PowerPoint Lecture Slides prepared by Barbara Heard, Human Anatomy & Physiology Atlantic Cape Community College Ninth Edition C H A P T E R 16 The Endocrine System: Part A Endocrine System: Overview Acts with nervous system to coordinate and integrate activity of body cells Influences metabolic activities via hormones transported in blood Response slower but longer lasting than nervous system Endocrinology Study of hormones and endocrine organs Annie Leibovitz/Contact Press Images Endocrine System: Overview Controls and integrates Reproduction Growth and development Maintenance of electrolyte, water, and nutrient balance of blood Regulation of cellular metabolism and energy balance Mobilization of body defenses Endocrine System: Overview Exocrine glands Nonhormonal substances (sweat, saliva) Have ducts to carry secretion to membrane surface Endocrine glands Produce hormones Lack ducts Endocrine System: Overview Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands is neuroendocrine organ Some have exocrine and endocrine functions Pancreas, gonads, placenta Other tissues and organs that produce hormones Adipose cells, thymus, and cells in walls of small intestine, stomach, kidneys, and heart Figure 16.1 Location of selected endocrine organs of the body. Pineal gland Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Gonads Ovary (female) Testis (male) 1
Chemical Messengers Chemistry of Hormones Hormones: long-distance chemical signals; travel in blood or lymph Autocrines: chemicals that exert effects on same cells that secrete them Paracrines: locally acting chemicals that affect cells other than those that secrete them Autocrines and paracrines are local chemical messengers; not considered part of endocrine system Two main classes Amino acid-based hormones Amino acid derivatives, peptides, and proteins Steroids Synthesized from cholesterol Gonadal and adrenocortical hormones Mechanisms of Hormone Action Mechanisms of Hormone Action Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location 1. Water-soluble hormones (all amino acid based hormones except thyroid hormone) Act on plasma membrane receptors Act via G protein second messengers Cannot enter cell 2. Lipid-soluble hormones (steroid and thyroid hormones) Act on intracellular receptors that directly activate genes Can enter cell Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Slide 1 Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Slide 1 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd 1 Hormone (1st messenger) (1st messenger) messenger binds receptor. Adenylate cyclase Extracellular fluid G protein (G s) camp 5 camp activates GTP protein kinases. Receptor GTP ATP GDP Inactive Active GTP protein protein kinase kinase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Extracellular fluid Cytoplasm Nucleus Steroid hormone Receptor protein mrna Plasma membrane 1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor. Receptorhormone complex 2 The receptorhormone complex enters the nucleus. Receptor Binding region DNA 3 The receptor- hormone complex binds a specific DNA region. 4 Binding initiates transcription of the gene to mrna. Cytoplasm 2 Receptor 3 G protein 4 Adenylate activates G activates cyclase converts protein (G s). adenylate ATP to camp (2nd cyclase. messenger). New protein 5 The mrna directs protein synthesis. 2
Target Cell Specificity Target Cell Activation Target cells must have specific receptors to which hormone binds, for example ACTH receptors found only on certain cells of adrenal cortex Thyroxin receptors are found on nearly all cells of body Hormones influence number of their receptors Up-regulation target cells form more receptors in response to low hormone levels Down-regulation target cells lose receptors in response to high hormone levels Figure 16.4a Three types of endocrine gland stimuli. Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Parathyroid glands Capillary (low Ca 2+ in blood) Thyroid gland (posterior view) Slide 1 Neural Stimuli Nerve fibers stimulate hormone release Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines PTH Parathyroid glands Stimulus: Low concentration of Ca 2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca 2+. Figure 16.4b Three types of endocrine gland stimuli. Slide 1 Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Capillary Preganglionic sympathetic fibers Medulla of adrenal gland Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and norepinephrine. Hormonal Stimuli Hormones stimulate other endocrine organs to release their hormones Hypothalamic hormones stimulate release of most anterior pituitary hormones Anterior pituitary hormones stimulate targets to secrete still more hormones Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from final target organs inhibit release of anterior pituitary hormones 3
