Endocrine System Introduction The endocrine system is made up of glands that produce and secrete hormones.

These hormones regulate the body's growth, metabolism (the physical and chemical processes of the body), and sexual development and function. The hormones are released into the bloodstream and may affect one or several organs throughout the body. Hormones are chemical messengers created by the body. They transfer information from one set of cells to another to coordinate the functions of different parts of the body. Each hormone has target cells , specific cells that respond to its presence. These cells possess the receptors needed to bind and "read" the hormonal message. The other hormones are treated like junk mail and ignored, because the cell lacks the receptors to read the messages they contain. The use of hormones to coordinate cellular activities in tissues in distant portions of the body is called endocrine communication . A hormone may stimulate the synthesis of an enzyme or a structural protein not already present in the cytoplasm by activating appropriate genes in the cell nucleus; increase or decrease the rate of synthesis of a particular enzyme or other protein by changing the rate of transcription or translation; or turn an existing enzyme "on" or "off" by changing its shape or structure. The nervous system also relies primarily on chemical communication, but it does not use the bloodstream to deliver messages. Instead, neurons release a neurotransmitter at a synapse very close to the target cells that bear the appropriate receptors. This form of synaptic communication is ideal for crisis management: If you are in danger of being hit by a speeding bus, the nervous system can coordinate and direct your leap to safety. The differences between the nervous and endocrine systems seem relatively clear. Both systems rely on the release of chemicals that bind to specific receptors on their target cells. The two systems share many chemical messengers; for example, norepinephrine and epinephrine are called hormones when released into the bloodstream, but neurotransmitters when released across synapses. Both systems are regulated primarily by negative feedback control mechanisms. The two systems share a common goal: to preserve homeostasis by coordinating and regulating the activities of other cells, tissues, organs, and systems

The major glands of the endocrine system are the hypothalamus, pituitary, thyroid, parathyroids, adrenals, pineal body, and the reproductive organs (ovaries and testes). The pancreas is also a part of this system; it has a role in hormone production as well as in digestion. The endocrine system is regulated by feedback in much the same way that a thermostat regulates the temperature in a room. For the hormones that are regulated by the pituitary gland, a signal is sent from the hypothalamus to the pituitary gland in the form of a "releasing hormone," which stimulates the pituitary to secrete a "stimulating hormone" into the circulation. The stimulating hormone then signals the target gland to secrete its hormone. As the level of this hormone rises in the circulation, the hypothalamus and the pituitary gland shut down secretion of the releasing hormone and the stimulating hormone, which in turn slows the secretion by the target gland. This system results in stable blood concentrations of the hormones that are regulated by the pituitary gland. Hypothalamus The hypothalamus is located in the lower central part of the brain. This part of the brain is important in regulation of satiety, metabolism, and body temperature. In addition, it secretes hormones that stimulate or suppress the release of hormones in the pituitary gland. Many of these hormones are releasing hormones, which are secreted into an artery(the hypophyseal portal system) that carries them directly to the pituitary gland. In the pituitary gland, these releasing hormones signal secretion of stimulating hormones. The hypothalamus also secretes a hormone calledsomatostatin, which causes the pituitary gland to stop the release of growth hormone. Pituitary Gland The pituitary gland is located at the base of the brain beneath the hypothalamus and is no larger than a pea. It is often considered the most important part of the endocrine system because it produces hormones that control many functions of other endocrine glands. When the pituitary gland does not produce one or more of its hormones or not enough of them, it is called hypopituitarism. The pituitary gland is divided into two parts: the anterior lobe and the posterior lobe. The anterior lobe produces the hormones, which are regulated by the hypothalamus: Thyroid-stimulating hormone (TSH) - Stimulates the thyroid gland to produce thyroid hormones. TSH is released in response to thyrotropin releasing hormone (TRH) from the hypothalamus. As circulating concentrations of thyroid hormones rise, the rates of TRH and TSH production decline. (A lack of thyroid hormones either

