Endocrine System PDF

BM New Vision Invited Lecturer- Ivditi Okuashvili 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...

BM New Vision Invited Lecturer- Ivditi Okuashvili 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 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 Hypothalamus 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 Hypothalamus Pituitary gland Thyroid gland Parathyroid glands (on dorsal aspect of thyroid gland) Thymus Adrenal glands Pancreas Gonads Ovary (female) Testis (male) Chemical Messengers 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 Chemistry of Hormones 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 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 Mechanisms of Hormone Action 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 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 Inactive Active GDP GTP protein protein kinase kinase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 Receptor 3 G protein 4 Adenylate activates G activates cyclase converts protein (G s). adenylate ATP to cAMP (2nd cyclase. messenger). Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Slide 1 Steroid Extracellular hormone Plasma fluid membrane 1 The steroid hormone diffuses through the plasma membrane and binds an Cytoplasm intracellular receptor. Receptor Receptor- protein hormone complex 2 The receptor- hormone complex enters the nucleus. Receptor Nucleus Binding region 3 The receptor- hormone complex binds a specific DNA region. DNA 4 Binding initiates transcription of the gene to mRNA. mRNA 5 The mRNA directs protein synthesis. New protein Target Cell Specificity 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 Target Cell Activation 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. Slide 1 Humoral Stimulus Hormone release caused by altered levels of certain critical ions or nutrients. Capillary (low Ca2+ in blood) Thyroid gland (posterior view) Parathyroid glands Parathyroid glands PTH Stimulus: Low concentration of Ca2+ in capillary blood. Response: Parathyroid glands secrete parathyroid hormone (PTH), which increases blood Ca2+. Neural Stimuli Nerve fibers stimulate hormone release Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines  Figure 16.4b Three types of endocrine gland stimuli. Slide 1 Neural Stimulus Hormone release caused by neural input. CNS (spinal cord) Preganglionic sympathetic fibers Medulla of adrenal gland Capillary Stimulus: Action potentials in preganglionic sympathetic fibers to adrenal medulla. Response: Adrenal medulla cells secrete epinephrine and norepinephrine. © 2013 Pearson Education, Inc. 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 Figure 16.4c Three types of endocrine gland stimuli. Slide 1 Hormonal Stimulus Hormone release caused by another hormone (a tropic hormone). Hypothalamus Anterior pituitary gland Thyroid Adrenal Gonad gland cortex (Testis) 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 Hypothalamus Pituitary gland (hypophysis) has two major lobes Posterior pituitary (lobe) Neural tissue Anterior pituitary (lobe) (adenohypophysis) Glandular tissue  Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2). Slide 1 Paraventricular nucleus Hypothalamus 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). Posterior lobe of pituitary Optic chiasma Supraoptic nucleus Infundibulum 2 Oxytocin and ADH are (connecting stalk) transported down the axons of Inferior the hypothalamic- hypophyseal Hypothalamic- hypophyseal tract to the posterior pituitary. hypophyseal artery tract Axon terminals 3 Oxytocin and ADH are stored in axon terminals in Posterior lobe the posterior pituitary. of pituitary Oxytocin 4 When hypothalamic neurons ADH fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.  Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2). Slide 1 Hypothalamus Hypothalamic neurons synthesize GHRH, GHIH, TRH, Anterior lobe CRH, GnRH, PIH. of pituitary Superior hypophyseal artery 1 When appropriately stimulated, 2 Hypothalamic hormones hypothalamic neurons secrete travel through portal veins to releasing or inhibiting hormones the anterior pituitary where into the primary capillary plexus. they stimulate or inhibit Hypophyseal release of hormones made in the anterior pituitary. portal system Primary capillary 3 In response to releasing plexus A portal hormones, the anterior Hypophyseal system is pituitary secretes hormones portal veins two into the secondary capillary capillary plexus. This in turn empties Secondary plexuses into the general circulation. capillary plexus (beds) connected GH, TSH, ACTH, by veins. FSH, LH, PRL Anterior lobe of pituitary  Posterior Pituitary and Hypothalamic Hormones Oxytocin and ADH Each composed of nine amino acids Almost identical – differ in two