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2012-03-15 9 The Endocrine System Yong Jeong, MD, PhD Department of Bio and Brain Engineering The Endocrine System •Second controlling system of the body •Nervous system is the fast-control system •Uses chemical messengers (hormones) that are released into the blood •Hormones control several major processes •Reproduction •Growth and development •Mobilization of body defenses •Maintenance of much of homeostasis •Regulation of metabolism © 2012 Pearson Education, Inc. 1 2012-03-15 Binding of ligands to membrane-spanning receptors activates diverse response mechanisms. © 2012 Pearson Education, Inc. Hormone Overview •Hormones are produced by specialized cells •Cells secrete hormones into extracellular fluids •Blood transfers hormones to target sites •These hormones regulate the activity of other cells © 2012 Pearson Education, Inc. 2 2012-03-15 The Chemistry of Hormones •Hormones are classified chemically as •Amino acid–based, which includes •Proteins •Peptides •Amines •Steroids—made from cholesterol •Prostaglandins—made from highly active lipids © 2012 Pearson Education, Inc. Mechanisms of Hormone Action •Hormones affect only certain tissues or organs (target cells or target organs) •Target cells must have specific protein receptors •Hormone-binding alters cellular activity © 2012 Pearson Education, Inc. 3 2012-03-15 Effects Caused by Hormones •Changes in plasma membrane permeability or electrical state •Synthesis of proteins, such as enzymes •Activation or inactivation of enzymes •Stimulation of mitosis •Promotion of secretory activity © 2012 Pearson Education, Inc. The Chemistry of Hormones •Two mechanisms in which hormones act •Direct gene activation •Second-messenger system © 2012 Pearson Education, Inc. 4 2012-03-15 Direct Gene Activation (Steroid Hormone Action) •Diffuse through the plasma membrane of target cells •Enter the nucleus •Bind to a specific protein within the nucleus •Bind to specific sites on the cell’s DNA •Activate genes that result in synthesis of new proteins © 2012 Pearson Education, Inc. Steroid hormone Nucleus Cytoplasm 1 Receptor protein 2 3 Hormonereceptor complex 4 DNA mRNA 5 New protein Plasma membrane of target cell © 2012 Pearson Education, Inc. 6 Figure 9.1a, step 6 5 2012-03-15 Second-Messenger System (Nonsteroid Hormone Action) •Hormone binds to a membrane receptor •Hormone does not enter the cell •Sets off a series of reactions that activates an enzyme •Catalyzes a reaction that produces a secondmessenger molecule (such as cAMP) •Oversees additional intracellular changes to promote a specific response © 2012 Pearson Education, Inc. Nonsteroid hormone (first messenger) Cytoplasm Enzyme ATP 3 1 2 Receptor protein Plasma membrane of target cell Second cAMP messenger 4 Effect on cellular function, such as glycogen breakdown (b) Nonsteroid hormone action © 2012 Pearson Education, Inc. Figure 9.1b 6 2012-03-15 Control of Hormone Release •Hormone levels in the blood are mostly maintained by negative feedback •A stimulus or low hormone levels in the blood triggers the release of more hormone •Hormone release stops once an appropriate level in the blood is reached © 2012 Pearson Education, Inc. Hormonal Stimuli of Endocrine Glands •Most common stimuli •Endocrine glands are activated by other hormones •Examples: •Anterior pituitary hormones travel to target glands, such as the thyroid gland, to prompt the release of a particular hormone, such as thyroid hormone © 2012 Pearson Education, Inc. 7 2012-03-15 (a) Hormonal stimulus 1 The hypothalamus secretes hormones that… Hypothalamus 2 …stimulate the anterior pituitary gland to secrete hormones that… Thyroid gland Anterior pituitary gland Adrenal Gonad cortex (Testis) 3 …stimulate other endocrine glands to secrete hormones © 2012 Pearson Education, Inc. Figure 9.2a Humoral Stimuli of Endocrine Glands •Changing blood levels of certain ions stimulate hormone release •Humoral indicates various body fluids such as blood and bile •Examples: •Parathyroid hormone and calcitonin are produced in response