Document Detail

Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice.
MedLine Citation:
PMID:  22513648     Owner:  NLM     Status:  MEDLINE    
Understanding how bone growth is regulated by hormonal and mechanical factors during early growth periods is important for optimizing the attainment of peak bone mass to prevent or postpone the occurrence of fragility fractures later in life. Using genetic mouse models that are deficient in thyroid hormone (TH) (Tshr(-/-) and Duox2(-/-)), growth hormone (GH) (Ghrhr(lit/lit)), or both (Tshr(-/-); Ghrhr(lit/lit)), we demonstrate that there is an important period prior to puberty when the effects of GH are surprisingly small and TH plays a critical role in the regulation of skeletal growth. Daily administration of T3/T4 during days 5 to 14, the time when serum levels of T3 increase rapidly in mice, rescued the skeletal deficit in TH-deficient mice but not in mice lacking both TH and GH. However, treatment of double-mutant mice with both GH and T3/T4 rescued the bone density deficit. Increased body fat in the TH-deficient as well as TH/GH double-mutant mice was rescued by T3/T4 treatment during days 5 to 14. In vitro studies in osteoblasts revealed that T3 in the presence of TH receptor (TR) α1 bound to a TH response element in intron 1 of the IGF-I gene to stimulate transcription. In vivo studies using TRα and TRβ knockout mice revealed evidence for differential regulation of insulin-like growth factor (IGF)-I expression by the two receptors. Furthermore, blockade of IGF-I action partially inhibited the biological effects of TH, thus suggesting that both IGF-I-dependent and IGF-I-independent mechanisms contribute to TH effects on prepubertal bone acquisition.
Weirong Xing; Kristen E Govoni; Leah Rae Donahue; Chandrasekhar Kesavan; Jon Wergedal; Carlin Long; J H Duncan Bassett; Apostolos Gogakos; Anna Wojcicka; Graham R Williams; Subburaman Mohan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  27     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-19     Completed Date:  2012-09-27     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1067-79     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 American Society for Bone and Mineral Research.
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MeSH Terms
Bone Development / genetics*
Cells, Cultured
Disease Models, Animal
Gene Expression Regulation, Developmental* / drug effects
Insulin-Like Growth Factor I / genetics*,  metabolism*
Mice, Inbred C57BL
Mice, Knockout
Osteoblasts / drug effects
Polymerase Chain Reaction
Puberty / physiology*
Thyroid Hormones / genetics,  metabolism*,  pharmacology
Grant Support
AR 048139/AR/NIAMS NIH HHS; G0501486//Medical Research Council; G0800261//Medical Research Council; G0800359//Medical Research Council; R01 AR048139/AR/NIAMS NIH HHS; R01 AR048139-04/AR/NIAMS NIH HHS
Reg. No./Substance:
0/Thyroid Hormones; 67763-96-6/Insulin-Like Growth Factor I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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