Chapter 17 Endocrine System PDF

INTEGRATE connective tissue cells respond to TH by both increasing lipolysis and decreasing lipogenesis (see section 2.7b)...

INTEGRATE connective tissue cells respond to TH by both increasing lipolysis and decreasing lipogenesis (see section 2.7b). As a result, both glycerol and CONCEPT CONNECTION fatty acids are released into blood as alternative nutrient molecules for cellular respiration. This saves blood glucose for the brain and is called The second law of thermodynamics (see section 3.1c) helps explain the the g­ lucose-sparing effect. relationship between increased TH and an increase in body temperature. TH Respiration rate increases in response to TH to meet the additional stimulates the synthesis of sodium-potassium (Na+/K+) pumps to move these demands for oxygen. Additionally, both heart rate and force of heart ions across the membrane. Chemical energy in the form of ATP is converted to contraction increase blood flow to the tissues to deliver more nutrients mechanical energy to power the pumps. The second law of thermo- and oxygen. This is a result of the cardiac muscle cells increasing their dynamics states that heat is produced during any energy conversion. With number of cellular receptors for the hormones epinephrine and norepi- greater numbers of Na+/K+ pumps, more chemical energy is converted to nephrine, ensuring that the heart continues to be more responsive to mechanical energy, additional heat is produced, and body temperature rises. these hormones (see section 19.9b). Additional responses to the release of thyroid hormone are listed in the s­ ummary table on thyroid hormone in the reference section, which directly follows this chapter (see table R.4). in temperature is referred to as the calorigenic (kă-lōr′i-jen′ik; WHAT DO YOU THINK? calor = heat, genesis = ­production) effect. Increased amino acid uptake by cells provides the structural building blocks for these processes. TH 7 Predict the signs and symptoms that a person with hyperthyroidism would exhibit in each of the following circumstances: (a) high temperature also stimulates all cells to increase their glucose uptake. Concomitant or low temperature, (b) elevated pulse or decreased pulse, (c) elevated with this increase is buildup in the number of cellular respiration breathing or decreased breathing, and (d) plump or thin body. enzymes within mitochondria because additional ATP is needed to sup- port the higher metabolic rate. TH stimulates other target cells to help meet the additional require- WHAT DID YOU LEARN? ments for ATP. Hepatocytes are stimulated to increase both glyco- 22 What is the relationship of TRH, TSH, and TH in regulating metabolism? genolysis and gluconeogenesis (see section 2.7c), while glycogenesis is 23 What are the primary target organs and tissues of TH? Describe the inhibited, thus additional glucose is released into the blood. Adipose effect on each. INTEGRATE CLINICAL VIEW 17.5 does the thyroid. Patients whose thyroid glands have been removed or destroyed must take daily hormone supplements. Disorders of Thyroid Hormone Secretion Hypothyroidism results from decreased production of TH. It is characterized by low metabolic rate, lethargy, a feeling of being cold, weight gain (in some Thyroid hormone (TH) release is very tightly controlled in the healthy state, but patients), and photophobia (the disdain and avoidance of light). Hypothyroidism should the amount vary by even a little, a person could become either hyperactive may be caused by decreased iodine intake, loss of pituitary stimulation of the and heat-intolerant or sluggish and overweight. Disorders of thyroid activity are thyroid, post-therapeutic hypothyroidism (resulting from either surgical removal among the most common metabolic problems clinicians see. or radioactive iodine treatments), or destruction of the thyroid by the person’s own Hyperthyroidism results from excessive production of TH and is characterized immune system (Hashimoto thyroiditis). Oral replacement of TH may be needed by increased metabolic rate, weight loss, hyperactivity, and heat intolerance. Although for most of these cases of hypothyroidism. there are a number of causes of hyperthyroidism, the more common ones are A goiter is the enlargement of the thyroid, typically due to an insufficient (a) ingestion of T4 (weight control clinics sometimes use TH to increase metabolic amount of dietary iodine. Although the pituitary releases more TSH in an effort activity); (b) excessive stimulation of the thyroid by the pituitary gland; and (c) loss to stimulate the thyroid, the lack of of feedback control by the thyroid. This last condition, called Graves disease, is dietary iodine prevents the thyroid an autoimmune disorder involving the formation of autoantibodies that mimic from producing the needed TH. The TSH hormone. The autoantibodies bind to TSH receptors on the follicular cells of long-term consequence of the the thyroid, causing an abnormally high level of TH release. Graves disease excessive TSH stimulation is includes all the symptoms of hyperthyroidism plus protruding and bulging eyeballs overgrowth of the thyroid follicles known as exophthalmos (ek′sof-thal′mos; ex = out; ophthalmos = eye). and the thyroid itself. Goiter was a Hyperthyroidism is treated by removing the thyroid gland, either by surgery or relatively common deformity in the by intravenous injections of radioactive iodine (I-131). In the procedure for treating United States until food processors hyperthyroidism, the thyroid gland cells are destroyed as the organ sequesters began adding iodine to table salt. the I-131, but other organs are not damaged because they do not store iodine as It still occurs in parts of the world where iodine is lacking in the diet and, as such, is referred to as endemic goiter. Unfortunately, goiters do not readily regress once iodine is restored to the diet, and surgical removal of part or all of the thyroid gland is often required. Goiter. Exophthalmos seen in Graves disease. ©Scott Camazine/Science Source ©Chris Barry/Medical Images 678 Chapter Seventeen Endocrine System 17.8c Calcitonin: Its Regulation and Effects Adrenal Cortex Gross Anatomy The adrenal cortex exhibits a distinctive yellow color as a conse- LEARNING OBJECTIVE quence of the stored lipids within its cells. These cells synthesize 28. Explain the role of calcitonin in regulating blood calcium. more than 25 different lipid-soluble corticosteroids (see section 17.3a). The adrenal cortex is partitioned into three separate Calcitonin is synthesized and released from the parafollicular cells regions: the outer zona glomerulosa, the middle zona fasciculata, of the thyroid gland (see figure 17.15b). The stimulus for calcitonin and the inner zona reticularis (figure 17.18c). Different functional release from parafollicular cells is a high blood calcium level; it is categories of steroids are synthesized and secreted in the separate also secreted in response to stress from exercise. Calcitonin primarily zones. inhibits osteoclast activity within bone tissue (which decreases the breakdown of bone tissue) and stimulates the kidneys to increase the loss of calcium in the urine. The net effect of calcitonin is a reduction Adrenal Cortex Histology and Hormones in blood calcium levels. Calcitonin seems to have the greatest effect The zona glomerulosa (zō′nă glō-mĕr-ū-lōs′ă; glomerulus = ball of in the bones of growing children, where there is the greatest turnover yarn) is the thin, outer cortical layer composed of dense, spherical of bone. The relationship of calcitonin to parathyroid hormone and clusters of cells. These cells synthesize m ­ ineralocorticoids (min′er- calcitriol in regulating blood calcium is discussed in section 7.6c. al-ō-kōr′ti-koyd), a group of hormones that help regulate the compo- sition and concentration of electrolytes (ions) in body fluids. The principal mineralocorticoid is aldosterone (al-dos′ter- ōn), which WHAT DID YOU LEARN? regulates the ratio of Na+ and K+ in our blood and body fluids by 24 Does calcitonin decrease or increase blood calcium? Explain. altering the amounts excreted by the kidney into the urine. Aldoste- rone stimulates retention of both Na+ and water and the secretion of K+. Thus, the Na+ blood concentration remains the same (because of the retention of both Na+ and water), and K+ blood concentration decreases. Severe imbalances in this ratio can result in death. The functional details of aldosterone are described in sections 24.6d and 17.9 Adrenal Glands 25.4c and summarized in the reference tables following this chapter The adrenal glands, like the hypothalamus and pituitary gland, are com- (see table R.7). posed of both nervous tissue and endocrine tissue. The inner portion of The zona fasciculata (f ă-sik′ū-la′tă; fascicle = bundle of paral- each gland, called the adrenal medulla, is composed of nervous tissue. lel sticks) is the middle layer and largest region of the adrenal cortex. The outer portion, called the adrenal cortex, is composed of endocrine It is composed of parallel cords of lipid-rich cells that have a bubbly, tissue. Numerous types of hormones are released from this gland. We almost pale appearance. This region synthesizes glucocorticoids first describe adrenal gland anatomy and its associated hormones. (glū′kō-kōr-ti-koyd). The main glucocorticoids synthesized in this region are cortisol and corticosterone, which are released in response to ACTH. Details of cortisol regulation and function are 17.9a Anatomy of the Adrenal Glands described in section 17.9b. The innermost region of the cortex, the zona reticularis LEARNING OBJECTIVES ­(rĕ-tik′ū-lăr′is; reticulum = network), is a narrow band of small, 29. Describe the structure and location of the adrenal glands. branching cells. They are capable of secreting minor amounts of sex 30. Name the three zones of the adrenal cortex and the hormones produced in hormones called gonadocorticoids. The primary gonadocorticoids each zone. secreted are male sex hormones called androgens, thus serving as a secondary site for androgens in males and the primary site in The adrenal (ă-drē′n ăl; ad = to, ren = kidney) glands, or suprarenal females. Gonadocorticoids include dehydroepiandrosterone glands, are paired, ­pyramid-shaped endocrine glands anchored on the (DHEA), DHEA-sulfate, and androstenedione. The amount of superior surface of each kidney (­figure 17.18). Each adrenal gland androgen secreted by the adrenal cortex is small compared to that is enclosed within a connective tissue capsule. These glands (like the secreted by the gonads; however, adrenal gland tumors in a female kidney that each is superior to) are retroperitoneal, which is posterior can result in elevated levels of androgens and varying degrees of to the parietal peritoneum (see section 24.2a). Each adrenal gland is masculinization. embedded within fat and fascia to minimize their movement. The adrenal medulla and adrenal cortex of an adrenal gland are shown in WHAT DID YOU LEARN? figure 17.18b. 25 Which category of hormones is produced by the zona fasciculata of the Adrenal Medulla adrenal cortex? The adrenal medulla forms the inner core of each adrenal gland. It has a pronounced red-brown color due to its extensive vasculariza- tion. It releases the catecholamines epinephrine and norepineph- rine (which are biogenic amines; see section 17.3a). The stimulus for INTEGRATE the release of these hormones is activation by the sympathetic divi- sion (see figure 17.3c). Approximately 80% of the hormone released LEARNING STRATEGY 17.3 is epinephrine and about 20% is norepinephrine. Both hormones cir- culate within the blood and help prolong the fight-or-flight response, You can remember the primary functions of the three layers of the adrenal which is caused by the activation of the sympathetic division (see cortex (from outermost to innermost) with the following: “salt, sugar, and sex.” section 15.4). Chapter Seventeen Endocrine System 679 Adrenal gland Right adrenal gland Diaphragm Left renal vein Right renal vein Inferior vena cava Abdominal aorta Right kidney (a) Anterior view of posterior abdominal wall Capsule Adrenal cortex Adrenal medulla Capsule Capsule Zona glomerulosa (b) Adrenal gland (sectioned) Zona fasciculata Adrenal cortex Zona reticularis Adrenal medulla Adrenal medulla LM 35x (c) Microscopic view of adrenal cortex Figure 17.18 Adrenal Glands. Each adrenal gland is a two-part gland that secretes stress-related hormones. The adrenal medulla produces epinephrine and norepinephrine, and the adrenal cortex produces mineralocorticoids (e.g., aldosterone), glucocorticoids (e.g., cortisol), and gonadocorticoids (e.g., androgens) from its different zones. (a) A cadaver photo shows the relationships of the kidneys and adrenal glands. (b) A sectioned adrenal gland shows the capsule, outer cortex and inner medulla. (c) A diagram and a micrograph illustrate the three zones of the adrenal cortex, as well as the relationship of the cortex to the external capsule and the internal medulla. (a) ©McGraw-Hill Education/Christine Eckel; (c) ©McGraw-Hill Education/Alvin Telser 680 Chapter Seventeen Endocrine System  17.9b Cortisol: Its Regulation and Effects pituitary. This physiologic relationship is referred to as the hypothalamic-pituitary-adrenal axis, which was first described in LEARNING OBJECTIVE section 17.7c. 31. Describe the homeostatic system involving cortisol. The hypothalamus releases corticotropin-releasing hormone (CRH), which is transported through the hypothalamo-hypophyseal This section provides a detailed examination of the homeostatic sys- portal system to the anterior pituitary (steps 1-3). CRH binds to recep- tem involving cortisol. We describe its regulated release by the ante- tors of the anterior pituitary (corticotropic cells) and stimulates the rior pituitary and its effects (as a lipid-soluble hormone) on its target release of adrenocorticotropic hormone (ACTH) into general circu- cells. Please refer to figure 17.19, as you read through this section lation (step 4). ACTH then binds to receptors within adrenal cortex and note that each of the indicated steps are illustrated in this figure. cells (zona fasciculata) and stimulates the release of glucocorticoids including cortisol (kōr′ti-sol) and corticosterone (kōr′ti-kos′ter-ōn) Regulation of Cortisol Release (step 5). Cortisol accounts for 95% of the glucocorticoid activity. Cor- Cortisol and corticosterone are released from the adrenal cortex as tisol is transported within the blood by carrier proteins (corticosteroid- a result of the integrated activities of the hypothalamus and anterior binding globulin [or CBG, also called transcortin] or albumin). Cortisol STIMULUS Stimulation Inhibition Figure 17.19 1 Variables that influence the release of CRH from the hypothalamus: Regulation and Blood levels of cortisol Action of Cortisol Time of day Stress Hormone. The hypothalamus responds to particular stimuli by Hypothalamus releasing corticotropin- 1 releasing hormone 2 (CRH), which stimulates the anterior RECEPTOR CONTROL CENTER pituitary to release 3 2 Hypothalamus 3 The hypothalamus adrenocorticotropic CRH responds to various releases corticotropin- hormone (ACTH). stimuli. releasing hormone ACTH stimulates the (CRH) into the adrenal cortex to release hypothalamo-hypophyseal cortisol. This portal system. NEGATIVE FEEDBACK physiologic relationship is referred to as the 8 Cortisol levels increase, 4 In response to CRH, the anterior pituitary inhibiting release of CRH 4 ACTH releases adrenocorticotropic hormone hypothalamic-pituitary- and ACTH. adrenal axis. Cortisol (ACTH). increases the 5 ACTH stimulates the adrenal cortex to availability of nutrient release glucocorticoids (e.g., cortisol) molecules to support into the blood. the response to stress. NET EFFECT 6 Cortisol stimulates target cells (effectors). (Direction of arrows 7 Increase all nutrient levels between the blood and in blood. effectors indicates the net movement of the 5 Cortisol Blood vessel nutrients.) Amino acids Glucose Amino acids Cortisol bound by carrier proteins Glycerol fatty acids (e.g., CBG) 6 EFFECTORS: Effectors respond to cortisol in the following ways: Liver Adipose connective All cells High levels of cortisol: tissue Increase retention of Na+, H2O Decrease inflammation Suppress the immune system Inhibit connective tissue repair Increased glycogenolysis Increased lipolysis Stimulation of protein catabolism and gluconeogenesis Decreased lipogenesis (occurs in all cells except hepatocytes) Decreased glycogenesis Decreased glucose uptake Chapter Seventeen Endocrine System 681  Cortisol release fluctuates based on the time of day (circadian rhythm). Cortisol level is increased by stress. 24 hours 150 Percent deviation from the mean Sleep 100 50 0 –50 –100 0 8 16 24 Hours (a) (b) Figure 17.20 Variables That Influence Blood Levels of Cortisol. Blood levels of cortisol (a) fluctuate throughout the day and (b) rise with increased stress, which is why cortisol is sometimes called the “stress hormone.” Cortisol circulates in the blood, and small amounts become unbound (in addition to blood levels of cortisol) influence the release of CRH from their carrier protein and exit the blood. from the hypothalamus. These stimuli include (as measured by cortisol The release of both CRH from the hypothalamus and ACTH from hormone levels in the blood) (figure 17.20): the anterior pituitary (steps 3 and 4) is regulated by negative feedback (step 8). Increasing levels of cortisol inhibit the release of CRH from ∙∙ Time of Day. There are daily fluctuations in the release of the hypothalamus and ACTH from the anterior pituitary. Other factors cortisol. Notice in figure 17.20a that in a normal sleep-wake INTEGRATE CLINICAL VIEW 17.6 diseases such as rheumatoid arthritis, although some cases result when the adrenal gland produces too much of its own glucocorticoid hormones. Disorders in Adrenal Cortex Corticosteroids are powerful immunosuppressant drugs, but they have serious Hormone Secretion side effects, such as osteoporosis, muscle weakness, redistribution of body fat, and salt retention (resulting in overall swelling of the tissues). Cushing syndrome Three abnormal patterns of adrenal cortical function are Cushing syndrome, is characterized by body obesity, especially in the face (called moon face) and Addison disease, and androgenital syndrome. back (buffalo hump). Other symptoms include hypertension, hirsuitism (excess Cushing syndrome results from the chronic exposure of the body’s tissues male-pattern hair growth), kidney stones, and menstrual irregularities. to excessive levels of glucocorticoid hormones. This complex of symptoms is seen Addison disease (previously termed Addison's disease) involves insufficient most frequently in people taking corticosteroids as therapy for autoimmune production of steroids (usually glucocorticoids and perhaps mineralocorticoids) from the adrenal cortex. Addison disease can result from (a) adrenal glands that were malformed during development, (b) impaired enzymatic pathways for steroid synthesis, and (c) destruction of the adrenal gland (typically by an autoimmune disorder that forms autoantibodies against the adrenal gland that results in its destruction). The symptoms include weight loss, general fatigue and weakness, hypotension, and darkening of the skin. Perhaps the best-known person with Addison disease was John Fitzgerald Kennedy (JFK), 35th president of the United States. Adrenogenital syndrome, or congenital adrenal hyperplasia, first manifests in the embryo and fetus. It is characterized by the inability to synthesize corticosteroids. The anterior pituitary, sensing the deficiency of corticosteroids, releases massive amounts of ACTH in an unsuccessful effort to bring the glucocorticoid content of the blood up to a healthy level. This large amount of ACTH produces hyperplasia (increased size) of the adrenal cortex and causes the release of intermediary hormones that have a testosterone-like effect. The result is virilization (masculinization) in a newborn. Virilization in Photo prior to onset of Symptoms resulting from the females means the clitoris is enlarged, sometimes to the size of a male penis. Cushing syndrome. excessive glucocorticoid The effect may be so profound that the sex of a newborn genetic female is Courtesy of the Cushing’s Support and secretion in Cushing syndrome questioned or even mistaken. A virilized male may have an enlarged penis and Research Foundation, www.CSRF.net and Kathy Carbone include moon face. exhibit signs of premature puberty as early as age 6 or 7. (See Clinical View 28.12: Courtesy of the Cushing's Support and Research Foundation, www.CSRF.net and Kathy Carbone “Intersex Conditions (Disorders of Sex Development)” for additional details.) 682 Chapter Seventeen Endocrine System  cycle, peak levels of cortisol correspond to the late stages of a also function in converting some cortisol to c­ ortisone; a function not normal sleep cycle. About half of all cortisol release occurs shown in figure 17.19.) when you are asleep, with cortisol levels peaking right before Adipose connective tissue cells are stimulated by cortisol to waking in the morning. This rhythm of release is regulated by increase lipolysis and decrease lipogenesis (see section 2.7b), resulting light and dark cycles detected by the retina as nerve signals are in the release of glycerol and fatty acids into blood. This provides alter- relayed to the hypothalamus. (There is significant variation in native nutrients for gluconeogenesis. normal levels of cortisol in individuals.) Most cells, including muscle cells, skin cells, and bone cells, ∙∙ Stress. Both emotional stress (e.g., anxiety, anger, fear) and increase protein catabolism (breakdown of protein into amino acids) physical stress (e.g., fever, trauma, intense exercise) increase the in response to cortisol. An exception to this occurs in hepatocytes. release of cortisol (figure 17.20b). The influence of chronic In liver cells, additional amino acid released into the blood provides stress in triggering increased cortisol levels in the blood is the alternative nutrient molecules for gluconeogenesis. Cortisol addition- reason that cortisol has been given the nickname “the stress ally stimulates most cells to decrease glucose uptake. This is the hormone” (see Clinical View 17.7: “The Stress Response”). glucose-sparing effect, which saves blood glucose for use in the brain. The details for cortisol are listed in the summary table, Effects of Cortisol in the reference section, on regulating the stress response, which Cortisol and corticosterone are lipid-soluble hormones that increase directly follows this chapter (see table R.5). nutrient levels in the blood (glucose, fatty acids, and amino acids), espe- cially in an attempt to resist stress and help repair injured or damaged tissues. Other physiologic changes are stimulated by glucocorticoids Therapeutic Doses of Corticosterone and become most