The thyroid gland is butterfly shaped and sits on the trachea, in the anterior neck.

It is comprised of two lobes connected in the middle by an isthmus. Inside, the gland is made up of many hollow follicles, whose epithelial cell walls (also known as follicle cells) surround a central cavity filled with a sticky, gelatinous material called colloid. Para follicular cells are found in the follicle walls, protruding out into the surrounding connective tissue. The thyroid is the largest exclusively endocrine gland in the body. The endocrine system is the bodys communication hub, controlling cell, and therefore organ, function. A primary goal of the endocrine system is to maintain homeostasis within the organism, despite external fluctuations of any sort. Hormones, which act as chemical messengers, are the mechanism for this communication.

The hormones secreted by the thyroid gland are essential in this process, targeting almost every cell in the body (only the adult brain, spleen, testes, and uterus are immune to their effects.) Inside cells, thyroid hormone stimulates enzymes involved with glucose oxidation, thereby controlling cellular temperature and metabolism of proteins, carbohydrates, and lipids. Through these actions, the thyroid regulates the bodys metabolic rate and heat production. Thyroid hormone also raises the number of adrenergic receptors in blood vessels, thus playing a major role in the regulation of blood pressure. In addition, it promotes tissue growth, and is particularly vital in skeletal, nervous system, and reproductive development. The two major thyroid hormones (TH) are unique in that, unlike most hormones, they are neither protein nor cholesterol based. Instead, they incorporate iodine as an active constituent; the amount of iodine differentiates between thyroxine (also known as tetraiodothyronine or T4) with four iodine molecules and triodothyronine (T3) with, predictably, three iodine molecules. While T4 exists in greater abundance than T3 in the body- thought to be at a fifty to one ratio, T3 is considered to be ten times more active. There is much debate about the physiological difference between the two hormones. It is currently thought that T4 may act as the reserve form, having a more direct role in the hypothalamus/pituitary negative feedback loop, while T3 has a more dynamic physiological effect in the body. Others suggest that both have a critical part in physiological activity.

TH (particularly T4) is synthesized in the glands colloid filled lumen from the combination of the glycoprotein thyroglobulin and stored iodine atoms. This process involves six interrelated steps that are initiated when thyroid stimulating hormone (TSH), released by the pituitary gland, binds to follicle cell receptors. Thyroglobulin is then made in the follicle cells from tyrosine amino acid and discharged into the lumen where it becomes part of the colloid mass. Follicle cells are simultaneously trapping iodide (the elements form most readily available in food) from the blood stream- retrieving it via active transport from the lumen. There, the iodides are converted to iodine as electrons are removed through oxidation. Within the colloid, the iodine then attaches to tyrosine amino acid on the thyroglobulin molecules. When one iodine attaches to the tyrosine, monoiodotyrosine (T1) is formed; the bonding of a second iodine creates diiodotyrosine (T2). Enzymes then link T1 and T2- two T2 makes the hormone T4, while a T1 and a T2 leads to the hormone T3. Follicle cells then recover the hormones, where they pass through an enzymatic process and are then released into the bloodstream. However, the majority of the bodys T3 is made directly on the tissue level, as target cells use enzymes to remove one iodine atom from the T4 molecules made in the thyroid, converting them to T3 before use. Most of the alteration occurs in the liver, using enzyme 5deiodinase. In its behavior, TH functions somewhat similarly to steroid hormones. As it is not water soluble, it requires a protein-based molecule for transport throughout the blood stream. T3 and T4 will generally pair with thyroxine binding globulin (TBG) for this purpose, though they can also use albumin and prealbumin. At any given moment, the vast majority of TH in the body is in this bound, and essentially inactive, state, either in route or awaiting transport. The small percentage of unbound, physiologically active hormone is called free T3 or T4. It appears that TBG and albumin have higher affinity for T4, which could explain T4s higher levels in blood and its slower metabolism, and perhaps account for free T3 being the more physiologically active substance. The main site of TH degradation is in the liver and its primary elimination is via kidneys (80%, the other 20% is via the colon.) When TH enters a cell, it attaches to receptor sites in various locations. Within the cytoplasm, it primarily connects to the mitochondria, where it helps control cellular metabolism through oxidative phosphorolation. During this process the mitochondria use oxygen to generate energy as ATP (Adenosine triphosphate); heat is released as a byproduct of this reaction. Thus, the thyroid (under higher regulation as we will see below) controls body temperature and food metabolism through its role in stimulating mitochondrial activity. TH also enters the cell nucleus where it binds to DNA; here it precipitates gene transcription, and the synthesis of messenger RNA and cytoplasmic proteins. Other hormones, including Growth Hormone (GH) and Prolactin, also depend on the presence of TH to exert their own effects on cells; the absence of TH inhibits their activity.