because of a defect in the pituitary or the thyroid itself is called hypothyroidism.) Thyroid Gland The thyroid gland is located in the lower front part of the neck below the Adam's apple. It produces thyroid hormones that regulate the body's metabolism. These hormones then travel through the bloodstream to all the other tissues and organs to help control metabolism in adults and growth, metabolism and development of the brain and nervous system in children. The pituitary gland controls the release of thyroid hormones. Thyroid hormones also help maintain normal blood pressure, heart rate, digestion, muscle tone, and reproductive functions. The thyroid is shaped like a butterfly. The two "wings" of the butterfly are the right and left lobes of the thyroid, with lie on both sides of the trachea or main breathing tube. The connection between the wings is called the isthmus. The two hormones that the thyroid produces are L-thyroxine(T4) and triiodothyronine (T3).

The thyroxine (T4) and tri-iodothyronine (T3) hormones regulate your body's metabolic functions such as heat generation, and the utilization ofcarbohydrates, proteins, and fats. In children, thyroid hormones are responsible for growth and development. Regulatory hormones from different parts of the brain control the thyroid's production of T4 and T3. In the pituitary gland, thyrotropin-stimulating hormone (TSH) is released when more thyroid hormone is needed and travels via the bloodstream to the thyroid gland. TSH then stimulates the thyroid to produce T4 and T3. The pituitary gland acts like a thermostat. When there is too much thyroid hormone in the bloodstream, the pituitary releases less TSH to signal the thyroid to produce less thyroid hormone. When there is too little thyroid hormone in the bloodstream, the pituitary releases more TSH to signal the thyroid to increase thyroid hormone production. Through this "feedback" system, the production of thyroid hormone is tightly controlled.

Location and picture of the thyroid gland. Note two lobes of the thyroid, similar to butterfly wings.

The Thyroid Gland curves across the anterior surface of the trachea just inferior to the thyroid cartilage , which forms most of the anterior surface of the larynx

The two lobes of the thyroid gland are united by a slender connection, the isthmus. Thyroid Follicles and Thyroid Hormones The thyroid gland contains large numbers of thyroid follicles, spheres lined by a simple cuboidal epithelium. Follicle cells synthesize a globular protein called thyroglobulin and secrete it into the colloid of the thyroid follicles. Each thyroglobulin molecule contains the amino acid tyrosine, the building block of thyroid hormones.

The formation of thyroid hormones involves three basic steps: 1. Iodide ions are absorbed from the diet at the digestive tract and are delivered to the thyroid gland by the bloodstream. Carrier proteins in the basal membrane of the follicle cells transport iodide ions into the cytoplasm. Normally, the follicle cells maintain intracellular concentrations of iodide that are many times higher than those in the extracellular fluid. 2. The iodide ions diffuse to the apical surface of each follicle cell, where they are converted to an activated form of iodide by the enzyme thyroid peroxidase . This reaction sequence also attaches one or two iodide ions to the tyrosine molecules of thyroglobulin. 3. Tyrosine molecules to which iodide ions have been attached are paired, forming molecules of thyroid hormones that remain incorporated into thyroglobulin. The pairing process is probably performed by thyroid peroxidase. The hormone thyroxine, also known as tetraiodothyronine , or

contains four iodide ions. Triiodothyronine , or is a related molecule containing three iodide ions. Eventually, each molecule of thyroglobulin contains four to eight molecules of or hormones or both.