to changing levels of blood calcium levels •Insulin is produced in response to changing levels of blood glucose levels © 2012 Pearson Education, Inc. 8 2012-03-15 (b) Humoral stimulus 1 Capillary blood contains low concentration of Ca2+, which stimulates… Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid Parathyroid glands PTH glands 2 …secretion of parathyroid hormone (PTH) by parathyroid glands © 2012 Pearson Education, Inc. Figure 9.2b Neural Stimuli of Endocrine Glands •Nerve impulses stimulate hormone release •Most are under the control of the sympathetic nervous system •Examples: •The release of norepinephrine and epinephrine by the adrenal medulla © 2012 Pearson Education, Inc. 9 2012-03-15 (c) Neural stimulus 1 Preganglionic sympathetic fiber stimulates adrenal medulla cells… CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary 2 …to secrete catecholamines (epinephrine and norepinephrine) © 2012 Pearson Education, Inc. Figure 9.2c Major Endocrine Organs •Pituitary gland •Thyroid gland •Parathyroid glands •Adrenal glands •Pineal gland •Thymus gland •Pancreas •Gonads (Ovaries and Testes) •Hypothalamus © 2012 Pearson Education, Inc. 10 2012-03-15 Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) © 2012 Pearson Education, Inc. Figure 9.3 Pituitary Gland •Size of a pea •Hangs by a stalk from the hypothalamus in the brain •Protected by the sphenoid bone •Has two functional lobes •Anterior pituitary—glandular tissue •Posterior pituitary—nervous tissue •Often called the “master endocrine gland” © 2012 Pearson Education, Inc. 11 2012-03-15 Hormones of the Anterior Pituitary •Six anterior pituitary hormones •Two affect non-endocrine targets •Growth hormone •Prolactin •Four stimulate other endocrine glands (tropic hormones) •Thyroid-stimulating hormone (thyrotropic hormone) •Adrenocorticotropic hormone •Two gonadotropic hormones © 2012 Pearson Education, Inc. Hormones of the Anterior Pituitary •Characteristics of all anterior pituitary hormones •Proteins (or peptides) •Act through second-messenger systems •Regulated by hormonal stimuli, mostly negative feedback © 2012 Pearson Education, Inc. 12 2012-03-15 Releasing hormones secreted into portal circulation Hypothalamus Anterior pituitary Posterior pituitary Hypophyseal portal system Adrenocorticotropic hormone (ACTH) Growth hormone (GH) Bones and muscles Prolactin (PRL) Follicle-stimulating Thyrotropic hormone (TH) hormone (FSH) and luteinizing Mammary hormone (LH) glands Thyroid Adrenal cortex Testes or ovaries © 2012 Pearson Education, Inc. Figure 9.4 Hormones of the Anterior Pituitary •Growth hormone •General metabolic hormone •Major effects are directed to growth of skeletal muscles and long bones •Plays a role in determining final body size •Causes amino acids to be built into proteins •Causes fats to be broken down for a source of energy © 2012 Pearson Education, Inc. 13 2012-03-15 Hormones of the Anterior Pituitary •Growth hormone (GH) disorders •Pituitary dwarfism results from hyposecretion of GH during childhood •Gigantism results from hypersecretion of GH during childhood •Acromegaly results from hypersecretion of GH during adulthood © 2012 Pearson Education, Inc. Pituitary dwarf (left), Giant (center), Normal height woman (right) © 2012 Pearson Education, Inc. Figure 9.5 14 2012-03-15 Hormones of the Anterior Pituitary •Prolactin (PRL) •Stimulates and maintains milk production following childbirth •Function in males is unknown •Adrenocorticotropic hormone (ACTH) •Regulates endocrine activity of the adrenal cortex •Thyroid-stimulating hormone (TSH) •Influences growth and activity of the thyroid gland © 2012 Pearson Education, Inc. Hormones of the Anterior Pituitary •Gonadotropic hormones •Regulate hormonal activity of the gonads •Follicle-stimulating hormone (FSH) • Stimulates follicle development in ovaries • Stimulates sperm development in testes •Luteinizing hormone (LH) • Triggers ovulation of an egg in females • Stimulates testosterone production in males © 2012 Pearson Education, Inc. 15 2012-03-15 Pituitary–Hypothalamus Relationship •Hormonal release is regulated by releasing and inhibiting hormones produced by the hypothalamus •Hypothalamus produces two hormones •These hormones are transported to neurosecretory cells of the posterior pituitary •Oxytocin •Antidiuretic hormone •The posterior pituitary is not strictly an endocrine gland, but does release hormones © 2012 Pearson Education, Inc. Hormones of the Posterior Pituitary •Oxytocin •Stimulates contractions of the uterus during labor, sexual relations, and breastfeeding •Causes milk ejection in a nursing woman © 2012 Pearson Education, Inc. 16 2012-03-15 Hormones of the Posterior Pituitary •Antidiuretic hormone (ADH) •Inhibits urine production by promoting water reabsorption by the kidneys •In large amounts, causes vasoconstriction leading to increased blood pressure •Also known as vasopressin © 2012 Pearson Education, Inc. Optic chiasma Axon terminals Hypothalamic neurosecretory cells Hypothalamus Arterial blood supply Posterior lobe Capillary bed Venous drainage Anterior lobe of the pituitary © 2012 Pearson Education, Inc. ADH Oxytocin Kidney tubules Mammary glands Uterine muscles Figure 9.6 17 2012-03-15 Thyroid Gland •Found at the base of the throat •Consists of two lobes and a connecting isthmus •Produces two hormones •Thyroid hormone •Calcitonin © 2012 Pearson Education, Inc. Thyroid cartilage Epiglottis Common carotid artery Isthmus of thyroid gland Trachea Brachiocephalic artery Left subclavian artery Left lobe of thyroid gland Aorta (a) Gross anatomy of the thyroid gland, anterior view © 2012 Pearson Education, Inc. Figure 9.7a 18 2012-03-15 Thyroid Gland •Thyroid hormone •Major metabolic hormone •Composed of two active iodine-containing hormones •Thyroxine (T4)—secreted by thyroid follicles •Triiodothyronine (T3)—conversion of T4 at target tissues © 2012 Pearson Education, Inc. Colloid-filled Follicle cells follicles Parafollicular cell © 2012 Pearson Education, Inc. (b) Photomicrograph of thyroid gland follicles (125×) Figure 9.7b 19 2012-03-15 Thyroid Gland •Thyroid hormone disorders •Goiters •Thyroid gland enlarges due to lack of iodine •Salt is iodized to prevent goiters •Cretinism •Caused by hyposecretion of thyroxine •Results in dwarfism during childhood © 2012 Pearson Education, Inc. © 2012 Pearson Education, Inc. Figure 9.8 20 2012-03-15 Thyroid Gland •Thyroid hormone disorders (continued) •Myxedema •Caused by hypothyroidism in adults •Results in physical and mental slugishness •Graves’ disease •Caused by hyperthyroidism •Results in increased metabolism, heat intolerance, rapid heartbeat, weight loss, and exophthalmos © 2012 Pearson Education, Inc. © 2012 Pearson Education, Inc. Figure 9.9 21 2012-03-15 Thyroid Gland •Calcitonin •Decreases blood calcium levels by causing its deposition on bone •Antagonistic to parathyroid hormone •Produced by parafollicular cells •Parafollicular cells are found between the follicles © 2012 Pearson Education, Inc. Colloid-filled Follicle cells follicles Parafollicular cell © 2012 Pearson Education, Inc. (b) Photomicrograph of thyroid gland follicles (125×) Figure 9.7b 22 2012-03-15 Parathyroid Glands •Tiny masses on the posterior of the thyroid •Secrete parathyroid hormone (PTH) •Stimulate osteoclasts to remove calcium from bone •Stimulate the kidneys and intestine to absorb more calcium •Raise calcium levels in the blood © 2012 Pearson Education, Inc. Calcitonin Calcitonin stimulates calcium salt deposit in bone. Thyroid gland releases calcitonin. Stimulus Rising blood Ca2+ levels BALANCE Calcium homeostasis of blood: 9–11 mg/100 ml BALANCE Stimulus Falling blood Ca2+ levels Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood. © 2012 Pearson Education, Inc. Parathyroid glands PTH Parathyroid glands release parathyroid hormone (PTH). Figure 9.10 23 2012-03-15 Adrenal Glands •Sit on top of the kidneys •Two regions •Adrenal cortex—outer glandular region has three layers •Mineralocorticoids secreted by outermost layer •Glucocorticoids secreted by middle layer •Sex hormones secreted by innermost layer •Adrenal medulla—inner neural tissue region © 2012 Pearson Education, Inc. Adrenal gland Capsule Mineralocorticoidsecreting area Adrenal gland • Medulla • Cortex Cortex Kidney Adrenal cortex Sex hormone secreting area Medulla Kidney © 2012 Pearson Education, Inc. Glucocorticoidsecreting area Adrenal medulla Figure 9.11 24 2012-03-15 Hormones of the Adrenal Cortex •Mineralocorticoids (mainly aldosterone) •Produced in outer adrenal cortex •Regulate mineral content in blood •Regulate water and electrolyte balance •Target organ is the kidney •Production stimulated by renin and aldosterone •Production inhibited by atrial natriuretic peptide (ANP) © 2012 Pearson Education, Inc. Decreased Na+ or increased K+ in blood Stress Hypothalamus Decreased blood volume and/or blood pressure Corticotropinreleasing hormone Anterior pituitary Increased ACTH blood pressure or blood volume Kidney Renin Indirect stimulating effect via angiotensin Angiotensin II Direct stimulating effect Heart Atrial natriuretic peptide (ANP) Inhibitory effect Mineralocorticoidproducing part of adrenal cortex Enhanced secretion of aldosterone targets kidney tubules © 2012 Pearson Education, Inc. Increased absorption of Na+ and water; increased K+ excretion Increased blood volume and blood pressure Figure 9.12 25 2012-03-15 Hormones of the Adrenal Cortex •Glucocorticoids (including cortisone and cortisol) •Produced in the middle layer of the adrenal cortex •Promote normal cell metabolism •Help resist long-term stressors •Released in response to increased blood levels of ACTH © 2012 Pearson Education, Inc. Short term Stress More prolonged Hypothalamus Releasing hormones Spinal cord Nerve impulses Corticotropic cells of anterior pituitary Preganglionic Adrenal sympathetic medulla fibers ACTH Adrenal cortex Mineralocorticoids Glucocorticoids Short-term stress response Catecholamines 1. Increased heart rate 2. Increased blood pressure (epinephrine and 3. Liver converts glycogen norepinephrine) to glucose and releases glucose to blood 4. Dilation of bronchioles 5. Changes in blood flow patterns, leading to increased alertness and decreased digestive and kidney activity 6. Increased metabolic rate © 2012 Pearson Education, Inc. Long-term stress response 1. Retention of sodium 1. Proteins and fats converted to and water by kidneys glucose or broken 2. Increased blood down for energy volume and blood 2. Increased blood pressure sugar 3. Suppression of immune system Figure 9.13 26 2012-03-15 Hormones of the Adrenal Cortex •Sex hormones •Produced in the inner layer of the adrenal cortex •Small amounts are made throughout life •Mostly androgens (male sex hormones) are made but some estrogens (female sex hormones) are also formed © 2012 Pearson Education, Inc. Adrenal Glands • Adrenal cortex disorders • Addison’s disease • Results from hyposecretion of all adrenal cortex hormones • Bronze skin tone, muscles are weak, burnout, susceptibility to infection • Hyperaldosteronism • May result from an ACTH-releasing tumor • Excess water and sodium are retained leading to high blood pressure and edema © 2012 Pearson Education, Inc. 27 2012-03-15 Adrenal Glands • Adrenal cortex disorders • Cushing’s syndrome • Results from a tumor in the middle cortical area of the adrenal cortex • “Moon face,” “buffalo hump” on the upper back, high blood pressure, hyperglycemia, weakening of bones, depression • Masculinization • Results from hypersecretion of sex hormones • Beard and male distribution of hair growth © 2012 Pearson Education, Inc. Hormones of the Adrenal Medulla •Produces two similar hormones (catecholamines) •Epinephrine (adrenaline) •Norepinephrine (noradrenaline) •These hormones prepare the body to deal with short-term stress (“fight or flight”) by •Increasing heart rate, blood pressure, blood glucose levels •Dilating small passageways of lungs © 2012 Pearson Education, Inc. 28 2012-03-15 Adrenal gland Capsule Mineralocorticoidsecreting area Adrenal gland • Medulla • Cortex Cortex Kidney Glucocorticoidsecreting area Adrenal cortex Sex hormone secreting area Medulla Kidney © 2012 Pearson Education, Inc. Adrenal medulla