The Thyroid Gland

INTRODUCTION

The Thyroid gland is a butterfly-shaped gland located just inferior to the larynx (voice box). It is composed of the right and left lateral lobes, one on either side of the trachea, that are connected by an isthmus. The normal mass of the thyroid is about 30g. It is highly vascularized and receives 80-120mL of blood per minute.

Microscopic spherical sacs called thyroid follicles are the structural units of the thyroid gland. The wall of each follicle consists of primarily of cells called follicular cells. A basement membrane surrounds each follicle. When the follicular cells are inactive, their shape is low cuboidal to squamous, but under the influence of TSH (Thyroid-stimulating hormone), they become active in secretion and range from cuboidal to low columnar in shape.

The follicular cells produce two hormones: Thyroxine, which is also called tetraiodothyronine or T4 because it contains four atoms of iodine, and triiodothyronine or T3, which contains three atoms of iodine. T3 and T4 together are also known as thyroid hormones.

Few cells called parafollicular cells or C cells lie between follicles. They produce the hormone calcitonin, which helps regulate calcium homeostasis.

FORMATION, STORAGE, AND RELEASE OF THYROID HORMONE

1.    Iodide Trapping:

Thyroid follicular cells trap iodide ions (I) by actively transporting them from the blood into the cytosol. As a result, the thyroid gland normally contains most of the iodide in the body.

2.    Synthesis of thyroglobulin:

While the follicular cells are trapping Iodine (I), they are also synthesizing thyroglobulin (TGB), a large glycoprotein that is produced in the rough endoplasmic reticulum, modified in the Golgi complex, and packaged into secretory vesicles. The vesicles then undergo exocytosis, which releases TGB into the lumen of the follicle.

3.    Oxidation of iodide:

Some of the amino acids in TGB are tyrosines that will become iodinated. However, negatively charged iodide ions can’t bind to tyrosine until they undergo oxidation (removal of electrons) to iodine: 2I- → I2. As the iodide ions are being oxidized, they pass through the membrane into the lumen of the follicle.

 4.    Iodination of tyrosine.

As iodine molecules (I2) form, they react with tyrosines that are part of thyroglobulin molecules. Binding of one iodine atom yields monoiodotyrosine (T1) and second iodination produces diiodotyrosine (T2). The TGB with attached iodine atoms, a sticky material that accumulates and is stored in the lumen of the thyroid follicle, is termed colloid.

 5.    Coupling of T1 and T2.

During the last step in the synthesis of thyroid hormone, two T2 molecules join to form T4 or one T1 and one T2 join to form T3.

    6.    Pinocytosis and digestion of colloid.

Droplets of colloid re-enter follicular cells by pinocytosis and merge with lysosomes. Digestive enzymes in the lysosomes break down TGB, cleaving off molecules of T3 and T4.

 

Figure: Thyroid hormones are synthesized by attaching iodine atoms to the amino acid tyrosine.

7. Secretion of thyroid hormones.

Because T3 and T4 are lipid-soluble, they diffuse through the plasma membrane into interstitial fluid and then into the blood. T4 normally is secreted in greater quantity than T3, but T3 is several times more potent. Moreover, after T4 enters a body cell, most of it is converted to T3 by the removal of one iodine. 

8.    Transport in the blood.

More than 99% of both the T3 and the T4 combine with transport proteins in the blood, mainly thyroxine-binding globulin (TBG). 

 ACTIONS OF THYROID HORMONES

1.    Thyroid hormones increase basal metabolic rate (BMR), the rate of oxygen consumption under standard or basal conditions (awake, at rest, and fasting), by stimulating the use of cellular oxygen to produce ATP. When the basal metabolic rate increases, cellular metabolism of carbohydrates, lipids, and proteins increases.

2.    Thyroid hormones play an important role in the maintenance of normal body temperature. Thyroid hormones stimulate the synthesis of additional sodium-potassium pumps (Na/K ATPase), which use a large amount of ATP to continually eject sodium ions (Na+) from the cytosol into the extracellular fluid and potassium ions (K+) from the extracellular fluid into the cytosol. As cells produce and use more ATP, more heat is given off, and body temperature rises. This phenomenon is called the calorigenic effect.

3.     Thyroid hormone help in the regulation of metabolism. The thyroid hormones stimulate protein synthesis and increase the use of glucose and fatty acids for ATP production. They also increase lipolysis and enhance cholesterol excretion, thus reducing blood cholesterol level.

4.     Together with human growth hormone and insulin, thyroid hormones accelerate body growth, particularly the growth of the nervous and skeletal systems. Deficiency of thyroid hormones during foetal development, infancy, or childhood causes severe mental retardation and stunted bone growth.

5.     They increase action of neurotransmitters like adrenaline and noradrenaline.

CONTROL OF THYROID HORMONE SECRETION

Thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid-stimulating hormone (TSH) from the anterior pituitary stimulates synthesis and release of thyroid hormones, as follows,

1. Low blood levels of T3 and T4 or low metabolic rate stimulate the hypothalamus to secrete TRH.

 

2. TRH enters the hypophyseal portal veins and flows to the anterior pituitary, where it stimulates thyrotrophs to secrete TSH.

 

3. TSH stimulates virtually all aspects of thyroid follicular cell activity, including iodide trapping, hormone synthesis and secretion, and growth of the follicular cells.

 

4. The thyroid follicular cells release T3 and T4 into the blood until the metabolic rate returns to normal.

 

    5.  An elevated level of T3 inhibits the release of TRH and TSH                     (negative feedback inhibition).

CALCITONIN

The hormone produced by the parafollicular cells of the thyroid gland is calcitonin (CT). CT can decrease the level of calcium in the blood by inhibiting the action of osteoclasts, the cells that break down bone extracellular matrix.