Figure 16.4c Three types of endocrine gland stimuli. Slide 1 Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Anterior pituitary gland Thyroid gland Adrenal cortex Gonad (Testis) Nervous System Modulation Nervous system modifies stimulation of endocrine glands and their negative feedback mechanisms Example: under severe stress, hypothalamus and sympathetic nervous system activated body glucose levels rise Nervous system can override normal endocrine controls Stimulus: Hormones from hypothalamus. Response: Anterior pituitary gland secretes hormones that stimulate other endocrine glands to secrete hormones. Duration of Hormone Activity Limited Ranges from 10 seconds to several hours Effects may disappear as blood levels drop Some persist at low blood levels Interaction of Hormones at Target Cells Multiple hormones may act on same target at same time Permissiveness: one hormone cannot exert its effects without another hormone being present Synergism: more than one hormone produces same effects on target cell amplification Antagonism: one or more hormones oppose(s) action of another hormone The Pituitary Gland and Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Slide 1 Pituitary gland (hypophysis) has two major lobes Posterior pituitary (lobe) Neural tissue Anterior pituitary (lobe) (adenohypophysis) Glandular tissue Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Axon terminals Hypothalamichypophyseal tract Posterior lobe of pituitary Paraventricular nucleus Supraoptic nucleus Inferior hypophyseal artery Oxytocin ADH 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). 2 Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary. 3 Oxytocin and ADH are stored in axon terminals in the posterior pituitary. 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. 4
Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Anterior lobe of pituitary Superior hypophyseal artery 2 Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary. 3 In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation. GH, TSH, ACTH, FSH, LH, PRL Anterior lobe of pituitary Slide 1 1 When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus. Hypophyseal portal system Primary capillary plexus Hypophyseal portal veins Secondary capillary plexus Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. A portal system is two capillary plexuses (beds) connected by veins. Posterior Pituitary and Hypothalamic Hormones Oxytocin and ADH Each composed of nine amino acids Almost identical differ in two amino acids ADH Anterior Pituitary Hormones Diabetes insipidus ADH deficiency due to hypothalamus or posterior pituitary damage Must keep well-hydrated Syndrome of inappropriate ADH secretion (SIADH) Retention of fluid, headache, disorientation Fluid restriction; blood sodium level monitoring Growth hormone (GH) Thyroid-stimulating hormone (TSH) or thyrotropin Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL) Growth Hormone (GH, or Somatotropin) Produced by somatotropic cells Direct actions on metabolism Increases blood levels of fatty acids; encourages use of fatty acids for fuel; protein synthesis Decreases rate of glucose uptake and metabolism conserving glucose Glycogen breakdown and glucose release to blood (anti-insulin effect) Homeostatic Imbalances of Growth Hormone Hypersecretion In children results in gigantism In adults results in acromegaly Hyposecretion In children results in pituitary dwarfism 5
Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH). Figure 16.7 Disorders of pituitary growth hormone. Feedback Inhibits GHRH release Stimulates GHIH release Anterior pituitary secretes growth hormone releasing hormone (GHRH), and GHIH (somatostatin) Inhibits GH synthesis and release Growth hormone (GH) Indirect actions (growthpromoting) Direct actions (metabolic, anti-insulin) Liver and other tissues Produce Insulin-like growth factors (IGFs) Effects Effects Skeletal Extraskeletal Fat metabolism Carbohydrate metabolism Increases, stimulates Reduces, inhibits Increased cartilage formation and skeletal growth Increased protein synthesis, and cell growth and proliferation Increased fat breakdown and release Increased blood glucose and other anti-insulin effects Initial stimulus Physiological response Result Thyroid-stimulating Hormone (Thyrotropin) Produced by thyrotropic cells of anterior pituitary Stimulates normal development and secretory activity of thyroid Release triggered by thyrotropin-releasing hormone from hypothalamus Inhibited by rising blood levels of thyroid hormones that act on pituitary and hypothalamus Figure 16.8 Regulation of thyroid hormone secretion. TRH Anterior pituitary TSH Thyroid gland Thyroid hormones Target cells Stimulates Inhibits Adrenocorticotropic Hormone (Corticotropin) Regulation of ACTH release Triggered by hypothalamic corticotropinreleasing hormone (CRH) in daily rhythm Internal and external factors such as fever, hypoglycemia, and stressors can alter release of CRH Gonadotropins Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Secreted by gonadotropic cells of anterior pituitary FSH stimulates gamete (egg or sperm) production LH promotes production of gonadal hormones Absent from the blood in prepubertal boys and girls 6
Thyroid Gland Thyroid Hormone (TH) Two lateral lobes connected by median mass called isthmus Composed of follicles that produce glycoprotein thyroglobulin Colloid (fluid with thyroglobulin + iodine) fills lumen of follicles and is precursor of thyroid hormone Parafollicular cells produce the hormone calcitonin Actually two related compounds T 4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atoms T 3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms Affects virtually every cell in body Thyroid Hormone Figure 16.10 Synthesis of thyroid hormone. Thyroid follicular cells Slide 1 Colloid 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 Capillary Iodide (I ) 1 Thyroglobulin is synthesized and discharged into the follicle lumen. Tyrosines (part of thyroglobulin molecule) 4 Iodine is attached to tyrosine in colloid, forming DIT and MIT. Golgi apparatus Rough Thyroglobulin ER Iodine 3 Iodide DIT MIT colloid is oxidized to iodine. 2 Iodide (I ) is trapped (actively transported in). T 4 5 Iodinated tyrosines are T linked together to form T 3 Lysosome 3 and T 4. T 4 6 Thyroglobulin colloid is endocytosed and combined T 3 7 Lysosomal enzymes with a lysosome. T Colloid in 4 cleave T 4 and T 3 from lumen of T thyroglobulin and hormones 3 diffuse into bloodstream. follicle To peripheral tissues Transport and Regulation of TH T 4 and T 3 transported by thyroxine-binding globulins (TBGs) Both bind to target receptors, but T 3 is ten times more active than T 4 Peripheral tissues convert T 4 to T 3 Figure 16.8 Regulation of thyroid hormone secretion. TRH Anterior pituitary TSH Thyroid gland Thyroid hormones Target cells Stimulates Inhibits 7
