13 The Endocrine System 1

The Endocrine System Produces Hormones Endocrine system: collection of specialized cells, and tissues that secrete hormones Endocrine glands: ductless organs that secrete hormones into blood, interstitial fluid, lymph Hormones Chemical messengers secreted by endocrine glands Circulate in the bloodstream Act on specific cells in the body (target cells) that have the appropriate hormone receptor

Hypothalamus Pituitary gland Hypothalamus Pineal gland Pituitary gland Figure 13.1 Hypothalamus Pituitary gland • Anterior lobe • Posterior lobe Hypothalamus • Releasing hormones • Inhibiting hormones Pineal gland Pituitary gland • Melatonin Anterior lobe Thyroid gland • Adrenocorticotropic hormone (ACTH) • Thyroid-stimulating hormone (TSH) • Thyroxine • Follicle-stimulating hormone (FSH) • Triiodothyronine • Luteinizing hormone (LH) • Calcitonin • Prolactin Parathyroid glands • Growth hormone • Parathyroid hormone (PTH) Posterior lobe • Antidiuretic hormone (ADH) Thymus gland • Oxytocin • Thymosin • Thymopoietin Adrenal glands Heart Cortex • Atrial natriuretic hormone • Cortisol Stomach Figure 13.1 Components of the human endocrine system. • Aldosterone Medulla • Gastrin • Epinephrine Pancreas • Norepinephrine • Glucagon • Insulin Kidneys • Somatostatin • Erythropoietin Intestines • Renin • Secretin Ovaries (Female) • Cholecystokinin • Estrogen Testes (Male) • Progesterone • Testosterone 3

The Endocrine System Produces Hormones Hormones have access to every cell Each hormone acts only on specific cells (target cells) Only specific cells have receptors for specific hormones Endocrine control is slower than nervous system Endocrine and nervous systems interact

Hormones Are Classified as Steroid and Nonsteroid Steroid hormones Structurally related to cholesterol Lipid soluble Nonsteroid hormones Structurally related to proteins Lipid insoluble

Steroid Hormones Enter Target Cells Lipid soluble, chemically derived from cholesterol Enter target cells Bind to intracellular receptor Activate specific genes to produce specific proteins Slower acting than nonsteroid hormones; minutes to hours

Capillary Interstitial fluid 1 Nucleus 2 3 4 Cell cytoplasm Figure 13.2 Capillary Steroid hormone Interstitial fluid 1 Hormone diffuses Target cell membrane Hormone receptor Hormone- receptor complex Nucleus 2 DNA Gene activated RNA Figure 13.2 Mechanism of steroid hormone action on a target cell. 3 Protein synthesis New protein 4 New protein alters cell activity Cell cytoplasm 7

Nonsteroid Hormones Bind to Receptors on Target Cell Membranes Water soluble Bind to receptors on target cell membranes Work through intermediate mechanisms to activate existing enzymes May involve a “second messenger” within the cell, such as cyclic AMP (cAMP) Faster action than steroid hormones; seconds to minutes

Cyclic AMP (second messenger) Figure 13.3 Capillary Nonsteroid hormone (first messenger) 1 Interstitial fluid Hormone binds to receptor; cyclic AMP generated within the cell Receptor Enzyme Target cell membrane Cyclic AMP (second messenger) ATP 2 Enzyme 1 activated Cell cytoplasm 3 Figure 13.3 Mechanism of nonsteroid hormone action on a target cell. Enzyme 2 activated 4 Enzyme 3 activated 5 Nucleus Final product alters cell activity 9

Hormones Participate in Negative Feedback Loops Many hormones participate in internal homeostatic control mechanisms Negative feedback loop involving hormones includes the following: Endocrine gland serves as the control center Hormone is the pathway between the control center and the effectors Target tissues or organs are the effectors

Controlled variable Hormone Higher Set point Lower Figure 13.4 Controlled variable Higher Set point Lower (Reversal of initial change) Endocrine gland (control center) Figure 13.4 A negative feedback loop involving a hormone. Hormone Target cells, tissues, and organs (effectors) 11

The Hypothalamus and the Pituitary Gland Homeostatic control center of the brain Links nervous system and endocrine system Produces two hormones of its own Monitors and controls hormone secretions of the pituitary gland Pituitary gland “Master” gland Secretes eight different hormones that regulate other endocrine organs Two lobes: posterior and anterior

