Mechanisms of action of thyroid hormones in the skeleton.
BACKGROUND
Thyroid hormones regulate skeletal development, acquisition of peak bone mass and adult bone maintenance. Abnormal thyroid status during childhood disrupts bone maturation and linear growth, while in adulthood it results in altered bone remodeling and an increased risk of fracture


METHODS
This review considers the cellular effects and molecular mechanisms of thyroid hormone action in the skeleton. Human clinical and population data are discussed in relation to the skeletal phenotypes of a series of genetically modified mouse models of disrupted thyroid hormone signaling.


CONCLUSIONS
Euthyroid status is essential for normal bone development and maintenance. Major thyroid hormone actions in skeletal cells are mediated by thyroid hormone receptor α (TRα) and result in anabolic responses during growth and development but catabolic effects in adulthood. These homeostatic responses to thyroid hormone are locally regulated in individual skeletal cell types by the relative activities of the type 2 and 3 iodothyronine deiodinases, which control the supply of the active thyroid hormone 3,5,3'-L-triiodothyronine (T3) to its receptor.


CONCLUSIONS
Population studies indicate that both thyroid hormone deficiency and excess are associated with an increased risk of fracture. Understanding the cellular and molecular basis of T3 action in skeletal cells will lead to the identification of new targets to regulate bone turnover and mineralization in the prevention and treatment of osteoporosis. This article is part of a Special Issue entitled Thyroid hormone signaling.
The Medical Centre of Postgraduate Education, Department of Biochemistry and Molecular Biology, ul.Marymoncka 99/103, 01-813 Warsaw, Poland.
Anna
A
Wojcicka
J H Duncan
JH
Bassett
Graham R
GR
Williams
D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones