TY - JOUR
T1 - Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men
AU - Vittone, Janet
AU - Blackman, Marc R.
AU - Busby-Whitehead, Jan
AU - Tsiao, Chris
AU - Stewart, Kerry J.
AU - Tobin, Jordan
AU - Stevens, Tom
AU - Bellantoni, Michele F.
AU - Rogers, Marc A.
AU - Baumann, Gerhard
AU - Roth, Jesse
AU - Harman, S. Mitchell
AU - Spencer, Richard G.S.
N1 - Funding Information:
From the Departments of Medicine, Johns Hopkins Bayview Medical Center and Johns Hopkins University School of Medicine, Baltimore; the Gerontology Research Center, National Institute on Aging, National Institutes of Health (N1H), Baltimore; the Department of Kinesiology, University of Maryland, College Park, MD; and the Department of Medicine, Northwestern University School of Medicine, Chicago, IL. Submitted Aprii 23, 1996," accepted July 3, 1996. Supported in part by a grant from Ares-Serono Laboratories , General Clinical Research Center Grant No. MO-1-RR-O2719 from the National Center for Research Resources, NIH, and NIH Research Grant No. RO-1-AG-11002 (M.R.B.). Presented in part at the National Meeting of the American Federation for Clinical Research, Baltimore, MD, April 29, 1994. Address reprint requests to Marc R. Blackman, MD, Department of Medicine, Johns Hopkins Bayview Medical Center, or Richard G.S. Spencer, MD, PhD, Gerontology Research Center, Room 40-08, National Institute on Aging, National Institutes of Health, 4940 Eastern Ave, Baltimore, MD 21224. Copyright © 1997 by W.B. Saunders Company 0026-0495/97/4601-0017503.00/0
PY - 1997
Y1 - 1997
N2 - Age-related reductions in growth hormone (GH) and insulin-like growth factor-I (IGF-I) may contribute to decreased muscle mass and strength in older persons. The relationship of this phenomenon to skeletal muscle bioenergetics has not been reported. We sought to determine whether administration of GH-releasing hormone (GHRH) would sustain increases in GH and IGF-I and improve skeletal muscle function and selected measures of body composition and metabolism. We measured GH secretion, muscle strength, muscle histology, and muscle energy metabolism by phosphorus nuclear magnetic resonance spectroscopy (31P-NMRS), body composition, and endocrine- metabolic functions before and after 6 weeks of treatment. Eleven healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I levels were treated at home as outpatients by nightly subcutaneous self-injections of 2 mg GHRH for g weeks. We measured GH levels in blood samples obtained every 20 minutes from 8:00 PM to 8:00 AM; AM serum levels of IGF-I, IGF binding protein-3 (IGFBP-3), and GH binding protein (GHBP); muscle strength; muscle histology; the normalized phosphocreatine abundance, PCr/[PCr + Pi], and intracellular pH in forearm muscle by NMRS during both sustained and ramped exercise; body composition by dual-energy x-ray absorptiometry (DEXA); lipid levels; and glucose, insulin, and GH levels during an oral glucose tolerance test (OGTT). GHRH treatment increased mean nocturnal GH release (P < .02), the area under the GH peak ([AUPGH] P < .006), and GH peak amplitude (P < .05), with no change in GH pulse frequency or in levels of IGF-I, IGFBP- 3, or GHBP. Two of six measures of muscle strength, upright row (P < .02) and shoulder press (P < .04), and a test of muscle endurance, abdominal crunch (P < .03), improved. GHRH treatment did not alter exercise-mediated changes in PCr/[PCr + Pi] or intracellular pH, but decreased or abolished significant relationships between changes in PCr/[PCr + Pi] or pH and indices of muscle strength. GHRH treatment did not change weight, body mass index, waist to hip ratio, DEXA measures of muscle and fat, muscle histology, glucose, insulin, or GH responses to OGTT, or lipids. No significant adverse effects were observed. These data suggest that single nightly doses of GHRH are less effective than multiple daily doses of GHRH in eliciting GH- and/or IGF-I- mediated effects. GHRH treatment may increase muscle strength, and it alters baseline relationships between muscle strength and muscle bioenergetics in a manner consistent with a reduced need for anaerobic metabolism during exercise. Thus, an optimized regimen of GHRH administration might attenuate some of the effects of aging on skeletal muscle function in older persons.
AB - Age-related reductions in growth hormone (GH) and insulin-like growth factor-I (IGF-I) may contribute to decreased muscle mass and strength in older persons. The relationship of this phenomenon to skeletal muscle bioenergetics has not been reported. We sought to determine whether administration of GH-releasing hormone (GHRH) would sustain increases in GH and IGF-I and improve skeletal muscle function and selected measures of body composition and metabolism. We measured GH secretion, muscle strength, muscle histology, and muscle energy metabolism by phosphorus nuclear magnetic resonance spectroscopy (31P-NMRS), body composition, and endocrine- metabolic functions before and after 6 weeks of treatment. Eleven healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I levels were treated at home as outpatients by nightly subcutaneous self-injections of 2 mg GHRH for g weeks. We measured GH levels in blood samples obtained every 20 minutes from 8:00 PM to 8:00 AM; AM serum levels of IGF-I, IGF binding protein-3 (IGFBP-3), and GH binding protein (GHBP); muscle strength; muscle histology; the normalized phosphocreatine abundance, PCr/[PCr + Pi], and intracellular pH in forearm muscle by NMRS during both sustained and ramped exercise; body composition by dual-energy x-ray absorptiometry (DEXA); lipid levels; and glucose, insulin, and GH levels during an oral glucose tolerance test (OGTT). GHRH treatment increased mean nocturnal GH release (P < .02), the area under the GH peak ([AUPGH] P < .006), and GH peak amplitude (P < .05), with no change in GH pulse frequency or in levels of IGF-I, IGFBP- 3, or GHBP. Two of six measures of muscle strength, upright row (P < .02) and shoulder press (P < .04), and a test of muscle endurance, abdominal crunch (P < .03), improved. GHRH treatment did not alter exercise-mediated changes in PCr/[PCr + Pi] or intracellular pH, but decreased or abolished significant relationships between changes in PCr/[PCr + Pi] or pH and indices of muscle strength. GHRH treatment did not change weight, body mass index, waist to hip ratio, DEXA measures of muscle and fat, muscle histology, glucose, insulin, or GH responses to OGTT, or lipids. No significant adverse effects were observed. These data suggest that single nightly doses of GHRH are less effective than multiple daily doses of GHRH in eliciting GH- and/or IGF-I- mediated effects. GHRH treatment may increase muscle strength, and it alters baseline relationships between muscle strength and muscle bioenergetics in a manner consistent with a reduced need for anaerobic metabolism during exercise. Thus, an optimized regimen of GHRH administration might attenuate some of the effects of aging on skeletal muscle function in older persons.
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U2 - 10.1016/S0026-0495(97)90174-8
DO - 10.1016/S0026-0495(97)90174-8
M3 - Article
C2 - 9005976
AN - SCOPUS:0008077420
SN - 0026-0495
VL - 46
SP - 89
EP - 96
JO - Metabolism: clinical and experimental
JF - Metabolism: clinical and experimental
IS - 1
ER -