The major factor controlling the rate of thyroid hormone release is the concentration of TSH in the circulating blood . TSH stimulates iodide transport into the follicle cells and stimulates the production of thyroglobulin and thyroid peroxidase. TSH also stimulates the release of thyroid hormones. Under the influence of TSH, the following steps occur: 1. Follicle cells remove thyroglobulin from the follicles by endocytosis. 2. Lysosomal enzymes break the thyroglobulin down, and the amino acids and thyroid hormones enter the cytoplasm. The amino acids are then recycled and used to synthesize thyroglobulin. 3. The released molecules of T3 and T4 diffuse across the basement membrane and enter the bloodstream. About 90 percent of all thyroid secretions is is secreted in comparatively small amounts. 4. Roughly 75 percent of the T4 molecules and 70 percent of the T3 molecules entering the bloodstream become attached to transport proteins called thyroidbinding globulins ( TBGs ). Most of the rest of the T4and T3 in the circulation is attached to transthyretin , also known as thyroidbinding prealbumin ( TBPA ), or to albumin , one of the plasma proteins. Only the relatively small quantities of thyroid hormones that remain unboundroughly 0.3 percent of the circulating T3 and 0.03 percent of the circulating T4 are free to diffuse into peripheral tissues. Functions of Thyroid Hormones Thyroid hormones readily cross cell membranes, and they affect almost every cell in the body. Inside a cell, they bind to (1) receptors in the cytoplasm, (2) receptors on the surfaces of mitochondria, and (3) receptors in the nucleus. Thyroid hormones bound to cytoplasmic receptors are essentially held in storage. If intracellular levels of thyroid hormones decline, the bound thyroid hormones are released into the cytoplasm. The thyroid hormones binding to mitochondria increase the rates of mitochondrial ATP production. The binding to receptors in the nucleus activates genes that control the synthesis of enzymes involved with energy transformation and utilization. One specific effect of binding to nuclear receptors is the accelerated production of sodium potassium ATPase, the membrane protein responsible for the ejection of intracellular sodium and the recovery of extracellular potassium. As we noted in Chapter 3 , this exchange pump consumes large amounts of ATP. Thyroid hormones also activate genes that code for the synthesis of enzymes involved in glycolysis and ATP production. This effect, coupled with the direct effect

of thyroid hormones on mitochondria, increases the metabolic rate of the cell. Because the cell consumes more energy and because energy use is measured in calories , the effect is called the calorigenic effect of thyroid hormones. When the metabolic rate increases, more heat is generated. In young children, TSH production increases in cold weather; the calorigenic effect may help them adapt to cold climates. (This response does not occur in adults.) In growing children, thyroid hormones are also essential to normal development of the skeletal, muscular, and nervous systems. T3 Versus T4 The thyroid gland produces large amounts of T4 but T3 is primarily responsible for the observed effects of thyroid hormones: a strong, immediate, and shortlived increase in the rate of cellular metabolism. Peripheral tissues have two sources of T3 1. Release by the Thyroid Gland . At any moment, T3 from the thyroid gland accounts for only 1015 percent of the in peripheral tissues. 2. The Conversion of to Enzymes in the liver, kidneys, and other tissues can convert T4 to T3. Roughly 8590 percent of the T3 that reaches the target cells is produced by the conversion of T4 within peripheral tissues.

Iodine and Thyroid Hormones Iodine in the diet is absorbed at the digestive tract. The thyroid follicles contain most of the iodide reserves in the body. The typical diet in the United States provides approximately 500ug of iodide per day, roughly three times the

minimum daily requirement. Much of the excess is due to the addition of to the table salt sold in grocery stores as "iodized salt." Thus, iodide deficiency is seldom responsible for limiting the rate of thyroid hormone production. (This is not necessarily the case in other countries.) Excess is removed from the blood at the kidneys, and each day a small amount of (about 20ug ) is excreted by the liver into the bile, an exocrine product stored in the gallbladder. Iodide excreted at the kidneys is eliminated in urine; the iodine excreted in bile is eliminated with intestinal wastes. The C Cells of the Thyroid Gland: Calcitonin A second population of endocrine cells lies sandwiched between the cuboidal follicle cells and their basement membrane. These cells, which are larger than those of the follicular epithelium and do not stain as clearly, are theC ( clear ) cells , or parafollicular cells. C cells produce the hormone calcitonin ( CT ), which aids in the regulation of concentrations in body fluids. We introduced the functions of this hormone in Chapter 6 . The net effect of calcitonin release is a drop in the concentration in body fluids, accomplished by (1) the inhibition of osteoclasts, which slows the rate of release from bone, and (2) the stimulation and then falloff of excretion at the kidneys. Calcitonin is probably most important during childhood, when it stimulates bone growth and mineral deposition in the skeleton. It also appears to be important in reducing the loss of bone mass (1) during prolonged starvation and (2) in the late stages of pregnancy, when the maternal skeleton competes with the developing fetus for calcium ions absorbed by the digestive tract. Thyroid Gland Disorders Normal production of thyroid hormones establishes the background rates of cellular metabolism. These hormones exert their primary effects on metabolically active tissues and organs, including skeletal muscles, the liver, and the kidneys. The inadequate production of thyroid hormones is called hypothyroidism . In an infant, hypothyroidism produces cretinism , a condition marked by inadequate skeletal and nervous development and a metabolic rate as much as 40 percent below normal levels. The condition affects approximately 1 birth out of every 5000. Cretinism developing later in childhood will retard growth and mental development and delay puberty. Adults with hypothyroidism are lethargic and unable to tolerate cold temperatures. The symptoms of adult hypothyroidism, collectively known as myxedema, include subcutaneous swelling, dry skin, hair loss, low body temperature, muscular weakness, and slowed reflexes. Hypothyroidism may also be associated with the enlargement of the thyroid gland, producing a distinctive swelling called a goiter. Hypothyroidism, myxedema, and goiter as the result of inadequate dietary iodide are very rare in the United States, in part due to the

