Two lateral lobes connected by median mass called isthmus Thyroid Gland Two lateral lobes connected by median mass called isthmus Composed of follicles that produce glycoprotein thyroglobulin Colloid (thyroglobulin + iodine) fills lumen of follicles and is precursor of thyroid hormone Parafollicular cells produce the hormone calcitonin © 2013 Pearson Education, Inc.

Figure 16.9 The thyroid gland. Hyoid bone Colloid-filled follicles Thyroid cartilage Epiglottis Follicular cells Superior thyroid artery Common carotid artery Inferior thyroid artery Isthmus of thyroid gland Trachea Left subclavian artery Left lateral lobe of thyroid gland Aorta Parafollicular cells Gross anatomy of the thyroid gland, anterior view Photomicrograph of thyroid gland follicles (145x) © 2013 Pearson Education, Inc.

Actually two related compounds Thyroid Hormone (TH) Actually two related compounds T4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atoms T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms Affects virtually every cell in body © 2013 Pearson Education, Inc.

Major metabolic hormone Thyroid Hormone Major metabolic hormone Increases metabolic rate and heat production (calorigenic effect) Regulation of tissue growth and development Development of skeletal and nervous systems Reproductive capabilities Maintenance of blood pressure © 2013 Pearson Education, Inc.

Synthesis of Thyroid Hormone Thyroid gland stores hormone extracellularly Thyroglobulin synthesized and discharged into follicle lumen Iodides (I–) actively taken into cell and released into lumen Iodide oxidized to iodine (I2), Iodine attaches to tyrosine, mediated by peroxidase enzymes © 2013 Pearson Education, Inc.

Synthesis of Thyroid Hormone Iodinated tyrosines link together to form T3 and T4 Colloid is endocytosed and combined with lysosome T3 and T4 are cleaved and diffuse into bloodstream © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 1 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Iodine is attached to tyrosine in colloid, forming DIT and MIT. 4 Golgi apparatus Rough ER Thyro- globulin colloid Iodine Iodide is oxidized to iodine. 3 DIT MIT Iodide (I−) Iodide (I–) is trapped (actively transported in). 2 T4 Iodinated tyrosines are linked together to form T3 and T4. 5 T3 Lysosome T4 Thyroglobulin colloid is endocytosed and combined with a lysosome. 6 T3 Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream. 7 T4 Colloid in lumen of follicle T3 To peripheral tissues © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 2 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Golgi apparatus Rough ER Colloid in lumen of follicle © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 3 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Golgi apparatus Rough ER Iodide (I−) Iodide (I–) is trapped (actively transported in). 2 Colloid in lumen of follicle © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 4 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Golgi apparatus Rough ER Iodine Iodide is oxidized to iodine. 3 Iodide (I−) Iodide (I–) is trapped (actively transported in). 2 Colloid in lumen of follicle © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 5 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Iodine is attached to tyrosine in colloid, forming DIT and MIT. 4 Golgi apparatus Rough ER Thyro- globulin colloid Iodine Iodide is oxidized to iodine. 3 DIT MIT Iodide (I−) Iodide (I–) is trapped (actively transported in). 2 Colloid in lumen of follicle © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 6 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Iodine is attached to tyrosine in colloid, forming DIT and MIT. 4 Golgi apparatus Rough ER Thyro- globulin colloid Iodine Iodide is oxidized to iodine. 3 DIT MIT Iodide (I−) Iodide (I–) is trapped (actively transported in). 2 T4 Iodinated tyrosines are linked together to form T3 and T4. 5 T3 Colloid in lumen of follicle © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 7 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Iodine is attached to tyrosine in colloid, forming DIT and MIT. 4 Golgi apparatus Rough ER Thyro- globulin colloid Iodine Iodide is oxidized to iodine. 3 DIT MIT Iodide (I−) Iodide (I–) is trapped (actively transported in). 2 T4 Iodinated tyrosines are linked together to form T3 and T4. 5 T3 Lysosome Thyroglobulin colloid is endocytosed and combined with a lysosome. 6 Colloid in lumen of follicle © 2013 Pearson Education, Inc.

