The hypothalamus secretes
thyrotrophin releasing hormone (TRH), a tripeptide, which stimulates
the production of thyroid stimulating hormone (TSH) from the anterior
TSH increases the production and release of thyroxine (T4) and triiodothyronine (T3) from the thyroid gland in the neck. T4 and T3 reduce the production of TSH, providing a negative feedback mechanism for regulating the amount of thyroid hormones produced. The thyroid produces mainly T4, some of which is converted to T3 in the blood or in other tissues. Most of the thyroid hormones are protein-bound, but it is the unbound fraction is active. The thyroid hormones increase cell metabolism and are vital to normal growth and development. They also enhance the effects of circulating catecholamines
Excessive thyroid hormone production (thyrotoxicosis) is characterised by a variety of symptoms which may include weight loss, increased appetite, diarrhoea, tremor, irritability, intolerance of hot weather, increased sweating, palpitations and generalised itching. Diagnosis requires estimation of thyroid hormone levels and thyroid gland scanning. Treatment options consist of drugs to suppress thyroid gland activity, surgical removal of part of the thyroid gland or radioactive iodine.
Reduced thyroid hormone production (myxoedema or hypothyroidism) characteristically has an insidious onset. Symptoms may include weight gain, constipation, dislike of cold weather, hoarse voice, lethargy, depression and dementia. Diagnosis requires estimation of thyroid hormone levels. Treatment is with thyroxine supplementation.
Molecular studies of thyroid hormone action have resulted in the identification of two novel functionally distinct thyroid hormone receptor variants in the rat that are variably expressed in a tissue specific and hormone regulated manner. The identification of these new variants suggests a novel mechanism that modulates how individual tissues may independently respond to thyroid hormones. We have also recently identified a novel receptor variant mRNA in man which will enable us investigate how thyroid hormone action is regulated in human health and disease. This may lead to the provision of new methods for the assessment of tissue thyroid status in common clinical conditions that result in the poorly understood "sick euthyroid syndrome".
Studies of thyroid hormone action in bone and developing cartilage are designed to determine how T3 influences normal bone turnover and longitudinal growth and will ultimately provide new markers of bone cell activity to aid the management of patients with osteoporosis and growth disorders. Initial studies have shown that thyroid hormone regulates the pace of chondrocyte differentiation during endochondral bone formation by interfering with the expression of PTHrP in the epiphyseal growth plate. PTHrP is a key component of a negative feedback loop in cartilage that controls long bone development and growth. In bone cells we have identified the FGF receptor as a target gene for thyroid hormone indicating that crosstalk between growth factor and thyroid hormone signaling may be a hitherto unknown, but key, pathway that regulates bone mass.