Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Authors

  • Bernard P. Halloran,

    Corresponding author
    1. Departments of Medicine and Physiology, University of California and Division of Endocrinology, Veterans Affairs Medical Center, San Francisco, California
    • Endocrine Unit VA Medical Center 4150 Clement St. (111N) San Francisco, CA 94121
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  • Daniel D. Bikle,

    1. Departments of Medicine and Physiology, University of California and Division of Endocrinology, Veterans Affairs Medical Center, San Francisco, California
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  • Jonathan Harris,

    1. Departments of Medicine and Physiology, University of California and Division of Endocrinology, Veterans Affairs Medical Center, San Francisco, California
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  • Christopher P. Autry,

    1. Departments of Medicine and Physiology, University of California and Division of Endocrinology, Veterans Affairs Medical Center, San Francisco, California
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  • Patricia A. Currier,

    1. National Aeronautics and Space Administration—Ames Research Center, Biomedical Research Division, Moffett Field, California
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  • Sharon Tanner,

    1. National Aeronautics and Space Administration—Ames Research Center, Biomedical Research Division, Moffett Field, California
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  • Patricia Patterson-Buckendahl,

    1. Biology Department, University of California, Santa Cruz, California
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  • Emily Morey-Holton

    1. National Aeronautics and Space Administration—Ames Research Center, Biomedical Research Division, Moffett Field, California
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Abstract

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 μg/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

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