Figure 16.10 Synthesis of thyroid hormone. Slide 8 Thyroid follicular cells Colloid Thyroglobulin is synthesized and discharged into the follicle lumen. 1 Tyrosines (part of thyroglobulin molecule) Capillary Iodine is attached to tyrosine in colloid, forming DIT and MIT. 4 Golgi apparatus Rough ER Thyro- globulin colloid Iodine Iodide is oxidized to iodine. 3 DIT MIT Iodide (I−) Iodide (I–) is trapped (actively transported in). 2 T4 Iodinated tyrosines are linked together to form T3 and T4. 5 T3 Lysosome T4 Thyroglobulin colloid is endocytosed and combined with a lysosome. 6 T3 Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream. 7 T4 Colloid in lumen of follicle T3 To peripheral tissues © 2013 Pearson Education, Inc.

Transport and Regulation of TH T4 and T3 transported by thyroxine-binding globulins (TBGs) Both bind to target receptors, but T3 is ten times more active than T4 Peripheral tissues convert T4 to T3 © 2013 Pearson Education, Inc.

Transport and Regulation of TH Negative feedback regulation of TH release Rising TH levels provide negative feedback inhibition on release of TSH Hypothalamic thyrotropin-releasing hormone (TRH) can overcome negative feedback during pregnancy or exposure to cold © 2013 Pearson Education, Inc.

Hypothalamus TRH Anterior pituitary TSH Thyroid gland Figure 16.8 Regulation of thyroid hormone secretion. Hypothalamus TRH Anterior pituitary TSH Thyroid gland Thyroid hormones Stimulates Target cells Inhibits © 2013 Pearson Education, Inc.

Homeostatic Imbalances of TH Hyposecretion in adults—myxedema; goiter if due to lack of iodine Hyposecretion in infants—cretinism Hypersecretion—Graves' disease © 2013 Pearson Education, Inc.

Figure 16.11 Thyroid disorders. © 2013 Pearson Education, Inc.

Produced by parafollicular (C) cells Calcitonin Produced by parafollicular (C) cells No known physiological role in humans Antagonist to parathyroid hormone (PTH) At higher than normal doses Inhibits osteoclast activity and release of Ca2+ from bone matrix Stimulates Ca2+ uptake and incorporation into bone matrix © 2013 Pearson Education, Inc.

Four to eight tiny glands embedded in posterior aspect of thyroid Parathyroid Glands Four to eight tiny glands embedded in posterior aspect of thyroid Contain oxyphil cells (function unknown) and parathyroid cells that secrete parathyroid hormone (PTH) or parathormone PTH—most important hormone in Ca2+ homeostasis © 2013 Pearson Education, Inc.

Capillary Parathyroid cells (secrete parathyroid hormone) Oxyphil Figure 16.12 The parathyroid glands. Pharynx (posterior aspect) Capillary Parathyroid cells (secrete parathyroid hormone) Thyroid gland Parathyroid glands Esophagus Oxyphil cells Trachea © 2013 Pearson Education, Inc.

Negative feedback control: rising Ca2+ in blood inhibits PTH release Parathyroid Hormone Functions Stimulates osteoclasts to digest bone matrix and release Ca2+ to blood Enhances reabsorption of Ca2+ and secretion of phosphate by kidneys Promotes activation of vitamin D (by kidneys); increases absorption of Ca2+ by intestinal mucosa Negative feedback control: rising Ca2+ in blood inhibits PTH release © 2013 Pearson Education, Inc.

Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine. Hypocalcemia (low blood Ca2+) PTH release from parathyroid gland Osteoclast activity in bone causes Ca2+ and PO43- release into blood Ca2+ reabsorption in kidney tubule Activation of vitamin D by kidney Ca2+ absorption from food in small intestine Ca2+ in blood Initial stimulus Physiological response Result © 2013 Pearson Education, Inc.

Homeostatic Imbalances of PTH Hyperparathyroidism due to tumor Bones soften and deform Elevated Ca2+ depresses nervous system and contributes to formation of kidney stones Hypoparathyroidism following gland trauma or removal or dietary magnesium deficiency Results in tetany, respiratory paralysis, and death © 2013 Pearson Education, Inc.

Adrenal (Suprarenal) Glands Paired, pyramid-shaped organs atop kidneys Structurally and functionally are two glands in one Adrenal medulla—nervous tissue; part of sympathetic nervous system Adrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroids © 2013 Pearson Education, Inc.