evident when present in high doses (steps 6 and 7). Corticosterone often is used as a treatment for chronic inflammation Cortisol specifically stimulates hepatocytes to increase and selected allergic reactions (e.g., hives, eczema). The side effects glycogenolysis and gluconeogenesis and decrease glycogenesis (see of corticosterone, especially when administered in high doses, section 2.7c).Consequently, blood glucose levels rise. (Hepatocytes include retention of Na+ and water; inhibited release of inflammatory INTEGRATE CLINICAL VIEW 17.7 The Stage of Resistance The Stress Response The stage of resistance occurs after a (General Adaptation Syndrome) few hours as glycogen stores in the liver are depleted. This stage is Stressors may fall under the category of either emotional stress (e.g., anxiety, regulated p­rimarily by the anger, fear, excitement) or physical stress (e.g., fever, trauma, hemorrhage, endocrine system. The major surgery, malnutrition). Stressors elicit the stress response (or general adaptation changes are induced by the syndrome), which was defined by Hans Selye (a pioneer in the endocrinology of release of glucocorticoids stress) as “the nonspecific response of the body to any demand made upon it.” (e.g., cortisol). The principal The body’s response to stress is initiated by the hypothalamus and involves both function of this stage is to the nervous system and the endocrine system. In 1936, Hans Selye described the provide glucose to meet the response to stressors in three stages: the alarm reaction, the stage of resistance, increased energy demands. and the stage of exhaustion. Glucose is especially important for nervous tissue The Alarm Reaction because it is the main nutrient The alarm reaction is the initial reaction to stress and is regulated primarily by the molecule for cellular respiration. sympathetic division of the autonomic nervous system (see section 15.4a). The To meet the increased demands hypothalamus activates the sympathetic division with subsequent stimulation of fStop/Getty Images for energy, gluconeogenesis is the adrenal medulla to release epinephrine and norepinephrine into the blood. The increased in the liver, and glucose is released into the blood. Glycerol and fatty acids following changes occur to the body (see section 15.4c): increase in the blood due to increased lipolysis in adipose connective tissue cells. ∙∙ Pupils dilate. Amino acids increase as a result of increased protein catabolism (and decreased ∙∙ Bronchioles dilate. protein synthesis) in most cells. Glycerol and amino acids provide the liver with ∙∙ Respiration rate increases. alternative nutrients for gluconeogenesis. Additionally, glucose uptake is inhibited in most cells. The net result is elevated blood glucose levels. ∙∙ Blood pressure increases as: ∙ Cardiac output increases The Stage of Exhaustion ∙ Blood vessels vasoconstrict The stage of exhaustion occurs after weeks or months, as fat stores in adipose ∙ Blood volume increases (with sodium and water retention) connective tissue are depleted. With fat stores depleted, and as structural proteins of the body’s cells continue to be broken down for gluconeogenesis, ∙∙ Potassium and hydrogen ions are excreted. the body becomes progressively weaker. Additionally, elevated levels of ∙∙ Both glucose and lipid levels in the blood increase. aldosterone may cause fluid, electrolyte, and pH imbalances. The combination ∙∙ Sweating increases. of body weakness, electrolyte imbalances, and other factors may ultimately ∙∙ Both digestion and urine production activities decrease. cause organ failure and death. Chapter Seventeen Endocrine System 683 agents (the anti-inflammatory effect); suppression of the immune acinus; grape). Each is specifically called a pancreatic acinus. The system; and inhibited connective tissue repair. Note that suppression pancreatic acini serve as an exocrine gland by producing digestive of the immune system increases an individual’s susceptibility to enzymes, which are released into the pancreatic ducts and ultimately infection and risk of cancer. into the duodenum region of the small intestine (see section 26.3c). The endocrine cells of the pancreas are located within small clusters called pancreatic islets (ī′let), also known as islets of WHAT DID YOU LEARN? Langerhans. These endocrine cell clusters form only about 1% of the 26 What is the relationship of CRH, ACTH, and cortisol? total pancreatic volume. A pancreatic islet is composed of two pri- 27 What are the primary target organs and tissues of cortisol? Describe the mary types of cells: alpha cells, which secrete glucagon (glū′kă-gon), effect on each. and beta cells, which secrete insulin (in′sū-lin; insula = island). Minor cells within the pancreatic islets include delta cells, which secrete somatostatin (also named growth hormone–inhibiting 17.10 The Pancreas hormone), and F cells, which secrete pancreatic polypeptide. These minor cells and their hormones will not be discussed further. The pancreas releases both insulin and glucagon. We first describe the anatomy of the pancreas and then discuss the regulation of insulin and glucagon and the effects of each hormone on its target organs. WHAT DID YOU LEARN? 28 Why is the pancreas considered both an exocrine gland and an endocrine gland? 17.10a Anatomy of the Pancreas LEARNING OBJECTIVES INTEGRATE 32. Identify and describe the gross anatomy and cellular structure of the pancreas. 33. Compare and contrast the primary types of pancreatic islet cells and the CONCEPT CONNECTION hormones they produce. The pancreas is unusual in that it functions as both an endocrine gland and an The pancreas (pan′krē-as; pan = all, kreas = flesh) is an elongated exocrine gland (see section 5.1d). Endocrine glands release their secretions organ situated between the duodenum of the small intestine and the (hormones) into the blood. The pancreas releases both insulin and glucagon into spleen, and posterior to the stomach (figure 17.21). The vast major- the blood. In contrast, exocrine glands release their secretions into ducts. The ity of the cells of the pancreas (about 99%) serve an exocrine gland pancreas also releases pancreatic juice containing digestive enzymes into ducts function. These cells, specifically called acinar cells, are modified that empty into the small intestine (duodenum), as described in section 26.3c. simple cuboidal epithelial cells arranged in saclike acini (sing., Abdominal Body of Spleen Blood capillary aorta pancreas Inferior Pancreatic islet vena cava Alpha cell Beta cell Bile Delta cell duct F cell Pancreatic acinus Pancreatic ducts Tail of pancreas Pancreatic Duodenum acinus of small intestine Head of Pancreatic pancreas islet (a) Anterior view Figure 17.21 Pancreas. The pancreas performs both exocrine and endocrine activities. (a) An illustration shows the relationship between the pancreas and both the duodenum (first section of the small intestine) and the spleen. (b) A diagram and micrograph reveal the histology LM 100x of a pancreatic islet. Four types of islet cells are shown in the diagram, including alpha cells that release glucagon and beta cells that release insulin. (b) ©Ed Reschke/Getty Images (b) Microscopic view of the pancreas 684 Chapter Seventeen Endocrine System 17.10b Pancreatic Hormones Lowering High Blood Glucose Levels with Insulin This section provides a detailed examination of the homeostatic sys- LEARNING OBJECTIVES tem involving insulin. We describe its regulated release by the pan- 34. Describe the action of insulin in lowering blood glucose concentration. creas and its effects (as a water-soluble hormone) on its target cells. 