Sustained growth hormone (GH) and insulin-like growth factor I responses to prolonged high-dose twice-daily GH-releasing hormone stimulation in middle-aged and older men.
Postulated mechanisms underlying the relative hyposomato-tropism of aging include reduced hypothalamic drive by GHRH. To test this notion, we administered 1 mg (n = 11) vs. 4 mg (n = 11) recombinant human GHRH-1,44-amide s.c. twice daily for 3 months in a double-blind, parallel-cohort design to 22 healthy men (ages, 53-68 yr). After 3 months, GHRH elevated: overnight GH concentrations from 0.71 +/- 0.19 to 1.74 +/- 0.39 microg/liter (P < 0.001; 1 mg) and from 0.80 +/- 0.15 to 5.12 +/- 0.40 microg/liter (P < 0.001; 4 mg) and IGF-I concentrations from 117 +/- 14 to 234 +/- 20 microg/liter (P = 0.007; 1 mg) and from 147 +/- 13 to 286 +/- 22 microg/liter (P < 0.001; 4 mg). Only the higher GHRH dose also increased total body water (tritium space; P = 0.024) and fat-free mass (dual-energy x-ray absorptiometry; P = 0.021), and reduced total abdominal adiposity (computed axial tomography scan; P = 0.042). Both supplementation schedules shortened the time required to walk 30 m and ascend four flights of stairs (P < 0.025 each). Lower extremity strength, aerobic capacity, and bone mineral density did not change. Local injection site reactions were common. We conclude that sc administration of a large dose of GHRH (4 mg) twice daily for 3 months elevates GH and IGF-I concentrations, increases total body water and fat-free mass, reduces total abdominal adiposity, and enhances certain performance measures in healthy aging men but causes local skin reactions.
Veldhuis
Johannes D
JD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Patrie
James T
JT
Frick
Kirsten
K
Weltman
Judith Y
JY
Weltman
Arthur
A
D000005:Abdomen; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001823:Body Composition / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012016:Reference Values; D012871:Skin Diseases / Q000139:chemically induced
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone