured basal and pulsatile GH secretion.


RESULTS
During experimental testosterone/estradiol deprivation, older (57 +/- 1.7 yr) men maintained: 1) 6.8-fold less pulsatile GH secretion (P < 0.001); and 2) 2-fold lower maximal GH responses to GHRH (P = 0.0065) and GHRP-2 (P = 0.022) than young (23 +/- 1.1 yr old) individuals. Stepwise forward-selection regression analyses identified: 1) abdominal visceral fat as a dominant negative predictor of both GHRH (R(2) = 0.49; P = 0.001) and GHRP-2 (R(2) = 0.38; P = 0.005) efficacies; and 2) fasting IGF-I concentration as a major positive correlate of GHRH (R(2) = 0.52; P < 0.001) and GHRP-2 (R(2) = 0.31; P = 0.018) efficacies. Unstimulated pulsatile GH secretion was jointly correlated with IGF-I and IGFBP-3 (P = 0.039).


CONCLUSIONS
Measures of body composition (abdominal visceral fat) and pulsatile GH action (IGF-I) explain up to one half of interindividual variability in the efficacies of GHRH and GHRP-2 in sex steroid-depleted men. Accordingly, normative ranges for maximal single peptide-stimulated GH secretion in short-term hypogonadal states should incorporate the influence of these determinants as well as age.
Veldhuis
Johannes D
JD
Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Keenan
Daniel M
DM
Bailey
Joy N
JN
Adeniji
Adebordurin M
AM
Miles
John M
JM
Bowers
Cyril Y
CY
D050154:Adiposity / Q000502:physiology; D000328:Adult; D000375:Aging / Q000502:physiology*; D015331:Cohort Studies; D004311:Double-Blind Method; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D050152:Intra-Abdominal Fat / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
D018969:Insulin-Like Growth Factor Binding Proteins; D009842:Oligopeptides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; C091874:growth hormone-releasing peptide-2