35. Explain the action of glucagon in raising blood glucose concentration. Please refer to figure 17.22, as you read through this section and note that each of the indicated steps are illustrated in this figure. Chemoreceptors in the beta cells of the pancreas detect an increase The primary endocrine function of the pancreas is to maintain the in blood glucose (readings greater than the normal 70–110 mg/dL) and concentration of glucose in the blood within a normal range of 70 are stimulated to release insulin (a protein hormone) into the blood to 110 milligrams of glucose per deciliter (mg/dL; a deciliter is an (steps 1–3). Target cells bind insulin, which activates second messen- amount equivalent to 100 milliliters). Chronically high blood glu- gers within the target cell. (Additionally, recent evidence suggests that cose levels can be very damaging to blood vessels and the kid- insulin may also enter the cell and directly bind to intracellular recep- neys, so this excess glucose must be transported into other body tors.) Insulin’s effects are as follows (step 4): cells that can use or store this resource. Conversely, low blood glucose levels result in lethargy, impairment of mental and physi- ∙∙ Glycogenesis (see section 2.7c) in hepatocytes is stimulated, cal function, and death if glucose levels drop too low. Thus, blood and both glycogenolysis and gluconeogenesis are inhibited, glucose levels must be closely regulated. The homeostatic mecha- resulting in glucose molecules being removed from the blood nisms for insulin and glucagon are described next and are sum- and stored as glycogen within liver cells. marized in the reference section table, which directly follows this ∙∙ Lipogenesis (see section 2.7b) in adipose connective tissue cells chapter (see table R.1). is stimulated, and lipolysis is inhibited. Fatty acid levels in the blood decrease, and the storage of fat is increased as a result. Insulin Pancreas Stimulation STIMULUS Inhibition 1 Blood glucose levels increase. RECEPTOR CONTROL CENTER 1 2 2 Beta cells within the 3 Beta cells release pancreas detect insulin. increased in blood NET EFFECT glucose levels. 3 Insulin 6 Negative feedback 5 Blood glucose (and other Insulin release is nutrient) levels decrease. inhibited as blood 4 Insulin stimulates target glucose levels cells (effectors). decrease to normal. Blood vessel Glucose Gllu G Glu l cos cose co Glucose Amino acids Fatty acids Insulin 4 EFFECTORS: Effectors respond to insulin in the following ways: Liver tissue Adipose connective tissue All cells Most cells (especially muscle) Increased uptake of Increased glycogenesis Increased lipogenesis Increased uptake glucose by increasing of amino acids, which glucose transport Decreased glycogenolysis Decreased lipolysis stimulates protein proteins in the plasma and gluconeogenesis anabolism membrane Figure 17.22 Regulation and Action of Insulin. Insulin is released from beta cells within pancreatic islets in response to high blood glucose. Insulin decreases the level of all nutrient molecules (glucose, fatty acids, and amino acids) within the blood. The uptake of fatty acids and amino acids from the blood limits their availability, making it more likely that cells will use glucose available within the blood as their nutrient molecule for cell respiration. Thus, blood glucose more quickly returns to within normal homeostatic levels. Chapter Seventeen Endocrine System 685  ∙∙ Most cells are stimulated to increase their cellular uptake of WHAT DO YOU THINK? (a) amino acids (especially muscle cells), a change that induces 8 Bodybuilders have been known to inject insulin to increase muscle bulk. cells to increase protein anabolism (synthesis of amino acids Explain their reasoning. What is the risk of an insulin overdose? into protein); and (b) glucose, especially by the cells of muscle and adipose connective tissue. The uptake of glucose occurs as Raising Low Blood Glucose Levels with Glucagon intracellular vesicles containing glucose transport proteins All nervous tissue depends almost exclusively upon glucose for cel- (­specifically, Glut4 transport proteins) fuse with the plasma lular respiration. To prevent impairment of mental function, ­lethargy, membrane. Additional glucose transport proteins are placed and possibly death, blood glucose levels must be prevented from within the plasma membrane of cells, providing the glucose dropping too low. Glucagon is one of the important hormones ­carrier molecules needed to bring more glucose into the cell. released in response to low blood glucose levels. This section pro- (These carriers are later removed as insulin levels decrease.) vides a detailed examination of the homeostatic system involving In summary, the net effect from the release of insulin is a decrease in glucagon. We describe its regulated release by the pancreas and its blood levels of glucose, as well as other nutrient molecules (step 5). By effects (as a water-soluble hormone) on its target cells. Please refer to decreasing alternative nutrients (fatty acids and amino acids), the cells figure 17.23 as you read through this section and note that each of of the body are more likely to use the available glucose within the blood the indicated steps are illustrated in this figure. and help return blood glucose to a normal level more quickly. The release Chemoreceptors in the alpha cells of the pancreas detect decreased of insulin is controlled by negative feedback (step 6); as blood glucose blood glucose levels and subsequently release glucagon (a protein levels decrease, less insulin is released from the pancreas. hormone) into the blood (steps 1–3). Glucagon binds to plasma mem- Note that some cells do not require insulin for glucose uptake. brane receptors to activate second messengers (cAMP) (see These cells include neurons, kidney cells, hepatocytes, and erythro- section 17.5b) that cause the following (step 4): cytes (red blood cells). Each of these cells takes up glucose indepen- ∙∙ Glycogenolysis and gluconeogenesis (see section 2.7c) in dently without external stimulation. ­hepatocytes are stimulated, and glycogenesis is inhibited; ­glucose is released into the blood, thereby increasing blood glucose INTEGRATE CLINICAL VIEW 17.8 who has a genetic predisposition, although some kind of triggering event is required to start the process. Often, the trigger is a viral infection leading to an Conditions Resulting in Abnormal autoimmune condition in which the beta cells of the pancreatic islets are destroyed. Blood Glucose Levels Treatment of type 1 diabetes requires regular injections of insulin. The recent use of stem cells shows promise as an effective means in treating type 1 diabetes. Type 2 diabetes, also known as insulin-independent diabetes mellitus (IIDM), Diabetes Mellitus results from either decreased insulin release from the beta cells of the pancreatic Diabetes mellitus (dí-ă-bē΄tez = a siphon, me-lī΄tŭs = sweetened with honey) islets or decreased insulin effectiveness on target cells at peripheral tissues. This is a metabolic condition marked by an increase in blood glucose. The name is type of diabetes was previously referred to as adult-onset diabetes because it derived from the phrase sweet urine because some of the excess glucose may tended to occur in people over the age of 30. However, type 2 diabetes is now be filtered into the urine, a condition called glucosuria. Chronically elevated blood often found in adolescents and young adults. Obesity plays a major role in the glucose levels damage blood vessels, especially the smaller arterioles. Because development of type 2 diabetes, and more young people are overweight than in of its damaging effects on the vascular