addition of iodine to table salt, but these conditions can be relatively common in poorer countries, especially landlocked ones (seafood is a good source of iodine).

Thyroid Disorders. (a) Cretinism, or congenital hypothyroidism, results from thyroid hormone insufficiency in infancy. (b) An enlarged thyroid gland, or goiter, can be associated with thyroid hyposecretion due to iodine insufficiency in adults. Hyperthyroidism , or thyrotoxicosis , occurs when thyroid hormones are produced in excessive quantities. The metabolic rate climbs, and the skin becomes flushed and moist with perspiration. Blood pressure and heart rate increase, and the heartbeat may become irregular as circulatory demands escalate. The effects on the central nervous system make the individual restless, excitable, and subject to shifts in mood and emotional states. Despite the drive for increased activity, the person has limited energy reserves and fatigues easily. Graves' disease is a form of hyperthyroidism that afflicted President George W. H. Bush and Barbara Bush during their stay in the White House.

Thyroid gland

The Thyroid gland is one of the largest endocrine glands in the body. It is positioned on the neck just below the Larynx and has two lobes with one on either side of the trachea. It is involved in the production of the hormones T3 (triiodothyronine) and T4 (thyroxine). These hormones increase the metabolic activity of the bodys cells. The thyroid also produces and releases the hormone calcitonin (thyrocalcitonin) which contributes to the regulation of blood calcium levels. Thyrocalcitonin or calcitonin decreases the concentration of calcium in the blood. Most of the calcium removed from the blood is stored in the bones. The thyroid hormone consists of two components, thyroxine and iodine. This hormone increases the metabolism of most body cells. A deficiency of iodine in the diet leads to the enlargement of the thyroid gland, known as a simple goiter. Hypothyroidism during early development leads to cretinism. In adults, it produces myxedema, characterized by obesity and lethargy. Hyperthyroidism leads to a condition known as exophthalmic goiter, characterized by weight loss as well as hyperactive and irritable behavior. The thyroid gland is a two-lobed gland that manifests a remarkably powerful active transport mechanism for up-taking iodide ions from the blood. As blood flows through the gland, iodide is converted to an active form of iodine. This iodine combines with an amino acid called tyrosine. Two molecules of iodinated tyrosine then combine to form thryroxine. Following its formation, the thyroxine becomes bound to a polysaccharide-protein material called thyroglobulin. The normal thyroid gland may store several weeks supply of thyroxine in this bound form. An enzymatic splitting of the thyroxine from the thyroglobulin occurs when a specific hormone is released into the blood. This hormone, produced by the pituitary gland, is known as thyroid-stimulating hormone (TSH). TSH stimulates certain major rate-limiting steps in thyroxine secretion, and thereby alters its rate of release. A variety of bodily defects, either dietary, hereditary, or disease induced, may decrease the amount of thyroxine released into the blood. The most popular of these defects is one that results from dietary iodine deficiency. The thyroid gland enlarges, in the continued presence of TSH from the pituitary, to form a goiter. This is a futile attempt to synthesize thyroid hormones, for iodine levels that are too low. Normally, thyroid hormones act via a negative feedback loop on the pituitary to decrease stimulation of the thyroid. In goiter, the feedback loop cannot be in operation - hence continual stimulation of the thyroid and the inevitable protuberance on the neck. Formerly, the principal source of iodine came from seafood. As a result, goiter was prevalent amongst inland areas far removed from the sea. Today, the incidence of goiter has been drastically reduced by adding iodine to table salt. Thyroxine serves to stimulate oxidative metabolism in cells; it increases the oxygen consumption and heat production of most body tissues, a notable exception being the brain. Thyroxine is also necessary for normal growth. The most likely explanation being that thyroxine promotes the effects of growth hormone on protein synthesis. The absence of thyroxine significantly reduces the ability of growth hormone to stimulate amino acid uptake and RNA synthesis. Thyroxine also

