State the main function of TSH
Answers
Thyroid-stimulating hormone, also known as TSH, is a glycoprotein hormone produced by the anterior pituitary. It is the primary stimulus for thyroid hormone production by the thyroid gland. It also exerts growth effects on thyroid follicular cells leading to enlargement of the thyroid. The hypothalamic-pituitary axis regulates TSH release. Specifically, neurons in the hypothalamus release TRH, or thyroid-releasing hormone, which stimulates thyrotrophs of the anterior pituitary to secrete TSH. TSH, in turn, stimulates thyroid follicular cells to release thyroid hormones in the form of T3 or T4. Triiodothyronine, or T3, is the active form of thyroid hormone. Though it represents only 20% of the released hormone, the majority of T3 comes from the peripheral conversion of T4 to T3. Tetraiodothyronine, also known as thyroxine or T4, constitutes more than 80% of the secreted hormone. When released into the circulation, it forms T3 through the process of de-iodination. T4 and T3 can then exert negative feedback on the anterior pituitary with high levels of T3/T4 decreasing TSH secretion and low levels of T3/T4 increasing TSH release. In this review, we discuss the physiology, biochemistry, and clinical relevance of TSH.
TSH binds to and activates the TSH receptor (TSHR), which is a G-protein coupled receptor (GPCR) on the basolateral surface of thyroid follicular cells. TSHR is coupled to both Gs and Gq G-proteins, activating both the cAMP pathway (via Gsa) and the phosphoinositol/calcium (IP/Ca2+; via Gq) second messenger signaling cascades. The Gs pathway activates iodide uptake, thyroid hormone secretion, and gland growth and differentiation. The Gq pathway is rate-limiting for hormone synthesis by stimulating iodide organification. A gain in function mutation of the TSH receptor results in hyperthyroidism, while a loss in function mutation results in hypothyroidism.
Understanding the role of TSH in stimulating T3 and T4 secretion requires knowledge of the thyroid hormone synthesis pathway. The two main components of T3 and T4 are iodine and tyrosine. Iodine (I2) forms through oxidation of iodide (I-) after thyroid follicular cells actively take up iodide (I-) from the bloodstream against its concentration gradient. Tyrosine, on the other hand, comes from thyroglobulin, a tyrosine-rich protein synthesized by thyroid follicular cells. Following iodide uptake and oxidation, iodine binds tyrosine residues on thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Triiodothyronine, or T3, forms when an MIT mixes up with DIT. Likewise, the coupling of two DITs creates tetraiodothyronine (T4), or thyroxine. The process of iodide oxidation, thyroglobulin iodination, and MIT and DIT coupling is catalyzed by an enzyme called, thyroperoxidase. TSH stimulates thyroid hormone secretion through enhancing iodide uptake, thyroglobulin synthesis, and thyroperoxidase activity. Additionally, TSH also increases blood flow to the thyroid gland and stimulates hypertrophy and hyperplasia of thyroid follicular cells to exert growth effects on the thyroid gland.