system, diabetes is the leading cause of the past. Most patients with type 2 diabetes can be successfully treated with a retinal blindness, kidney failure, and nontraumatic leg amputations in the United combination of diet, exercise, and medications that enhance insulin release or States. Diabetes is also associated with increased incidence of heart disease and increase sensitivity to insulin at the tissue level. A person with type 2 diabetes stroke. must take insulin injections in more severe cases. Measuring the amount of glucose attached to hemoglobin molecules within Gestational diabetes is seen in some pregnant women, typically in the latter erythrocytes (hemoglobin A1C test) is an accurate means for determining the half of the pregnancy. If untreated, gestational diabetes can pose a risk to the degree of risk for an individual. The greater the amount of attached fetus as well as increase delivery complications. For further information, see glucose, the higher the risk of developing diabetes. The three Clinical View 29.4: “Gestational Diabetes.” classic signs of diabetes are (a) increased hunger (polyphagia) because the cells are unable to normally absorb the glucose Hypoglycemia from the blood into their cells and the cells lack sufficient Hypoglycemia occurs when blood glucose levels drop below 60 mg/dL. energy, (b) increased urination (polyuria) because glucose Hypoglycemia is not a disease; however, it may be a nonspecific indicator of some lost in the urine acts to pull fluid into the urine by osmosis, underlying homeostatic imbalance. The causes of hypoglycemia are numerous and (c) increased thirst (polydipsia) because of the abnormal and include insulin overdose, prolonged and intense exercise, alcohol consumption loss of fluid in the urine and the body is dehydrated. on an empty stomach, liver or kidney dysfunction, deficiency of either Three categories of diabetes mellitus are type 1 glucocorticoids or growth hormone, and certain genetic conditions. Symptoms diabetes, type 2 diabetes, and gestational diabetes. may include hunger, dizziness, nervousness, confusion, feeling anxious or weak, Type 1 diabetes is also referred to as insulin-dependent sweating, sleepiness, or any combination of these. The symptoms are thought to diabetes mellitus (IDDM) or juvenile diabetes. It is characterized occur from insufficient glucose to the brain or from the activation of the Individual injecting by absent or diminished production and release of insulin by sympathetic nervous system in response to low blood glucose levels. insulin in the the beta cells of the pancreatic islets. This type tends to occur If an individual is unable to eat or drink safely, such as if unconscious, subcutaneous layer. ©Ian Hooton/SPL/ in children and younger individuals, and is not directly unresponsive, or having convulsions, glucagon can be administered by injection. Getty Images associated with obesity. Type 1 diabetes may develop in a person This provides a safe means to offset the low blood glucose level. 686 Chapter Seventeen Endocrine System  Glucagon Pancreas Stimulation STIMULUS Inhibition 1 Blood glucose levels decrease. 1 2 RECEPTOR CONTROL CENTER 2 Alpha cells within the 3 Alpha cells within NET EFFECT pancreas detect a the pancreas 6 Negative feedback decrease in blood release glucagon. Glucagon release is glucose levels. 5 Blood glucose and glycerol and inhibited as blood fatty acid levels glucose levels 3 Glucagon increase. increase to normal. 4 Glucagon stimulates target cells (effectors). Blood vessel Glycerol fatty acids Glucose Glucagon 4 EFFECTORS: Effectors respond to glucagon in the following ways: Liver Adipose connective tissue Increased glycogenolysis Increased lipolysis and gluconeogenesis Decreased lipogenesis Decreased glycogenesis Figure 17.23 Regulation and Action of Glucagon. Glucagon is released from alpha cells within pancreatic islets in response to low blood glucose levels. Glucagon binds with target cells that increase glucose, glycerol, and fatty acid levels within the blood. l­evels. (Glucose within muscle cells is not released but remains 30 What are the stimulus, receptor, control center, and effector response to within muscle cells and is oxidized in cellular respiration.) the release of insulin? Indicate what happens to nutrient levels in the blood. ∙∙ Lipolysis (see section 2.7b) in adipose connective tissue cells is 31 Which of these hormones causes release of glucose into the blood: stimulated, and lipogenesis is inhibited. Fatty acids and g­ lycerol growth hormone, thyroid hormone, cortisol, insulin, or glucagon? are released from fat storage and are increased within the blood. In summary, the net effect of glucagon is an increase in glucose, glycerol, and fatty acids in the blood (step 5). The release of glucagon is controlled by negative feedback (step 6); as blood glucose levels 17.11 Other Endocrine Glands increase, less glucagon is released from the pancreas. Here we describe other endocrine glands and the functions of the Note that glucagon has no effect on the structural and functional hormones that are released by each. protein components of the body. The physiologic significance of this lack of effect is that the ongoing, and regular, release of this hormone 17.11a Pineal Gland (e.g., during periods between meals) does not tear down the muscles and other protein components of the body to maintain blood glucose LEARNING OBJECTIVE levels in “nonemergency” situations. 36. Describe the general structure, location, and function of the pineal gland. Note that paramedics may administer glucagon subcutaneously in certain conditions when low blood glucose is detected. This may be The pineal (pin′ē-ăl) gland (or pineal body) is a small, cone-shaped done if the individual is unconscious and is unable to be given sugar structure forming the posterior region of the epithalamus within the orally to directly raise blood glucose. diencephalon (see figure 17.2 and section 13.4a). The pineal gland secretes melatonin (mel-ă-tōn′in; melas = dark hue, ton as = contrac- WHAT DID YOU LEARN? tion), which makes us drowsy. Melatonin production tends to be cyclic; 29 Is the stimulus for insulin and glucagon release from the pancreas it increases at night, decreases during the day, and has the lowest hormonal, humoral, or nervous? levels around lunchtime. Melatonin helps regulate the circadian rhythm Chapter Seventeen Endocrine System 687 (24-hour body clock). Studies have linked irregular levels of melatonin Heart with mood (affective) disorders, such as seasonal affective disorder Endocrine cells within the atria of the heart synthesize and release the (SAD). Patients suffering from SAD may be treated with special light hormone atrial ­natriuretic (nā′trē-yū-ret′ik; natrium = to carry, ouron therapy that helps suppress melatonin secretion. = urine) peptide (ANP) in response to increased stretch of the atrial Melatonin also appears to affect the synthesis of gonadotropin- wall (which indicates an increase in blood volume and blood pressure). releasing hormone (GnRH) from the hypothalamus. This hormone is This peptide hormone stimulates both the kidneys to increase urine responsible for regulating the synthesis of follicle-stimulating hormone output (which decreases blood volume) and the blood vessels to dilate. (FSH) and luteinizing hormone (LH) from the anterior pituitary, which Both of these actions facilitate blood pressure to decrease and return it in turn regulate the reproductive system. The role of melatonin in to within normal homeostatic limits. Thus, the primary function of ANP sexual maturation is not well understood. However, excessive melatonin is to lower blood pressure. The functional details of ANP are described secretion is known to delay puberty in humans. in sections 24.5e, 24.6d, and 25.4d and summarized in the reference tables following this chapter (see table R.7). WHAT DID YOU LEARN? 