Abstract
The osteoporosis associated with human hyperthyroidism has traditionally been attributed to elevated thyroid hormone levels. There is evidence, however, that thyroid-stimulating hormone (TSH), which is low in most hyperthyroid states, directly affects the skeleton. Importantly, Tshr-knockout mice are osteopenic. In order to determine whether low TSH levels contribute to bone loss in hyperthyroidism, we compared the skeletal phenotypes of wild-type and Tshr-knockout mice that were rendered hyperthyroid. We found that hyperthyroid mice lacking TSHR had greater bone loss and resorption than hyperthyroid wild-type mice, thereby demonstrating that the absence of TSH signaling contributes to bone loss. Further, we identified a TSH-like factor that may confer osteoprotection. These studies suggest that therapeutic suppression of TSH to very low levels may contribute to bone loss in people.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Bone Density
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Bone Diseases, Metabolic / genetics
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Bone Resorption / blood
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Bone Resorption / physiopathology
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Dose-Response Relationship, Drug
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Drug Implants
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Hormone Replacement Therapy
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Hyperthyroidism / blood
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Hyperthyroidism / complications*
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Hyperthyroidism / drug therapy
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Hypothyroidism / blood
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Hypothyroidism / chemically induced
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Methimazole / toxicity
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Osteoporosis / blood
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Osteoporosis / etiology*
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Osteoporosis / physiopathology
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Phenotype
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Receptors, Thyrotropin / deficiency*
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Receptors, Thyrotropin / genetics
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Signal Transduction
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Thyrotropin / blood
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Thyrotropin / deficiency
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Thyrotropin / physiology*
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Thyroxine / administration & dosage
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Thyroxine / therapeutic use
Substances
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Drug Implants
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Receptors, Thyrotropin
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Methimazole
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Thyrotropin
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Thyroxine