Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy.
OBJECTIVE
Testosterone supplementation increases GH and IGF-I concentrations in healthy older men via unknown mechanisms. We examine the hypotheses that (i) testosterone amplifies stimulation of GH secretion by GH-releasing peptide (GHRP)-2 or GH-releasing hormone (GHRH) infused with l-arginine to limit somatostatin outflow (i.e. upregulates each agonistic pathway), (ii) testosterone augments the effect of both peptidyl secretagogues infused together (i.e. reduces opposition by hypothalamic somatostatin) and (iii) abdominal visceral fat (AVF) mass is a negative determinant of specific secretagogue-stimulated GH secretion.


METHODS
Randomized double-blind crossover design of placebo versus testosterone administration in healthy older men.


METHODS
Deconvolution analysis was used to estimate basal GH secretion and the mass (integral) and waveform (time-shape) of GH secretory bursts.


RESULTS
Statistical contrasts revealed that administration of testosterone compared with placebo in seven men aged 60-77 years increased fasting concentrations of GH (P < 0.01) and IGF-I (P = 0.003), and basal (P < 0.005) and pulsatile (P < 0.01) GH secretion. Testosterone did not alter the absolute value or rank order of secretagogue efficacy: l-arginine/GHRP-2 (23-fold effect over saline) = GHRH/GHRP-2 (20-fold) > l-arginine/GHRH (7.5-fold). Waveform reconstruction indicated that each stimulus pair accelerated initial GH secretion within a burst (P < 0.01). Regression analysis disclosed a significant inverse association between GH secretory-burst mass and computer tomography-estimated AVF following stimulation with l-arginine/GHRH after testosterone supplementation (R(2) = 0.54, P = 0.015).


CONCLUSIONS
Supraphysiological testosterone concentrations augment GH and IGF-I production in the elderly male without altering maximal somatotrope responses to single and combined GHRH and GHRP-2 drive, thus predicting multifactorial mechanisms of testosterone upregulation.
Veldhuis
Johannes D
JD
Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, MN 55905, USA. veldhuis.johannes@mayo.edu
Keenan
Daniel M
DM
Mielke
Kristi
K
Miles
John M
JM
Bowers
Cyril Y
CY
D000273:Adipose Tissue / Q000000981:diagnostic imaging; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D011860:Radiography, Abdominal; D012371:Robotics; D013739:Testosterone / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed; D014781:Viscera / Q000000981:diagnostic imaging
D004338:Drug Combinations; D009842:Oligopeptides; D019382:Human Growth Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; C091874:growth hormone-releasing peptide-2