Thyrotropin Structure Function and Importance in Endocrinology

Thyrotropin, also known as thyroid stimulating hormone (TSH hormone full form) are the substances that are produced in the cell known as thyrotropes and are located in the anterior pituitary gland. The structure of the thyrotropin-releasing hormone is given below.

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This thyrotropic hormone gland is located at the base of the brain and these hormones stimulate the signals from the hypothalamus gland in the brain. Thyrotropin or thyroid stimulating hormone is basically a pituitary hormone that promotes the growth of the thyroid gland so that it can stimulate the synthesis of thyroid hormones that includes thyroxine (T4) and triiodothyronine (T3) in the gland. Thyrotropin or TSH secreted by the pituitary gland also acts as thyroprotein hormones that are secreted by thyrotropic cells also present in the pituitary gland of the human body. It regulates the endocrine function of the thyroid. When there is excess thyroid stimulating hormone produced in the body by thyroprotein, the excess thyroid stimulating hormone travels all the way to the receptors of the pituitary gland that slow down the secretion of thyroprotein and hence TSH. This negative feedback from the excess thyroid stimulating hormone to the pituitary gland helps maintain a proper level of TSH in the body. The functioning of thyroprotein in the thyroid gland is described by the given diagram.

TSH Function and Production

The thyroprotein function or TSH function to regulate the metabolism in the body is done as it binds itself to the specific receptors present on the surface of the cell of the thyroid gland. This binding of THS to the stimulator results in the breakdown of thyroglobulin. Now thyroglobulin is basically the large protein whose cleavage results in the formation of thyroid hormones that are stored in the follicles of the thyroid gland. This in turn results in the secretion of thyroxine and triiodothyronine in circulation. Thyroprotine commonly uses the iodine present in the blood for the formation of two major functioning hormones,  thyroxine (T4) and triiodothyronine (T3) that promotes metabolism at almost all the tissues of the body. Thus the major thyroid stimulating hormone functions are-

1. They affect body weight as they regulate the rate at which the body will burn its calories by stimulating the synthesis and breakdown of proteins and carbohydrates.

2. They influence the rate at which the food will move into the digestive tract.

3. It stimulates the heart rate by stimulating the contractions in the heart as it controls the movement and contraction of the muscles present throughout the body.

4. It keeps the heart healthy by degrading the cholesterol and triglyceride that accumulates around the organ.

5. It can raise or lower the body temperature.

6. It enhances the vitamin requirement in the body and also stimulates adrenergic receptors to catecholamines. 

Thus when the serum thyrotropin concentration becomes high in the body, there is low negative feedback inhibition by thyrotropin to the receptors of the pituitary gland to secret less TSH and hence the patience suffers from hypothyroidism due to deficiency of thyroid in the body. Alternatively, when the serum thyrotropin concentration becomes less in the body, there is a hike in negative feedback inhibition by thyrotropin to the receptors of the pituitary gland to secret more TSH and hence the patient suffers from hyperthyroidism due to deficiency of thyroid in the body. Thus the measurement of thyrotropin serum concentration in the body is necessary in order to identify if any hypo or hyperthyroidism situation arises in the body.  Thyroid stimulating hormone function pictorial representation is given below.

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Physiology of THS

1. Hormone levels: THS functions with about one hour of half-life in order to initiate the thyroid gland to release thyroxine (T4)  which does not regulate the metabolism system of the body largely but is converted to triiodothyronine (T3) which is actually the active hormone that initiates the metabolism system in the body. Most of this conversion takes place in the liver (about 80%) and the remaining small amount of it takes place in the thyroid gland itself (about 20%). The thyroid hormones are released in the body throughout life but reach their peak during growth and development and under stress. Hypothalamus is the baseline of the human brain that releases thyrotropin-releasing hormone (TRH) that in turn stimulates the pituitary gland to release TSH. Another substance called somatostatin in the hypothalamus has the opposite effect on the pituitary gland as it inhibits or decreases the production of TSH in the anterior pituitary. The concentration of thyroxine (T4) and triiodothyronine (T3) together as thyroid hormone in the blood cell regulates the release of TSH if the thyroid hormone concentration increases in the blood TSH decreases and vice versa. The entire hormone functioning is shown in the diagram below.

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2. Subunits: TSH is also known as glycoprotein and it consists of two subunits, namely, alpha and beta subunits. the alpha subunit which is also known as the chorionic gonadotropin subunit is quite identical to follicle-stimulating hormone(FSH), human chorionic gonadotropin (HCG), and luteinizing hormone (LH). This alpha subunit being the effector region is responsible for stimulating adenylate cyclase that is involved in the generation of cAMP. The alpha subunit chain is made up of 92 sequences of amino acids. On the other hand, the beta subunit chain is made up of 118 amino acid sequences and is unique to TSH, therefore determining the specificity of the receptor for the hormone.

3. The TSH Receptors: TSH receptor is mainly located in the thyroid follicular cells. The stimulation in these receptors increases the T3 and T4 hormone production and release from the pituitary gland. This stimulation of the TSH stimulators occurs in six steps for the synthesis of thyroid hormones. 

1. By increasing the intracellular concentration of iodine by regulating up the sodium-iodide symporter present on the basolateral membrane of the thyroid follicular cell.

2. Stimulating iodine concentration of the thyroglobulin which is a precursor protein of the thyroid hormone and present in the follicular lumen.

3. Stimulating the iodinated tyrosine residue conjugates. This results in the synthesis of T3 and T4 hormone that stays attached to the thyroglobulin protein.

4. Increased endocytosis of the iodinated thyroglobulin protein that is present in the apical membrane situated at the back of the follicular cell.

5. Proteolysis of thyroglobulin protein is stimulated to form free T3 and T4 hormones individually.

6. With the help of an unknown mechanism, T3 and T4 hormones present across the basolateral membrane enter into the blood cell for circulation.

Applications of THS

1. Diagnostic: TSH range may vary slightly depending on the method of analysis but the cut-off for diagnosing the dysfunctioning of the thyroid may not always equate. Thus the reference range selected by the Association for Clinical Biochemistry in the United Kingdoms is 0.4 - 4.0 μlU/mL or 0.4 -4.0 mlU/L. TSH concentration is at a higher level in infants and reduces gradually as they grow up.  According to NACB recommended range of TSH for infants is 1.3 - 19 μlU/mL at the time of birth that gradually drops down to 0.6 - 10 μlU/mL at 10 weeks of age and further drops to 0.4 - 7.0 μlU/mL at 14 months. As the child attains puberty to adulthood the range of TSH levels in the body becomes 0.3 - 3.0 μlU/mL.

2. Diagnosis of Diseases: TSH concentrations are usually measured clinically in order to identify if the human body is experiencing hyperthyroidism or hypothyroidism. For clinical assessment concentration of TSH and T4 is the most important factor, though in some cases T3 concentration can also be considered.

Source of Pathology and Disease-Causing Condition

3. Monitoring: the therapeutic range for the monitoring of TSH levels in the patients is set between 0.3 - 3.0 μlU/mL. For the hypothyroid patients who are on thyroxine, the concentration of TSH in the body alone is sufficient for monitoring. However, the increase in the TSH concentration in the body is considered to be poor compliance with the body or indicates under-replacement. For hyperthyroid patience, both TSH and thyroxine hormone levels need to be taken into consideration. It has been observed in various studies that TSH distribution increases progressively as age increases.