32 How do melatonin levels change throughout the day? Kidneys Endocrine cells within the kidneys release erythropoietin (EPO) 17.11b Parathyroid Glands (ĕ-rith′rō-poy′ĕ-tin) when specialized receptors (chemoreceptors) with- in the kidney detect low blood oxygen levels. EPO stimulates red bone LEARNING OBJECTIVE marrow to increase the production rate of red blood cells (erythrocytes), 37. Describe the general structure, location, and function of the para­thyroid which are the oxygen-carrying cells. The functional details of erythro- glands. poietin are described in section 18.3b and summarized in the reference tables following this chapter (see table R.6). The small, brownish-red parathyroid (par-ā-thī′royd) glands are located on the posterior surface of the thyroid gland (see figure 17.2). These Liver glands are usually four small nodules, but some individuals may have as Recall that the liver releases insulin-like growth factors (IGFs) in few as two or as many as six of these glands. There are two different response to growth hormone, as described in section 17.7d. The liver types of cells in the parathyroid glands: chief cells and oxyphil cells. also ­releases angiotensinogen (an′jē-ō-ten-sin′ō-jen), an inactive The more common chief cells, or principal cells, are the source hormone. The activation of angiotensinogen to angiotensin II (the of parathyroid hormone (PTH), which is released from the parathy- active form of the hormone) requires both an enzyme released from roid gland in response to a decrease in blood calcium levels. Parathy- the kidney (renin) and an enzyme anchored within the inner lining of roid hormone increases blood calcium levels by stimulating release blood vessels (­angiotensin-converting enzyme, or ACE) (see Clinical of calcium from bone tissue, decreasing loss of calcium in urine, and View 25.5: “Angiotensin-Converting Enzyme (ACE) Inhibitors”). causing the kidney to release an enzyme to convert the inactive cal- The primary function of angiotensin II is to increase blood pressure. cidiol hormone to the active calcitriol hormone (see section 17.11c). ­Angiotensin II has several effects. It (a) is a powerful blood vessel The functional details of PTH and calcitriol are described in constrictor, (b) stimulates the kidney to decrease urine output, and section 7.6b and summarized in the reference tables following this (c) stimulates the thirst center in the hypothalamus. All of these pro- chapter (see table R.2). (See Clinical View 7.6: “Rickets” and cesses function to keep blood pressure within normal homeostatic Clinical View 7.7: “Osteoporosis.”) limits. (Note: The liver also secretes EPO; however, the primary The role of oxyphil cells is not known, although these cells are producers of EPO are the kidneys.) The functional details of associated with a rare form of cancer called oxyphil cell adenoma. angiotensin II are described in sections 20.6b, 24.5e, and 25.4a and summarized in the reference tables following this chapter (see WHAT DID YOU LEARN? table R.7). 33 What is the primary hormone released from the parathyroid gland? What is its general function? Stomach and Small Intestine The stomach and small intestine are regions of the gastrointestinal 17.11c Structures with an Endocrine Function (GI) tract. The stomach both synthesizes and releases gastrin (gas′trin; gaster = stomach), a hormone that acts primarily to LEARNING OBJECTIVE increase stomach activity (both its motility and its release of secre- 38. Identify and provide a description of the general function of the hormone(s) tions) to facilitate digestion within the stomach (see section 26.2d). released from each of the organs discussed in this section. The small intestine is a long tube that is inferior to the stomach and located medially within the abdominal cavity. The small intestine Thymus releases both secretin and cholecystokinin, both of which function to The thymus (thī′mŭs) is a bilobed organ that is located anterior to the facilitate digestion within the small intestine. A primary function of heart on its superior aspect (see figure 17.2). The thymus is relatively ­secretin (se-krē′tin) is to stimulate release of secretions from both the large in infants, continues to grow until puberty, and then begins to liver (bile) and pancreas (pancreatic juice) into the small intestine. A regress (decrease in size) after puberty. A connective tissue frame- primary function of cholecystokinin (CCK) (ko′lē-sis-to-kī′nin; work houses both epithelial cells and maturing ­ T-lymphocytes chole = bile, cyst = sac, kinin = to move), and what gives the hor- (a specific type of white blood cell). Immature T ­ -lymphocytes (thy- mone its name, is to stimulate release of bile from the ­gallbladder (a mocytes) migrate to the thymus following their formation in the bone muscular sac on the inferior surface of the liver). The f­unctional marrow, and epithelial cells there secrete thymic hormones (i.e., details of gastrin, secretin, and cholecystokinin are described in sec- thymosin, ­thymulin, and thymopoietin), which participate in the tions 26.2d and 26.3c and summarized in the reference tables follow- maturation of ­T-lymphocytes (see sections 21.3b and 22.5). ing this chapter (see table R.8). 688 Chapter Seventeen Endocrine System Skin following this chapter. They are organized based on their function (e.g., Ultraviolet light penetrates into surface skin cells (keratinocytes) to regulate blood glucose, regulate blood calcium). Each table includes convert modified cholesterol molecules to vitamin D3 (cholecalcifer- the chemical structure of the hormone, the endocrine gland that pro- ol), which is then released into the blood. Vitamin D3 is converted to duces it, the primary stimulus for its release, its primary target organs, calcidiol by an enzyme within the liver and then by an enzyme within and the cellular changes that it induces. In addition, the net result of the the kidney to calcitriol, the active hormone (which is a lipid-soluble hormone action, an example of a related disease or condition, and the sterol hormone). Calcitriol is similar to parathyroid hormone because section(s) in the text where it is described in detail are also included. it increases blood calcium by stimulating release of calcium from bone tissue and decreases c­ alcium loss in the urine. Additionally, calcitriol WHAT DID YOU LEARN? enhances the absorption of calcium from the contents of our digested 34 What is the function of the kidney in regulating erythrocyte concentration food within the lumen of the small intestine. Calcitriol stimulates epi- within the blood? thelial cells lining the small intestine to increase the number of plasma 35 What organ releases angiotensinogen, and what is the function of membrane Ca2+ transport proteins (e.g., calbinden). Without calcitriol, angiotensinogen following its activation? much of the calcium we ingest is not absorbed; it continues through the digestive tract and is lost in the feces. The functional details of c­ alcitriol are described in sections 6.1d and 7.6b, and summarized in the refer- 17.12 Aging and the Endocrine System ence tables following this chapter (see table R.2). LEARNING OBJECTIVE Adipose Connective Tissue 39. Describe how endocrine activity changes as people age. Adipose connective tissue is located throughout the body, and it releases the hormone leptin. This hormone helps to regulate food intake by bind- The secretory activity