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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

Division of Endocrinology and Metabolism, Department of Internal Medicine (J.D.V.), Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905; and Departments of Health Evaluation Sciences (J.T.P.), Medicine (J.Y.W., A.W.), and Human Services (A.W.), General Clinical Research Center, School of Medicine (K.F.), University of Virginia Health System, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, 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. E-mail: veldhuis.johannes{at}mayo.edu.

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 sc 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 µg/liter (P < 0.001; 1 mg) and from 0.80 ± 0.15 to 5.12 ± 0.40 µg/liter (P < 0.001; 4 mg) and IGF-I concentrations from 117 ± 14 to 234 ± 20 µg/liter (P = 0.007; 1 mg) and from 147 ± 13 to 286 ± 22 µg/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.

This article has been cited by other articles:

				J. D Veldhuis, J. M Patrie, K. Frick, J. Y Weltman, and A. L Weltman Administration of recombinant human GHRH-1,44-amide for 3 months reduces abdominal visceral fat mass and increases physical performance measures in postmenopausal women Eur. J. Endocrinol., November 1, 2005; 153(5): 669 - 677. [Abstract] [Full Text] [PDF]