Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats
T Kuber Sampath1, Petra Simic, Rebecca Sendak
1Genzyme Corporation, Framingham, Massachusetts 01701-9322, USA. kuber.sampath@genzyme.com
Summary
Systemic administration of low-dose thyroid-stimulating hormone (TSH) effectively increased bone volume and strength in aged ovariectomized rats. TSH demonstrated both bone-sparing and bone-building effects by influencing osteoclast and osteoblast activity.
Area of Science:
- Endocrinology
- Bone Biology
- Pharmacology
Background:
- Thyroid-stimulating hormone (TSH) receptor haploinsufficiency is linked to reduced bone mass.
- TSH may directly influence bone remodeling independent of thyroid hormone levels.
Purpose of the Study:
- To investigate the effects of systemic TSH administration on bone mass in aged ovariectomized (OVX) rats.
- To determine TSH's in vitro impact on osteoclast and osteoblast differentiation.
Main Methods:
- Aged OVX rats received TSH therapy in prevention or restoration modes.
- Bone mineral density, microarchitecture, and mechanical strength were assessed.
- In vitro studies examined TSH effects on osteoclast and osteoblast progenitor cells.
Main Results:
- Low-dose TSH prevented bone loss and restored bone mass in OVX rats without altering T3/T4 levels.
- TSH increased bone mineral density, trabecular and cortical bone volume, and bone formation rates.
- In vitro, TSH inhibited RANKL-induced osteoclast formation and stimulated osteoblast differentiation.
Conclusions:
- Systemically administered TSH effectively prevents and restores bone mass in aged OVX rats.
- TSH exerts both antiresorptive and anabolic effects on bone remodeling.
- TSH directly impacts bone cells, suggesting a therapeutic potential for osteoporosis.
Related Concept Videos
01:29Bone Disorders
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
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...
01:17Hormones 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...
01:23Hypothyroidism 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...
01:20Synthesis and Regulation of Thyroid Hormones
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
01:40Bone Remodeling
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.