Synthetic somatostatin analog (octreotide) suppresses daytime growth hormone secretion equivalently in young and older men: preserved pituitary responsiveness to somatostatin's inhibition in aging.
OBJECTIVE
To gain greater insight into the mechanisms controlling the low daytime rate of growth hormone (GH) secretion in older men.


METHODS
We conducted a randomized, controlled study of GH secretion during inhibition by octreotide, a somatostatin analog.


METHODS
Nine young (35-44 years) and ten older (62-79 years) healthy men participated.


METHODS
Octreotide versus nothing, while subjects were on a standardized diet.


METHODS
All subjects were assessed on two separate occasions: baseline and at time of the intervention of octreotide (100 microg subcutaneously); the order of the intervention was randomly assigned. Octreotide was administered at 8:00 a.m. Venous sampling was performed every 10 minutes for 8 hours (8:30 a.m. to 4:30 p.m.). To estimate the joint parameters of pulsatile and basal (between secretory pulses) GH secretion, we used an ultrasensitive chemiluminescence-based GH assay and multiparameter deconvolution analysis.


RESULTS
Compared with baseline, octreotide markedly reduced mean (8-hour) serum GH concentrations in both young (0.585+/-0.255 microg/L vs 0.070+/-0.029 microg/L; P = .008) and older (0.397+/-0.107 microg/L vs 0.087+/-0.027 microg/L; P = 0.005) men. In younger men, octreotide decreased the serum GH concentration primarily by suppressing the mass of GH released per secretory pulse (2.4+/-0.9 microg/L vs 1.0+/-.7 microg/L; P = .015) and the interpulse (basal) rate of GH release (0.0014+/-0.0003 microg/L/min vs 0.0006+/-0.0002 microg/L/min; P = .051). In older men, octreotide also restrained the mass of GH per secretory pulse (1.5+/-0.4 microg/L vs 0.4+/-0.1 microg/L; P = .028) and lowered basal GH release (0.0014+/-0.0003 microg/L/min vs 0.0004+/-0.0001 microg/L/min; P = .007). There were no significant differences when the older men were compared with the young controls.


CONCLUSIONS
Our data suggest that the daytime relative GH deficiency seen in older men is not a result of excessive pituitary susceptibility to the inhibitory capabilities of somatostatin, but more likely reflects impoverished endogenous GHRH drive and/or heightened release of brain somatostatin.
Mulligan
T
T
Virginia Commonwealth University, Hunter Holmes McGuire VA Medical Center, Richmond, USA.
Jaen-Vinuales
A
A
Godschalk
M
M
Iranmanesh
A
A
Veldhuis
J D
JD
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology*; D018709:Statistics, Nonparametric
D019382:Human Growth Hormone; D015282:Octreotide