Posterior Pituitary Stores ADH and Oxytocin Posterior pituitary is connected to hypothalamus by neuroendocrine cells Hormones (ADH and oxytocin) made in cell bodies in hypothalamus are transported down axons to axon endings in posterior pituitary for storage and release Posterior pituitary hormones: nonsteroidal Antidiuretic hormone (ADH) Conserves water in kidneys Regulates water balance in body Oxytocin Causes uterine contractions during labor and milk ejection through neuroendocrine reflex

Neuroendocrine cells Hypothalamus Anterior pituitary Figure 13.5 Neuroendocrine cells Hypothalamus Anterior pituitary Posterior pituitary Oxytocin ADH Figure 13.5 Posterior pituitary lobe and hypothalamus. 14

Neuroendocrine cells release oxytocin when stimulated. Figure 13.6 Neuroendocrine cell 3 Neuroendocrine cells release oxytocin when stimulated. Hypothalamus Anterior pituitary 4 Spinal cord Oxytocin is transported by blood to mammary glands. 2 Sensory and spinal nerves carry impulses to the neuroendocrine cells of hypothalamus. Posterior pituitary Milk ejected Figure 13.6 The control of oxytocin secretion by nursing. Oxytocin 1 Nursing stimulates nerve receptors in nipple. 15

The Anterior Pituitary Produces Six Key Hormones Controlled by hypothalamus Releasing and inhibiting hormones from hypothalamus travel to pituitary through pituitary portal system The release of each anterior pituitary hormone is controlled, at least partially, by the hypothalamus

The Anterior Pituitary Produces Six Key Hormones ACTH (adrenocorticotropic hormone) Stimulates adrenal cortex to release glucocorticoids (cortisol) TSH (thyroid-stimulating hormone) Acts on thyroid gland, promoting release of thyroid hormones FSH and LH (gonadotropins) Stimulate growth, development, and function of ovaries and testes Not produced until about age 10–13 (puberty) Increase in production initiates sexual maturation and development at puberty

The Anterior Pituitary Produces Six Key Hormones Prolactin Stimulates development of mammary glands and milk production Growth hormone Has widespread effects on body Major effects on bone, muscle Most of its growth-promoting effects occur during childhood and adolescence

Anterior pituitary hormones Figure 13.7 Neuroendocrine cells Hypothalamus 1 Neuroendocrine cells in hypothalamus produce and secrete releasing and inhibiting hormones 2 Blood flow The pituitary portal blood system carries releasing and inhibiting hormones directly to the anterior pituitary Anterior pituitary endocrine cells 3 The anterior pituitary produces six hormones that enter the general circulation Posterior pituitary Anterior pituitary hormones Figure 13.7 The relationship between the hypothalamus and the anterior pituitary gland. Adreno- corticotropic hormone (ACTH) Thyroid- stimulating hormone (TSH) Follicle- stimulating hormone (FSH) Luteinizing hormone (LH) Growth hormone (GH) Prolactin (PRL) Adrenal cortex Thyroid gland Ovaries or testes Ovaries or testes Mammary glands Skeletal muscle, bone 19

Pituitary Disorders: Hypersecretion and Hyposecretion Diabetes insipidus Hyposecretion of ADH results in inability to conserve water appropriately Causes excessive urination, dehydration, thirst Gigantism Hypersecretion of growth hormone in childhood Acromegaly Excessive growth hormone over a long period in adults Pituitary dwarfism Hyposecretion of growth hormone Treated by administration of GH throughout childhood

Figure 13.8 Figure 13.8 Effect of growth hormone on body growth. 21

Figure 13.9 Figure 13.9 Effect of excessive growth hormone as an adult. 22

The Pancreas Secretes Glucagon, Insulin, and Somatostatin The pancreas has both exocrine and endocrine functions Pancreatic hormones are involved in regulating blood glucose levels Endocrine cells in islets of Langerhans within the pancreas secrete the following three hormones: Alpha cells: secrete glucagon Beta cells: secrete insulin Delta cells: secrete somatostatin

The Pancreas Secretes Glucagon, Insulin, and Somatostatin Raises blood sugar Causes breakdown of glycogen to glucose in liver Insulin Lowers blood sugar Promotes uptake of sugar by cells in liver, muscle, and adipose tissue Promotes conversion of glucose into glycogen, proteins, fat, Somatostatin Inhibits secretion of glucagon and insulin, regulates other hormones

