Synthetic Somatostatin Analog (Octreotide) Suppresses Daytime Growth Hormone Secretion Equivalently in Young and Older Men: Preserved Pituitary Responsiveness to Somatostatin's Inhibition in Aging

Abstract

OBJECTIVE: To gain greater insight into the mechanisms controlling the low daytime rate of growth hormone (GH) secretion in older men. DESIGN: We conducted a randomized, controlled study of GH secretion during inhibition by octreotide, a somatostatin analog. PARTICIPANTS: Nine young (35-44 years) and ten older (62-79 years) healthy men participated. INTERVENTION: Octreotide versus nothing, while subjects were on a standardized diet. MEASUREMENTS: 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.