Three layers of cortex produce the different corticosteroids Adrenal Cortex Three layers of cortex produce the different corticosteroids Zona glomerulosa—mineralocorticoids Zona fasciculata—glucocorticoids Zona reticularis—gonadocorticoids © 2013 Pearson Education, Inc.

Figure 16.14 Microscopic structure of the adrenal gland. Hormones secreted Capsule Zona glomerulosa Aldosterone Zona fasciculata Adrenal gland • Medulla Cortex • Cortex Cortisol and androgens Kidney Zona reticularis Medulla Adrenal medulla Epinephrine and norepinephrine Drawing of the histology of the adrenal cortex and a portion of the adrenal medulla Photomicrograph (115x) © 2013 Pearson Education, Inc.

Regulate electrolytes (primarily Na+ and K+) in ECF Mineralocorticoids Regulate electrolytes (primarily Na+ and K+) in ECF Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions Importance of K+: sets RMP of cells Aldosterone most potent mineralocorticoid Stimulates Na+ reabsorption and water retention by kidneys; elimination of K+ © 2013 Pearson Education, Inc.

Aldosterone Release triggered by Decreasing blood volume and blood pressure Rising blood levels of K+ © 2013 Pearson Education, Inc.

Mechanisms of Aldosterone Secretion Renin-angiotensin-aldosterone mechanism: decreased blood pressure stimulates kidneys to release renin  triggers formation of angiotensin II, a potent stimulator of aldosterone release Plasma concentration of K+: increased K+ directly influences zona glomerulosa cells to release aldosterone ACTH: causes small increases of aldosterone during stress Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion to decrease blood pressure © 2013 Pearson Education, Inc.

water; increased K+ excretion Figure 16.15 Major mechanisms controlling aldosterone release from the adrenal cortex. Primary regulators Other factors Blood volume and/or blood pressure K+ in blood Stress Blood pressure and/or blood volume Hypo- thalamus Heart Kidney CRH Direct stimulating effect Anterior pituitary Renin Initiates cascade that produces ACTH Atrial natriuretic peptide (ANP) Angiotensin II Inhibitory effect Zona glomerulosa of adrenal cortex Enhanced secretion of aldosterone Targets kidney tubules Absorption of Na+ and water; increased K+ excretion Blood volume and/or blood pressure © 2013 Pearson Education, Inc.

Homeostatic Imbalances of Aldosterone Aldosteronism—hypersecretion due to adrenal tumors Hypertension and edema due to excessive Na+ Excretion of K+ leading to abnormal function of neurons and muscle © 2013 Pearson Education, Inc.

Keep blood glucose levels relatively constant Glucocorticoids Keep blood glucose levels relatively constant Maintain blood pressure by increasing action of vasoconstrictors Cortisol (hydrocortisone) Only one in significant amounts in humans Cortisone Corticosterone © 2013 Pearson Education, Inc.

Glucocorticoids: Cortisol Released in response to ACTH, patterns of eating and activity, and stress Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins Promotes rises in blood glucose, fatty acids, and amino acids "Saves" glucose for brain Enhances vasoconstriction  rise in blood pressure to quickly distribute nutrients to cells © 2013 Pearson Education, Inc.

Homeostatic Imbalances of Glucocorticoids Hypersecretion—Cushing's syndrome/disease Depresses cartilage and bone formation Inhibits inflammation Depresses immune system Disrupts cardiovascular, neural, and gastrointestinal function Hyposecretion—Addison's disease Also involves deficits in mineralocorticoids Decrease in glucose and Na+ levels Weight loss, severe dehydration, and hypotension © 2013 Pearson Education, Inc.

Same patient with Cushing’s syndrome. The white arrow shows Figure 16.16 The effects of excess glucocorticoid. Patient before onset. Same patient with Cushing’s syndrome. The white arrow shows the characteristic “buffalo hump” of fat on the upper back. © 2013 Pearson Education, Inc.

Gonadocorticoids (Sex Hormones) Most weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens May contribute to Onset of puberty Appearance of secondary sex characteristics Sex drive in women Estrogens in postmenopausal women © 2013 Pearson Education, Inc.

Gonadocorticoids Hypersecretion Adrenogenital syndrome (masculinization) Not noticeable in adult males Females and prepubertal males Boys – reproductive organs mature; secondary sex characteristics emerge early Females – beard, masculine pattern of body hair; clitoris resembles small penis © 2013 Pearson Education, Inc.