Blood glucose concentration (mg/100 mL) Figure 13.10 Glucagon secretion is inhibited Pancreas secretes insulin 200 The liver uses glucose to produce glycogen Muscle cells use glucose to make glycogen and proteins Adipose tissues use glucose to produce fats for storage High blood glucose 160 120 Blood glucose concentration (mg/100 mL) 80 Meal The liver converts stored glycogen to glucose Figure 13.10 How the pancreas responds to a meal. Low blood glucose 40 Insulin secretion is inhibited Pancreas secretes glucagon 1 1 2 3 4 5 6 Time (hours) 25

The Adrenal Glands Comprise the Cortex and Medulla Adrenal cortex: outer layer of adrenal gland Glucocorticoids, such as cortisol Mineralocorticoids, such as aldosterone Adrenal medulla: inner layer of adrenal gland Epinephrine (adrenaline) Norepinephrine (noradrenaline)

The Adrenal Cortex: Glucocorticoids and Mineralocorticoids Glucocorticoids (Cortisol is an example) Secretion mediated through hypothalamus-pituitary secretions Maintain blood glucose levels during prolonged fasting Suppress inflammatory responses Mineralocorticoids (Aldosterone is an example) Regulate sodium, potassium, water balance Act on kidneys, promoting sodium reabsorption and potassium excretion

The Adrenal Medulla: Epinephrine and Norepinephrine Neuroendocrine organ Secretion stimulated by Sympathetic nervous system Hormones: nonsteroidal Epinephrine and norepinephrine Enhance function of sympathetic nervous system (fight-or-flight response)

Norepinephrine and epinephrine Figure 13.11 Perceived or real threat Brain Activation of sympathetic nerves Adrenal medulla Figure 13.11 Secretion of norepinephrine and epinephrine by the adrenal medulla. Adrenal cortex Norepinephrine and epinephrine Target cells 29

Thyroid and Parathyroid Glands Thyroid located just below larynx in neck Parathyroid glands embedded in back of thyroid Both thyroid and parathyroid are involved in calcium balance Thyroid is also involved in regulating metabolism

Anterior (front) Posterior (back) Figure 13.12 Opening to trachea Larynx Thyroid gland Parathyroids Trachea Figure 13.12 The thyroid and parathyroid glands. Anterior (front) Posterior (back) 31

The Thyroid Gland: Thyroxine Speeds Cellular Metabolism Secretion: mediated through hypothalamus-pituitary secretions Steroidal hormones Thyroxine (T4) and Triiodothyronine (T3) Both regulate production of ATP from glucose and modify the metabolic rate Calcitonin Lowers blood calcium levels Decreases rate of bone resorption by inhibiting osteoclasts Stimulates uptake of calcium by bones

Plasma thyroxine concentration Figure 13.13 Plasma thyroxine concentration Increase Set point Decrease Thyroxine Thyroid gland Hypothalamus Cold temperatures Figure 13.13 Negative feedback control of thyroxine secretion. TSH Releasing hormone Anterior pituitary 33

Iodine Deficiency Can Cause Goiter Iodine is required for the production of active thyroid hormones Inadequate dietary iodine leads to underproduction of thyroid hormones The feedback response to inadequate thyroid hormone is for the hypothalamus and pituitary to further stimulate the thyroid gland in a vicious cycle that causes hypertrophy of the thyroid (goiter)

Figure 13.14 Figure 13.14 A goiter caused by dietary iodine deficiency. 35

Calcitonin Promotes Bone Growth Calcitonin inhibits osteoclasts This decreases bone resorption Calcitonin also stimulates the uptake of calcium by bones Particularly important for bone growth and development in children Combined effects: lower blood calcium levels

Parathyroid Hormone (PTH) Controls Blood Calcium Levels Secretion Response to lowered blood calcium levels Action Removes calcium and phosphate from bone Increases absorption of calcium by the digestive tract Causes kidneys to retain calcium and excrete phosphate Combined effects increase blood calcium levels Major regulator of blood calcium concentration in adults

