What is Thyrotropin?
Thyrotropin is also known as thyroid-stimulating hormone (TSH) or thyrotropic hormone. The thyrotropic cells of the adenohypophysis secrete Thyrotropin. It is a glycoprotein hormone that regulates the endocrine activity of the thyroid gland.
It binds to specific receptors on the surface of the thyroid glands, which leads to the cleavage of thyroglobulin (a large protein stored in the follicles within the thyroid gland) and produces Thyroxine T4 (Tetraiodothyronine) and Triiodothyronine (T3). These two hormones regulate the metabolism in almost every tissue present in the body.
Moreover, thyrotropin affects the synthesis of thyroglobulin and the growth of thyroid cells. The paraventricular cells of the hypothalamus secrete Thyrotropin-releasing hormone (TRH). TRH then commands the release of the thyrotropin hormone. This release forms a hypothalamic pituitary thyroid axis in which the regulation of the secretion of hormones occurs through a feedback mechanism. Whenever there is excess thyroxine in the circulation, this acts on the specific receptors of the pituitary. This action suppresses the level of thyrotropin and, ultimately, Thyrotropin-Releasing Hormone.
When there is insufficient thyroxine in the circulation, the positive feedback from elevated thyrotropin levels stimulates the release of further thyroxine. In this way, the feedback mechanism maintains the levels of thyroxine in the circulation corresponding to the metabolic requirement of the body.
The average concentration of Thyrotropin in serum ranges from 0.4 to 4.2 mU/L. Its levels are naturally elevated in primary hypothyroidism and suppressed in thyrotoxicosis. The half-life of Thyrotrophin in the plasma is only 30 minutes. The circulating levels of thyrotropin manifest circadian and pulsatile variation.
The human body secrets Thyrotropin at a rate of 40-150 mU/L per day. The secretion of Thyrotropin continues throughout life. However, its concentration is exceptionally high during rapid growth and development and periods of increased metabolic demand such as surgery. Another hormone released by the hypothalamus called Somatostatin antagonizes the action of Thyrotropin. The molecular weight of thyrotropin is 28000 Da.
Mechanism of Action
Thyrotropin is a glycoprotein and consists of Alpha and beta subunits. The alpha subunit is similar to other glycoprotein hormones such as Luteinizing hormone (LH), Follicle Stimulating Hormone (FSH), and Human Chorionic Gonadotropin (HCG). Conversely, the beta chain is different in these glycoproteins and imparts their specific biological properties. These glycoproteins function through Cyclic Adenosine Monophosphate (cAMP) signaling second messenger system. The dual messenger system converts Adenosine monophosphate into Cyclic adenosine monophosphate.
However, thyrotropin activates another signaling cascade; specifically, it is called Inositol Triphosphate second messenger system (IP3). Thyrotropin activates specific G protein-coupled receptors on the surface of thyroid follicular cells. It leads to the activation of both cAMP and IP3 /Ca+2 pathways. This activation ultimately enhances iodine uptake in the follicular thyroid cells. An array of further steps leads to the formation of T4 and T3, which are responsible for all the downstream physiological effects of the thyroid hormone.
Clinical Implications of Thyrotropin
Thyrotropin affects the body by producing thyroxine and triiodothyronine. Below are the effects produced by them:
1. Regulation of metabolism: Thyrotropin peptide stimulates the secretion of Thyroxine T4 and Triiodothyronine T3 by the thyroid gland. This hormone activates various metabolic processes, including increased glucose absorption, gluconeogenesis, glycogenolysis, lipolysis, and synthesis/degradation of the protein.
All of these phenomena lead to a net state of catabolism.
● The thyroid hormone regulates the rate at which the body burns calories. Therefore, the thyroid hormone level can affect weight gain and weight loss in the body.
● The thyroid hormone helps the body maintain its temperature.
● It regulates the rate of the regeneration process of several tissues in the body.
● It affects the speed at which the food moves through the gut.
● It controls muscle contraction.
2. Role of Thyrotropin as a Screening Test: It is the first-line screening test in diagnosing both the state of hypothyroidism and hyperthyroidism in the body. Measuring the thyrotropin level is considered a better method than measuring direct levels of T3 and T4. This consideration is because of two reasons. First, the thyrotropin levels are affected before the change in the T3 and T4 groups in any pathological state. Secondly, it is more reliable than T3 and T4 levels because T3 and T4 keep fluctuating.
3. A Tool for Monitoring Treated Patients with Thyroid Cancer: Researchers use recombinant thyrotropin as an adjunct diagnostic method to monitor the recurrence in the treated patients of well-differentiated thyroid carcinoma.
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