of endocrine glands typically wanes as we age. ing to the neurons within the hypothalamus that control appetite (see Aging reduces the efficiency of endocrine system functions, and often section 13.4c). Leptin stimulates down-regulation (see section 17.6a) of normal levels of hormones decrease. Many conditions experienced after other receptors for hormones that are involved in increasing appetite. middle age, such as abdominal weight gain or muscle loss, are directly Lower percentage of body fat is associated with lower blood levels of related to diminishing or reduced endocrine gland function. leptin, which stimulates the appetite. Thus, one of the functions of leptin One example is that the secretion of growth hormone (GH) typically is to regulate energy balance within the body. decreases. Reduction in GH levels leads to loss of weight and body mass Clinicians and researchers have become more aware of other in the elderly, although continued exercise reduces this effect. ­endocrine functions of adipose connective tissue by observing the In addition, testosterone and estrogen levels decline as males and outcomes of either excess or deficiency of this tissue. Excess adipose females age. A decrease in estrogen level after menopause contributes to connective tissue has been linked with various types of cancers (e.g., osteoporosis (see Clinical View 7.7: “Osteoporosis”). Hormone replace- colon, breast) and the delay of puberty in males, whereas abnormally ment therapy attempts to supplement sex hormone levels that have natu- low body fat can both delay the onset of puberty and interfere with a rally diminished with age. The benefits and side effects of hormone normal menstrual cycle in females. replacement therapy are discussed in greater detail in section 28.5f. Summary Tables WHAT DID YOU LEARN? The details of the major hormones discussed in this chapter (and 36 What general changes occur to the ability of endocrine glands to produce throughout the text) are summarized in tables that are located directly hormones as we age? CHAPTER SUMMARY ∙∙ The endocrine system is composed of endocrine glands that produce chemical communication molecules (ligands) called hormones. 17.1 Introduction ∙∙ The two control systems of the body include the endocrine system and nervous system. to the Endocrine System 17.1a Overview of the Endocrine System ∙∙ The endocrine system is composed of endocrine glands, which release hormones into the blood to control target cells. 17.1b Comparison of the Two Control Systems ∙∙ The endocrine and nervous systems complement each other to maintain homeostasis. 17.1c General Functions of the Endocrine System ∙∙ The primary processes controlled by hormones include regulating development, growth, and metabolism; maintaining homeostasis of blood composition and volume; controlling digestive processes; and controlling reproductive activities. 17.2 Endocrine ∙∙ Endocrine glands are located throughout the body and are regulated to secrete their hormones into the blood. Glands 17.2a Location of the Major Endocrine Glands ∙∙ Endocrine organs include the pituitary gland, pineal gland, thyroid gland, parathyroid glands, and adrenal glands. ∙∙ Endocrine tissue is housed in small clusters within the hypothalamus, skin, thymus, heart, liver, stomach, pancreas, small intestine, adipose connective tissue, kidneys, and gonads. 17.2b Stimulation of Hormone Synthesis and Release ∙∙ Release of hormones from endocrine cells is controlled through reflexes. There are three ways to stimulate these cells: (a) hormonal stimulation, (b) humoral stimulation by nutrients or ions in the blood, and (c) nervous system stimulation. (continued on next page) Chapter Seventeen Endocrine System 689  CHAPTER SUMMARY (continued) 17.3 Categories ∙∙ Hormones are categorized as circulating hormones or local hormones. of Hormones 17.3a Circulating Hormones ∙∙ Circulating hormones are either lipid-soluble (these include steroids, calcitriol, and thyroid hormone) or water-soluble (these include most biogenic amines and protein hormones that are synthesized from amino acids). 17.3b Local Hormones ∙∙ Eicosanoids are local hormones; they are synthesized from a fatty acid (arachidonic acid); following their formation, eicosanoids stimulate the cell that produced them (autocrine stimulation) or neighboring cells (paracrine stimulation). 17.4 Hormone ∙∙ The mechanism of hormone transport is dependent upon whether the hormone is lipid-soluble or water-soluble. Transport 17.4a Transport in the Blood ∙∙ Lipid-soluble hormones must attach to a carrier protein molecule to be transported within the blood. ∙∙ Water-soluble hormones readily dissolve in the aqueous environment of the blood and do not require a carrier protein. 17.4b Levels of Circulating Hormone ∙∙ The two primary factors that influence hormone concentration are hormone release by endocrine glands and hormone elimination by the liver, kidneys, and target cells. 17.5 Target Cells: ∙∙ Hormones bind with receptors of target cells; how this occurs is significantly different for lipid-soluble and water-soluble Interactions with hormones. Hormones 17.5a Lipid-Soluble Hormones ∙∙ Hormones that are lipid-soluble (steroids, calcitriol, and thyroid hormone) stimulate cellular activity by binding to intracellular receptors: The hormone-receptor complex activates a region of DNA, resulting in the production of new proteins. 17.5b Water-Soluble Hormones ∙∙ Hormones that are water-soluble (proteins and biogenic amines, except thyroid hormone) bind with plasma membrane receptors; the hormone is the first messenger, and it causes the activation of G protein and the formation of a second messenger through an intracellular enzyme cascade. ∙∙ The cellular response may include activation or inhibition of enzymatic pathways, stimulation of growth through cellular division, stimulation of cellular secretions, change in plasma membrane ion permeability, and muscle contraction or relaxation. 17.6 Target Cells: ∙∙ The degree of cellular response is a function of both its displayed receptors and the amounts and kinds of hormones Degree of that it binds. Cellular Response 17.6a Number of Receptors on a Target Cell ∙∙ Up-regulation is the increase in the number of receptors, and down-regulation is a decrease in the number of receptors. Being able to change receptor number allows a target cell to modify its responsiveness to a hormone. 17.6b Hormone Interactions on a Target Cell ∙∙ A single target cell may possess receptors for many different hormones. ∙∙ Multiple hormones may interact with target cells to have one of three effects: synergistic, permissive, or antagonist. 17.7 The ∙∙ The hypothalamus directly controls the release of hormones from the pituitary gland and, through its control of the anterior Hypothalamus pituitary, regulates the release of hormones from other endocrine glands. and the Pituitary 17.7a Anatomic Relationship of the Hypothalamus and the Pituitary Gland Gland ∙∙ The pituitary gland is inferior to the hypothalamus and connected to it by the infundibulum. ∙∙ The hypothalamus communicates with the posterior pituitary via the hypothalamo-hypophyseal tract, which contains axons from two nuclei in the hypothalamus: the supraoptic nucleus and the paraventricular nucleus. ∙∙ The hypothalamus communicates with the anterior pituitary via the hypothalamo-hypophyseal portal system, a blood vessel network that transports hormones from the hypothalamus to the anterior pituitary. 17.7b Interactions Between the Hypothalamus and the Posterior Pituitary Gland ∙∙ In response to nerve signals, the posterior pituitary releases antidiuretic hormone (ADH) or oxytocin (OT), wh