Messages from the anterior pituitary gland are the main stimulus for the action of the thyroid gland. The pituitary gland, in turn, is triggered from above by the hypothalamus. The three organs are connected in a negative feedback loop that involves their vigilant monitoring of and response to the levels of TH in the blood, as well as other internal and external stimuli; this relationship is sometimes referred to as the hypothalamic-pituitary-thyroid axis. The hypothalamus secretes protein hormone thyrotropin-releasing hormone (TRH), which heads directly to the pituitary gland via the hypophysial portal blood system, stimulating the release of TSH. TSH then moves through the bloodstream, binding with receptors in the thyroid gland, prompting the secretion of TH into the blood. Both T4 and T3 then exert a negative feedback effect on the hypothalamus and pituitary- an increase in their blood levels lowers the amount of TRH and TSH secreted and a decrease in their levels causes a rise in the TRH and TSH. Stimuli to the higher brain including temperature and stress can also effect TRH production in the hypothalamus; for instance, cold temperatures can increase the bodys requirements for TH as more internal heat will be need to maintain homeostasis and the hypothalamus reacts accordingly. Stress affects the thyroid gland not only through the hypothalamus, but also directly via the sympathetic nervous system. There are sympathetic nerves that connect with the gland; during their stimulation in times of stress, they trigger increased TH release. In addition, it appears that epinephrine from the adrenal gland can also act directly on the thyroid. Diet can affect thyroid function, as a high calorie/high carbohydrate diet can lead to increased conversion of T4 to T3- a mechanism that likely assists in keeping an organisms weight stable. Meanwhile, prolonged fasting can result in a decrease in T3 production- which may be adaptive for conditions of food scarcity, slowing down the bodys metabolism and energy consumption. SIGNIFICANCE OF IODINE: In areas of the world where iodine is lacking in the diet the thyroid gland can become considerably enlarged, a condition called endemicgoiter. Pregnant women on a diet that is severely deficient of iodine can give birth to infants who can present with thyroid hormone deficiency (congenital hypothyroidism), manifesting in problems of physical growth and development as well as brain development (a condition referred to as endemic cretinism). In many developed countries, newborns are routinely tested for congenital hypothyroidism as part of newborn screening. Children with congenital hypothyroidism are treated supplementally with levothyroxine, which facilitates normal growth and development.Thyroxine is critical to the regulation of metabolism and growth throughout the animal kingdom. Among amphibians, for example, administering a thyroid-blocking agent such as propylthiouracil (PTU) can prevent tadpoles from metamorphosing into frogs; in contrast, administering thyroxine will trigger metamorphosis.

Because the thyroid concentrates this element, it also concentrates the various radioactive isotopes of iodine produced by nuclear fission. In the event of large accidental releases of such material into the environment, the uptake of radioactive iodine isotopes by the thyroid can, in theory, be blocked by saturating the uptake mechanism with a large surplus of non-radioactive iodine, taken in the form of potassium iodide tablets. One consequence of the Chernobyl disaster was an increase in thyroid cancers in children in the years following the accident.[28] The use of iodised salt is an efficient way to add iodine to the diet. It has eliminated endemic cretinism in most developed countries, and some governments have made the iodination of flour, cooking oil, and salt mandatory. Potassium iodide and sodium iodide are typically used forms of supplemental iodine. As with most substances, either too much or too little can cause problems. Recent studies on some populations are showing that excess iodine intake could cause an increased prevelence of autoimmune thyroid disease, resulting in permanent hypothyroidism. BIBLIOGRAPHY: http://www.ohlonecenter.org/research-papers/the-thyroid-gland-anatomy-physiology/