Figure 13.15 Blood Ca2+ concentration Increase Return of blood Ca2+ toward normal Set point Decrease Vitamin D Bones release Ca2+ Digestive tract absorbs Ca2+ Kidneys save Ca2+ Parathyroid gland Thyroid gland PTH Calcitonin Responses to a fall in blood calcium. Blood Ca2+ concentration Increase Return of blood Ca2+ toward normal Set point Decrease Figure 13.15 The homeostatic regulation of blood calcium concentration. Vitamin D Bones take up Ca2+ Digestive tract absorbs less Ca2+ Kidneys secrete more Ca2+ Parathyroid gland Thyroid gland PTH Calcitonin Responses to a rise in blood calcium. The importance of calcitonin is greatest in children, declining once adulthood is reached. 38

Testes Produce Testosterone Functions of testosterone and other androgens (other testosterone-like steroid hormones) Before birth, responsible for development of external male genitalia At onset of puberty Regulates development and normal functioning of sperm, male reproductive organs, and male sex drive Regulates development of male secondary sex characteristics Small amounts of androgens produced by adrenal glands in both sexes

Ovaries Produce Estrogen and Progesterone Hormones: steroidal Estrogen Initiates development of secondary sex characteristics Regulates menstrual cycle Progesterone

Table 13.2 Table 13.2 Hormones of endocrine glands other than the hypothalamus and pituitary. 41

Other Glands and Organs Also Secrete Hormones Thymus Located in the upper chest, over the heart Secretes thymosin and thymopoietin Assist maturation of T lymphocytes Most active during early development and childhood Pineal gland Located deep within the brain but receives input from optic nerve Secretes melatonin May be important in synchronizing the body’s circadian cycle

Endocrine Functions of the Heart, the Digestive System, and the Kidneys Atrial natriuretic hormone (ANH) Helps regulate blood pressure by increasing rate of sodium and water excretion in the urine Digestive system Gastrin, secretin, cholecystokinin Effects on stomach, pancreas, gall bladder Kidney Erythropoietin Stimulates production of erythrocytes Renin Stimulates aldosterone secretion and constricts blood vessels

Table 13.3 Table 13.3 Hormones of the digestive tract, kidneys, and heart. 44

Other Chemical Messengers Histamine Secreted by mast cells in response to injury or allergy Initiates and enhances inflammation Prostaglandins Local control of blood flow Contribute to inflammatory response Nitric oxide Regulates local blood flow in many tissues Controls penile erection Regulates smooth muscle contraction in digestive tract Antibacterial chemical made by macrophages Neurotransmitter in the brain Growth factors Local acting, modulate development of specific tissues

Disorders of the Endocrine System Diabetes mellitus Disorder of blood sugar regulation Inability to get glucose into cells where it can be used, results in high blood sugar levels Glucose and excess water appear in the urine Abnormal metabolism of carbohydrates, proteins, and lipids causes most of the complications Symptoms: dehydration, thirst, fatigue, frequent infections, blurred vision, tingling of hands/feet Two types: type 1 and type 2

Disorders of the Endocrine System Type 1 diabetes Pancreas does not produce enough insulin Also known as insulin dependent diabetes Treated with insulin injections Results from autoimmune destruction of beta cells of pancreatic islets May be a genetic component and/or environmental trigger Typical onset is during childhood or adolescence 5–10% of all cases of diabetes

Disorders of the Endocrine System Type 2 diabetes Non-insulin dependent Characterized by insulin resistance: cells fail to respond appropriately to insulin Most often seen in adults over 40 Lifestyle factors (diet, exercise) play a role in onset Treatment: lifestyle changes, variety of medications 90–95% of all cases of diabetes

Disorders of the Endocrine System Hypothyroidism: underactive thyroid gland Children: cretinism slowed body growth, altered brain development, delayed puberty Adults: myxedema edema, lethargy, weight gain, low BMR Hyperthyroidism: overactive thyroid gland Increased BMR, hyperactivity, nervousness, agitation, weight loss Graves’ disease: autoimmune form of hyperthyroidism

Disorders of the Endocrine System Adrenal gland disorders Addison’s disease Failure of adrenal cortex Hyposecretion of cortisol and aldosterone Lowers blood glucose and sodium Slow to develop, chronic fatigue, weakness, abdominal pain, weight loss, bronzing of the skin Cushing’s syndrome Excessive cortisol secretion Excessive production of glucose from glycogen Retention of too much salt and water Loss of muscle mass, change in fat distribution Similar symptoms seen with use of cortisol and cortisol-like drugs

Figure 13.16 Figure 13.16 Cushing’s syndrome. Before the disease. During the disease a characteristic hump of fat develops at the back of the neck. 51