Adrenal Medulla Medullary chromaffin cells synthesize epinephrine (80%) and norepinephrine (20%) Effects Vasoconstriction Increased heart rate Increased blood glucose levels Blood diverted to brain, heart, and skeletal muscle © 2013 Pearson Education, Inc.

Adrenal Medulla Responses brief Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and heart Norepinephrine influences peripheral vasoconstriction and blood pressure © 2013 Pearson Education, Inc.

Adrenal Medulla Hypersecretion Hyposecretion Hyperglycemia, increased metabolic rate, rapid heartbeat and palpitations, hypertension, intense nervousness, sweating Hyposecretion Not problematic Adrenal catecholamines not essential to life © 2013 Pearson Education, Inc.

Figure 16.17 Stress and the adrenal gland. Short-term stress Prolonged stress Stress Nerve impulses Hypothalamus CRH (corticotropin- releasing hormone) Spinal cord Corticotropic cells of anterior pituitary Preganglionic sympathetic fibers To target in blood Adrenal cortex (secretes steroid hormones) Adrenal medulla (secretes amino acid– based hormones) ACTH Catecholamines (epinephrine and norepinephrine) Mineralocorticoids Glucocorticoids Short-term stress response Long-term stress response • Heart rate increases • Kidneys retain sodium and water • Proteins and fats converted to glucose or broken down for energy • Blood pressure increases • Bronchioles dilate • Blood volume and blood pressure rise • Liver converts glycogen to glucose and releases glucose to blood • Blood glucose increases • Immune system supressed • Blood flow changes, reducing digestive system activity and urine output • Metabolic rate increases © 2013 Pearson Education, Inc.

Pineal Gland Small gland hanging from roof of third ventricle Pinealocytes secrete melatonin, derived from serotonin Melatonin may affect Timing of sexual maturation and puberty Day/night cycles Physiological processes that show rhythmic variations (body temperature, sleep, appetite) Production of antioxidant and detoxification molecules in cells © 2013 Pearson Education, Inc.

Triangular gland partially behind stomach Pancreas Triangular gland partially behind stomach Has both exocrine and endocrine cells Acinar cells (exocrine) produce enzyme-rich juice for digestion Pancreatic islets (islets of Langerhans) contain endocrine cells Alpha () cells produce glucagon (hyperglycemic hormone) Beta () cells produce insulin (hypoglycemic hormone) © 2013 Pearson Education, Inc.

Pancreatic islet •  (Glucagon- producing) cells •  (Insulin- Figure 16.18 Photomicrograph of differentially stained pancreatic tissue. Pancreatic islet •  (Glucagon- producing) cells •  (Insulin- producing) cells Pancreatic acinar cells (exocrine) © 2013 Pearson Education, Inc.

Causes increased blood glucose levels Effects Glucagon Major target—liver Causes increased blood glucose levels Effects Glycogenolysis—breakdown of glycogen to glucose Gluconeogenesis—synthesis of glucose from lactic acid and noncarbohydrates Release of glucose to blood © 2013 Pearson Education, Inc.

Not needed for glucose uptake in liver, kidney or brain Insulin Effects of insulin Lowers blood glucose levels Enhances membrane transport of glucose into fat and muscle cells Inhibits glycogenolysis and gluconeogenesis Participates in neuronal development and learning and memory Not needed for glucose uptake in liver, kidney or brain © 2013 Pearson Education, Inc.

Insulin Action on Cells Activates tyrosine kinase enzyme receptor Cascade  increased glucose uptake Triggers enzymes to Catalyze oxidation of glucose for ATP production – first priority Polymerize glucose to form glycogen Convert glucose to fat (particularly in adipose tissue) © 2013 Pearson Education, Inc.

BALANCE: Normal blood glucose level (about 90 mg/100 ml) Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels. Stimulates glucose uptake by cells Insulin Tissue cells Stimulates glycogen formationw Pancreas Glucose Glycogen Blood glucose falls to normal range. Liver IMBALANCE Stimulus Blood glucose level BALANCE: Normal blood glucose level (about 90 mg/100 ml) Stimulus Blood glucose level IMBALANCE Blood glucose rises to normal range. Pancreas Glucose Glycogen Liver Stimulates glycogen breakdown Glucagon © 2013 Pearson Education, Inc.

