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.
Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Johannes D
JD
Veldhuis
Daniel M
DM
Keenan
Joy N
JN
Bailey
Adebordurin M
AM
Adeniji
John M
JM
Miles
Cyril Y
CY
Bowers
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