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Thyroid Hormone and Skeletal Development
Cecilia H A Gouveia1, Manuela Miranda-Rodrigues2, Gisele M Martins3
1Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil; Experimental Pathophysiology Program, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
Insights
Thyroid hormone (TH) is vital for bone development and growth. This review explores how TH directly and indirectly impacts skeletal cells to regulate bone formation and maturation.
Area of Science:
- Endocrinology
- Skeletal Biology
- Developmental Biology
Background:
- Thyroid hormone (TH) plays a critical role in skeletal development from fetal life through puberty.
- TH influences both endochondral and intramembranous ossification, as well as longitudinal bone growth.
- TH acts directly on skeletal cells and indirectly via the growth hormone/insulin-like growth factor-1 axis.
Purpose of the Study:
- To review the mechanisms by which thyroid hormone regulates skeletal development.
- To highlight the direct and indirect actions of TH on bone growth and maturation.
Main Methods:
- Review of in vitro and in vivo studies.
- Analysis of mouse genetic studies.
- Examination of clinical data from patients with thyroid hormone resistance.
Main Results:
- Evidence supports direct actions of TH on skeletal cells.
- TH receptors, transporters, and enzymes are present in skeletal cells.
- Studies confirm the crucial role of TH in skeletal development.
Conclusions:
- Thyroid hormone is essential for normal skeletal development and maturation.
- Direct actions of TH in skeletal cells are critical for bone growth.
- Further understanding of TH's regulatory mechanisms in the skeleton is ongoing.
Abstract:
Thyroid hormone (TH) is essential for skeletal development from the late fetal life to the onset of puberty. During this large window of actions, TH has key roles in endochondral and intramembranous ossifications and in the longitudinal bone growth. There is evidence that TH acts directly in skeletal cells but also indirectly, specially via the growth hormone/insulin-like growth factor-1 axis, to control the linear skeletal growth and maturation. The presence of receptors, plasma membrane transporters, and activating and inactivating enzymes of TH in skeletal cells suggests that direct actions of TH in these cells are crucial for skeletal development, which has been confirmed by several in vitro and in vivo studies, including mouse genetic studies, and clinical studies in patients with resistance to thyroid hormone due to dominant-negative mutations in TH receptors. This review examines progress made on understanding the mechanisms by which TH regulates the skeletal development.
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