Thyroid Stimulating Hormone (TSH, Thyrotropin)

THYROID STIMULATING HORMONE (TSH, THYROTROPIN)

It is a 210 amino acid, two chain glycoprotein (22% sugar), MW 30000.

Physiological Function

TSH stimulates thyroid to synthesize and secrete thyroxine (T₄) and triiodothyronine (T₃). Its actions are:

·   Induces hyperplasia and hypertrophy of thyroid follicles and increases blood supply to the gland.

·       Promotes trapping of iodide by thyroid.

· Promotes organification of trapped iodine and its incorporation into T₃ and T₄ by increasing peroxidase activity.

·  Enhances endocytotic uptake of thyroid colloid by the follicular cells and proteolysis of thyroglobulin to release more of T₃ and T₄. This action starts within minutes of TSH administration.

The TSH receptor present on thyroid cells is a G protein coupled receptor which utilizes the adenylyl cyclase cAMP transducer mechanism to produce its effects. In human thyroid cells high concentration of TSH also induces PIP₂ hydrolysis. The resulting increase in cytosolic Ca2+ and protein kinase C activation may also mediate TSH actions.

Regulation Of Secretion

Synthesis and release of TSH by pituitary is controlled by hypothalamus through TRH. The negative feed back inhibiting TSH secretion is provided by the thyroid hormones which act primarily at the level of the pituitary, but also in the hypothalamus. T₃ has been shown to reduce TRH receptors on thyrotropes.

Pathological Involvement

Only few cases of hypo or hyperthyroidism are due to inappropriate TSH secretion. In majority of cases of myxoedema TSH levels are markedly elevated because of deficient feedback inhibition. Graves’ disease is due to an immunoglobulin of the IgG class which attaches to the thyroid cells and stimulates them in the same way as TSH. Consequently, TSH levels are low. Contrary to earlier belief, TSH is not responsible for exophthalmos seen in Graves’ disease because TSH levels are low.

Use

Thyrotropin has no therapeutic use. Thyroxine is the drug of choice even when hypothyroidism is due to TSH deficiency. The diagnostic application is to differentiate myxoedema due to pituitary dysfunction from primary thyroid disease.