plays a crucial role in the closely related area of organ development, particularly that of the central nervous system. If there is an insufficient amount of thyroxine, a condition referred to as hypothyroidism results. Symptoms of hypothyroidism stem from the fact that there is a reduction in the rate of oxidative energy-releasing reactions within the body cells. Usually the patient shows puffy skin, sluggishness, and lowered vitality. Other symptoms of hypothyroidism include weight gain, decreased libido, inability to tolerate cold, muscle pain and spasm, insomnia and brittle nails. Hypothyroidism in children, a condition known as cretinism, can result in mental retardation, dwarfism, and permanent sexual immaturity. Sometimes the thyroid gland produces too much thyroxine, a condition known as hyperthyroidism. This condition produces symptoms such as an abnormally high body temperature, profuse sweating, high blood pressure, loss of weight, irritability, and muscular pain and weakness. It also causes the characteristic symptom of the eyeballs protruding from the skull called exopthalmia. This is surprising because it is not a symptom usually related to a fast metabolism. Hyperthyroidism has been treated by partial removal or by partial radiation destruction of the gland. More recently, several drugs that inhibit thyroid activity have been discovered, and their use is replacing the former surgical procedures. Unfortunately thyroid conditions require lifetime treatment and because of the body's need for a sensitive balance of thyroid hormone both supplementing and suppressing thyroid function can take months or even years to regulate. T3 and T4 Function within the body The Production of T3 and T4 are regulated by thyroid stimulating hormone (TSH), released by the pituitary gland. TSH Production is increased when T3 and T4 levels are too low. The thyroid hormones are released throughout the body to direct the body's metabolism. They stimulate all cells within the body to work at a better metabolic rate. Without these hormones the body's cells would not be able to regulate the speed at which they performed chemical actions. Their release will be increased under certain situations such as cold temperatures when a higher metabolism is needed to generate heat. When children are born with thyroid hormone deficiency they have problems with physical growth and developmental problems. Brain development can also be severely impaired The significance of iodine Thyroid hormone cannot be produced without an abundant source of iodine. The iodine concentration within the body, although significant, can be as little as 1/25th the concentration within the thyroid itself. When the thyroid is low on iodine the body will try harder to produce T3 and T4 which will often result in a swelling of the thyroid gland, resulting in a goiter.

Secretion and Distribution of Hormones Hormone release typically occurs where capillaries are abundant, and the hormones quickly enter the bloodstream for distribution throughout the body. A freely circulating hormone remains functional for less than one hour, and sometimes for as little as two minutes. It is inactivated when (1) it diffuses out of the bloodstream and binds to receptors in target tissues, (2) it is absorbed and broken down by cells of the liver or kidneys, or (3) it is broken down by enzymes in the plasma or interstitial fluids. Thyroid hormones and steroid hormones remain in circulation much longer, because when these hormones enter the bloodstream, almost all of them become attached to special transport proteins. Thus, the bloodstream contains a substantial reserve (several weeks' supply) of these hormones at any time.