Figure 9.11 Pancreatic Islets •The pancreas is a mixed gland and has both endocrine and exocrine functions •The pancreatic islets produce hormones •Insulin—allows glucose to cross plasma membranes into cells from beta cells •Glucagon—allows glucose to enter the blood from alpha cells •These hormones are antagonists that maintain blood sugar homeostasis © 2012 Pearson Education, Inc. 29 2012-03-15 Stomach Pancreas (a) Figure 9.14a © 2012 Pearson Education, Inc. Exocrine cells of pancreas (b) © 2012 Pearson Education, Inc. Pancreatic islets Figure 9.14b 30 2012-03-15 Exocrine cells of pancreas Alpha (α) cells Capillaries Cord of beta (β) cells secreting insulin into capillaries (c) Figure 9.14c © 2012 Pearson Education, Inc. Uptake of glucose from blood is enhanced in most body cells Insulin-secreting cells of the pancreas activated; release insulin into the blood Insulin Pancreas Elevated blood sugar level Tissue cells Glucose Glycogen Liver takes up glucose and stores as glycogen Stimulus Blood glucose level (e.g., after eating four jelly doughnuts) Stimulus Blood glucose level (e.g., after skipping a meal) Blood glucose rises to homeostatic set point; stimulus for glucagon release diminishes Glucose Glycogen Liver breaks down glycogen stores and Liver releases glucose to the blood © 2012 Pearson Education, Inc. Blood glucose falls to homeostatic set point; stimulus for insulin release diminishes Low blood sugar level Glucagon-releasing cells of pancreas activated; release glucagon into blood Glucagon Figure 9.15 31 2012-03-15 Pineal Gland •Found on the third ventricle of the brain •Secretes melatonin •Helps establish the body’s wake and sleep cycles •Believed to coordinate the hormones of fertility in humans © 2012 Pearson Education, Inc. Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) © 2012 Pearson Education, Inc. Figure 9.3 32 2012-03-15 Thymus Gland •Located posterior to the sternum •Largest in infants and children •Produces thymosin •Matures some types of white blood cells •Important in developing the immune system © 2012 Pearson Education, Inc. Gonads •Ovaries •Produce eggs •Produce two groups of steroid hormone •Estrogens •Progesterone •Testes •Produce sperm •Produce androgens, such as testosterone © 2012 Pearson Education, Inc. 33 2012-03-15 Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus Adrenal glands Pancreas Ovary (female) Testis (male) © 2012 Pearson Education, Inc. Figure 9.3 Hormones of the Ovaries •Estrogens •Stimulate the development of secondary female characteristics •Mature female reproductive organs •With progesterone, estrogens also •Promote breast development •Regulate menstrual cycle © 2012 Pearson Education, Inc. 34 2012-03-15 Hormones of the Ovaries •Progesterone •Acts with estrogen to bring about the menstrual cycle •Helps in the implantation of an embryo in the uterus •Helps prepare breasts for lactation © 2012 Pearson Education, Inc. Menstrual cycle © 2012 Pearson Education, Inc. 35 2012-03-15 Hormones of the Testes •Produce several androgens •Testosterone is the most important androgen •Responsible for adult male secondary sex characteristics •Promotes growth and maturation of male reproductive system •Required for sperm cell production © 2012 Pearson Education, Inc. Other Hormone-Producing Tissues and Organs •Parts of the small intestine •Parts of the stomach •Kidneys •Heart •Many other areas have scattered endocrine cells © 2012 Pearson Education, Inc. 36 2012-03-15 Endocrine Function of the Placenta •Produces hormones that maintain the pregnancy •Some hormones play a part in the delivery of the baby •Produces human chorionic gonadotropin (hCG) in addition to estrogen, progesterone, and other hormones © 2012 Pearson Education, Inc. Developmental Aspects of the Endocrine System •Most endocrine organs operate smoothly until old age •Menopause is brought about by lack of efficiency of the ovaries •Problems associated with reduced estrogen are common •Growth hormone production declines with age •Many endocrine glands decrease output with age © 2012 Pearson Education, Inc. 37