Factors That Influence Insulin Release Elevated blood glucose levels – primary stimulus Rising blood levels of amino acids and fatty acids Release of acetylcholine by parasympathetic nerve fibers Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids Somatostatin; sympathetic nervous system © 2013 Pearson Education, Inc.

Homeostatic Imbalances of Insulin Diabetes mellitus (DM) Due to hyposecretion (type 1) or hypoactivity (type 2) of insulin Blood glucose levels remain high  nausea  higher blood glucose levels (fight or flight response) Glycosuria – glucose spilled into urine Fats used for cellular fuel  lipidemia; if severe  ketones (ketone bodies) from fatty acid metabolism  ketonuria and ketoacidosis Untreated ketoacidosis  hyperpnea; disrupted heart activity and O2 transport; depression of nervous system  coma and death possible © 2013 Pearson Education, Inc.

Diabetes Mellitus: Signs Three cardinal signs of DM Polyuria—huge urine output Glucose acts as osmotic diuretic Polydipsia—excessive thirst From water loss due to polyuria Polyphagia—excessive hunger and food consumption Cells cannot take up glucose; are "starving" © 2013 Pearson Education, Inc.

Homeostatic Imbalances of Insulin Hyperinsulinism: Excessive insulin secretion Causes hypoglycemia Low blood glucose levels Anxiety, nervousness, disorientation, unconsciousness, even death Treated by sugar ingestion © 2013 Pearson Education, Inc.

Table 16.4 Symptoms of Insulin Deficit (Diabetes Mellitus) © 2013 Pearson Education, Inc.

Ovaries and Placenta Gonads produce steroid sex hormones Same as those of adrenal cortex Ovaries produce estrogens and progesterone Estrogen Maturation of reproductive organs Appearance of secondary sexual characteristics With progesterone, causes breast development and cyclic changes in uterine mucosa Placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG) © 2013 Pearson Education, Inc.

Testes produce testosterone Initiates maturation of male reproductive organs Causes appearance of male secondary sexual characteristics and sex drive Necessary for normal sperm production Maintains reproductive organs in functional state © 2013 Pearson Education, Inc.

Other Hormone-producing Structures Adipose tissue Leptin – appetite control; stimulates increased energy expenditure Resistin – insulin antagonist Adiponectin – enhances sensitivity to insulin © 2013 Pearson Education, Inc.

Other Hormone-producing Structures Enteroendocrine cells of gastrointestinal tract Gastrin stimulates release of HCl Secretin stimulates liver and pancreas Cholecystokinin stimulates pancreas, gallbladder, and hepatopancreatic sphincter Serotonin acts as paracrine © 2013 Pearson Education, Inc.

Other Hormone-producing Structures Heart Atrial natriuretic peptide (ANP) decreases blood Na+ concentration, therefore blood pressure and blood volume Kidneys Erythropoietin signals production of red blood cells Renin initiates the renin-angiotensin-aldosterone mechanism © 2013 Pearson Education, Inc.

Other Hormone-producing Structures Skeleton (osteoblasts) Osteocalcin Prods pancreas to secrete more insulin; restricts fat storage; improves glucose handling; reduces body fat Activated by insulin Low levels of osteocalcin in type 2 diabetes – perhaps increasing levels may be new treatment Skin Cholecalciferol, precursor of vitamin D © 2013 Pearson Education, Inc.

Other Hormone-producing Structures Thymus Large in infants and children; shrinks as age Thymulin, thymopoietins, and thymosins May be involved in normal development of T lymphocytes in immune response Classified as hormones; act as paracrines © 2013 Pearson Education, Inc.

Developmental Aspects Hormone-producing glands arise from all three germ layers Most endocrine organs operate well until old age Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone function Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutants Interference with glucocorticoids may help explain high cancer rates in certain areas © 2013 Pearson Education, Inc.

Developmental Aspects Ovaries undergo significant changes with age and become unresponsive to gonadotropins; problems associated with estrogen deficiency occur Testosterone also diminishes with age, but effect is not usually seen until very old age © 2013 Pearson Education, Inc.

Developmental Aspects GH levels decline with age - accounts for muscle atrophy with age TH declines with age, contributing to lower basal metabolic rates PTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH © 2013 Pearson Education, Inc.