Homeostatic Imbalances of TH Figure 16.11 Thyroid disorders. Hyposecretion in adults myxedema; goiter if due to lack of iodine Hyposecretion in infants cretinism Hypersecretion most common type is Graves' disease Calcitonin Parathyroid Glands 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 Ca 2+ from bone matrix Stimulates Ca 2+ uptake and incorporation into bone matrix 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 Ca 2+ homeostasis Figure 16.12 The parathyroid glands. Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine. Hypocalcemia (low blood Ca 2+ ) PTH release from parathyroid gland Pharynx (posterior aspect) Capillary Osteoclast activity in bone causes Ca 2+ and PO 3-4 release into blood Ca 2+ reabsorption in kidney tubule Activation of vitamin D by kidney Thyroid gland Esophagus Trachea Parathyroid glands Parathyroid cells (secrete parathyroid hormone) Oxyphil cells Ca 2+ absorption from food in small intestine Ca 2+ in blood Initial stimulus Physiological response Result 8
Homeostatic Imbalances of PTH Adrenal (Suprarenal) Glands Hyperparathyroidism due to tumor Bones soften and deform Elevated Ca 2+ 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 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 Figure 16.14 Microscopic structure of the adrenal gland. Homeostatic Imbalances of Aldosterone Adrenal gland Medulla Cortex Kidney Medulla Cortex Capsule Zona glomerulosa Zona fasciculata Zona reticularis Adrenal medulla Hormones secreted Aldosterone Cortisol and androgens Epinephrine and norepinephrine Aldosteronism hypersecretion due to adrenal tumors Hypertension and edema due to excessive Na + Excretion of K + leading to abnormal function of neurons and muscle Drawing of the histology of the adrenal cortex and a portion of the adrenal medulla Photomicrograph (115x) 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 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 9
Figure 16.16 The effects of excess glucocorticoid. 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 Patient before onset. Same patient with Cushing's syndrome. The white arrow shows the characteristic "buffalo hump" of fat on the upper back. Gonadocorticoids Adrenal Medulla 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 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 Adrenal Medulla Hypersecretion Hyperglycemia, increased metabolic rate, rapid heartbeat and palpitations, hypertension, intense nervousness, sweating Hyposecretion Not problematic Adrenal catecholamines not essential to life Figure 16.17 Stress and the adrenal gland. Short-term stress Nerve impulses Spinal cord Preganglionic sympathetic fibers Adrenal medulla (secretes amino acid based hormones) Catecholamines (epinephrine and norepinephrine) Short-term stress response Heart rate increases Blood pressure increases Bronchioles dilate Liver converts glycogen to glucose and releases glucose to blood Blood flow changes, reducing digestive system activity and urine output Metabolic rate increases Prolonged stress Stress CRH (corticotropinreleasing hormone) Corticotropic cells of anterior pituitary To target in blood Adrenal cortex (secretes steroid hormones) ACTH Mineralocorticoids Glucocorticoids Long-term stress response Kidneys retain Proteins and fats converted sodium and water to glucose or broken down Blood volume and for energy blood pressure Blood glucose increases rise Immune system supressed 10
Pineal Gland Pancreas 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 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) Figure 16.18 Photomicrograph of differentially stained pancreatic tissue. Glucagon Pancreatic islet (Glucagonproducing) cells (Insulinproducing) cells Pancreatic acinar cells (exocrine) 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 Insulin Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels. Stimulates glucose uptake by cells 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 Pancreas Stimulus Blood glucose level Blood glucose rises to normal range. Glucose Insulin Tissue cells Stimulates glycogen formationw Glucose Glycogen Blood Liver glucose falls to normal range. Stimulus Blood glucose level Pancreas Glycogen Liver Stimulates glycogen breakdown Glucagon 11
Factors That Influence Insulin Release Homeostatic Imbalances of Insulin 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 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 O 2 transport; depression of nervous system coma and death possible 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" Homeostatic Imbalances of Insulin Hyperinsulinism: Excessive insulin secretion Causes hypoglycemia Low blood glucose levels Anxiety, nervousness, disorientation, unconsciousness, even death Treated by sugar ingestion Table 16.4 Symptoms of Insulin Deficit (Diabetes Mellitus) 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) 12
Testes Other Hormone-producing Structures 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 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-angiotensinaldosterone mechanism Developmental Aspects 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 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 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 bonedemineralizing effects of PTH 13