Related Experiment Videos
Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism
J H Duncan Bassett1, Patrick J O'Shea, Srividya Sriskantharajah
1Molecular Endocrinology Group, Division of Medicine and Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
Molecular Endocrinology (Baltimore, Md.)
|March 1, 2007
Summary
Thyroid hormone receptor alpha (TRalpha) plays a key role in bone health. TRalpha mediates bone loss in thyrotoxicosis, independent of TSH, offering a new target for osteoporosis treatment.
Area of Science:
- Endocrinology
- Bone Biology
- Molecular Medicine
Background:
- Thyrotoxicosis is an under-recognized cause of osteoporosis.
- The precise molecular mechanisms underlying thyroid disease-induced bone loss are not fully understood.
- Recent hypotheses suggest TSH deficiency, not thyroid hormone excess, may drive osteoporosis.
Purpose of the Study:
- To investigate the molecular mechanisms of osteoporosis in thyroid disease.
- To characterize the skeletal phenotypes of mice lacking thyroid hormone receptor alpha (TRalpha) or beta (TRbeta).
- To determine the role of TRalpha and TRbeta in mediating the skeletal effects of thyroid hormones.
Main Methods:
- Generated and analyzed mice models deficient in TRalpha (TRalpha(0/0)) and TRbeta (TRbeta-/-).
- Assessed skeletal parameters including bone mineral density, osteoclast activity, and endochondral ossification.
- Analyzed thyroid hormone and TSH levels, alongside T3 target gene expression in the skeleton.
Main Results:
- Adult TRalpha(0/0) mice exhibited osteosclerosis with reduced osteoclastic bone resorption, indicating skeletal hypothyroidism.
- Adult TRbeta-/- mice showed osteoporosis with increased bone resorption, indicating skeletal thyrotoxicosis.
- Juvenile TRalpha(0/0) mice displayed delayed ossification, while TRbeta-/- mice showed advanced ossification.
Conclusions:
- Bone loss in thyrotoxicosis is mediated predominantly by TRalpha, independent of circulating TSH levels.
- TRalpha is identified as a novel therapeutic target for preventing and treating osteoporosis.
- Understanding receptor-specific effects of thyroid hormones is crucial for managing bone metabolic disorders.
Related Concept Videos
01:25Hyperthyroidism I: Introduction
Hyperthyroidism is a type of thyrotoxicosis characterized by the thyroid gland's overproduction of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). This hormone excess increases the basal metabolic rate and enhances sensitivity to catecholamines.DiagnosisDiagnosis is based on clinical features and biochemical testing. It typically shows suppressed thyroid-stimulating hormone (TSH) levels below 0.4 mIU/L, with elevated free T3 and/or T4. Additional tests, including thyroid...
01:27Hyperthyroidism II: Pathophysiology
Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
01:17Hormones and Bone Tissue
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:24Graves Disease II: Pathophysiology
Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...
01:18Functions of Thyroid Hormones
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
01:23Hypothyroidism II: Pathophysiology
Hypothyroidism is a disorder characterized by insufficient production of thyroid hormones, which regulate metabolism, energy balance, and multiple organ systems.TypesHypothyroidism is classified based on the level of dysfunction. Primary hypothyroidism results from intrinsic thyroid gland dysfunction, causing reduced hormone production despite normal or increased stimulation. Secondary hypothyroidism arises from inadequate thyroid-stimulating hormone (TSH) secretion by the pituitary. Tertiary...