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Clinical Research Center Studies |
Department of Medicine, Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center (S.E.K., M.L.H., S.S.P., M.O.T.), Charlottesville, Virginia 22908; University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School (S.R.S., J.R.S.), New Brunswick, New Jersey 08903; and Merck Research Laboratories (B.J.G., J.M.W., D.A.K.), Rahway, New Jersey 07065
Address all correspondence and requests for reprints to: Dr. Michael O. Thorner, Department of Medicine, Box 511–66, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908. E-mail MOT{at}virginia.edu
Abstract
GH secretion and the response to GH secretagogues are significantly
diminished in obese individuals. Previous studies have shown that
L-692,429 (L), a nonpeptide mimetic of GH-releasing peptide,
selectively stimulates GH release in normal young men and in the
elderly, who also have diminished GH secretion. A paired, two-site
study examined the effects of L on GH release in 12 healthy obese (part
A; mean ± SD: age, 26.1 ± 3.3 yr; body mass
index, 35.0 ± 3.1 kg/m2) and 10 nonobese (part B;
age, 22.2 ± 2.3 yr; body mass index, 
27.0) young men. In part
A, placebo, low dose L (0.2 mg/kg), or high dose L (0.75 mg/kg) was
administered iv over 15 min on 3 separate occasions after an overnight
fast. Samples for GH, PRL, and cortisol determinations were obtained
every 15 min. GH release (mean ± SE) was
significantly increased by both doses of L compared to the effect of
placebo: 12.6 ± 1.8 µg/L (low dose), 18.5 ± 2.7 µg/L
(high dose), and 0.84 ± 0.1 µg/L (placebo), respectively
(P < 0.05). In a subset of 6 obese men, in samples
collected every 5 min, the GH response to both doses of L was
significantly greater than that to 1 µg/kg GHRH. To compare the
response to low dose L in the obese and to determine the effects of
feeding on this response, 0.2 mg/kg L was administered as described in
part A to nonobese young men after an overnight fast (fasted) or a
standardized breakfast (fed; part B). Low dose L was an effective GH
secretagogue in nonobese young men; however, this effect was attenuated
with feeding [43.6 ± 7.9 (fasted) vs. 17.7
± 4.8 (fed)µg/L]. Of note, the response to low dose L in fasted
obese individuals was similar to that in fed nonobese individuals. The
administration of L was well tolerated in both groups. We conclude that
L is an effective GH secretagogue in obese and nonobese young men and
may have therapeutic benefits when administered to relative (obese or
elderly) or absolute GH-deficient individuals.
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