amino acids Anterior Pituitary Hormones Growth hormone (GH) Thyroid-stimulating hormone (TSH) or thyrotropin Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL) Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH). Hypothalamus secretes growth Feedback Inhibits GHRH release hormone–releasing Stimulates GHIH release hormone (GHRH), and Anterior pituitary GHIH (somatostatin) Inhibits GH synthesis and release Growth hormone (GH) Indirect actions Direct actions (growth- (metabolic, promoting) anti-insulin) Liver and other tissues Produce Insulin-like growth factors (IGFs) Effects Effects Fat Carbohydrate Skeletal Extraskeletal metabolism metabolism Increases, stimulates Reduces, inhibits Increased protein Initial stimulus Increased cartilage Increased Increased blood synthesis, and formation and fat breakdown glucose and other Physiological response cell growth and skeletal growth and release anti-insulin effects proliferation Result Figure 16.7 Disorders of pituitary growth hormone. Figure 16.8 Regulation of thyroid hormone secretion. Hypothalamus TRH Anterior pituitary TSH Thyroid gland Thyroid hormones Stimulates Target cells Inhibits Thyroid Gland 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 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 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. Figure 16.10 Synthesis of thyroid hormone. Slide 1 Thyroid follicular cells Colloid 1 Thyroglobulin is synthesized and discharged into the follicle lumen. Tyrosines (part of thyroglobulin molecule) Capillary 4 Iodine is attached to tyrosine in colloid, forming DIT and MIT. Golgi apparatus Rough Thyro- ER Iodine globulin 3 Iodide DIT MIT colloid is oxidized to iodine. Iodide (I−) 2 Iodide (I –) is trapped (actively transported in). T4 5 Iodinated tyrosines are T3 linked together to form T3 Lysosome and T 4. T4 6 Thyroglobulin colloid is endocytosed and combined T3 7 Lysosomal enzymes with a lysosome. T4 Colloid in cleave T4 and T 3 from lumen of T3 thyroglobulin and hormones diffuse into bloodstream. follicle To peripheral tissues Homeostatic Imbalances of TH Hyposecretion in adults—myxedema; Hyposecretion in goiter if due to lack infants—cretinism of iodine Hypersecretion— most common type is Graves' disease Figure 16.11 Thyroid disorders. 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 Ca 2+ from bone matrix Stimulates Ca2+ uptake and incorporation into bone matrix 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 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 Ca2+ reabsorption Activation of in bone causes Ca 2+ in kidney tubule vitamin D by kidney and PO 43- release into blood Ca2+ absorption from food in small intestine Ca2+ in blood Initial stimulus Physiological response Result 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 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  Figure 16.14 Microscopic structure of the adrenal gland. Hormones Capsule secreted Zona glomerulosa Aldosterone Zona fasciculata Cortex Adrenal gland Medulla Cortex Cortisol and androgens Kidney Zona reticularis Medulla Adrenal medulla Epinephrine and norepinephrine Drawing of the histology of the Photomicrograph (115x) adrenal cortex and a portion of the adrenal medulla 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 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 Figure 16.16 The effects of excess glucocorticoid. Patient before Same patient with Cushing's onset. syndrome. The white arrow shows the characteristic "buffalo hump" of fat on the upper back. 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 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 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 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 Prolonged stress Stress Nerve impulses Hypothalamus CRH (corticotropin- releasing hormone) Spinal cord Corticotropic cells of anterior pituitary Preganglionic To target in blood sympathetic fibers Adrenal cortex Adrenal medulla (secretes steroid (secretes amino acid– hormones) based hormones) ACTH Catecholamines Mineralocorticoids Glucocorticoids (epinephrine and norepinephrine) Short-term stress response Long-term stress response Heart rate increases Kidneys retain Proteins and fats converted Blood pressure increases sodium and water to glucose or broken down Bronchioles dilate Blood volume and for energy Liver converts glycogen to glucose and releases blood pressure Blood glucose increases glucose to blood rise Immune system Blood flow changes, reducing digestive system activity supressed and urine output Metabolic rate increases 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 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 (α) cells produce glucagon (hyperglycemic hormone) Beta (β) cells produce insulin (hypoglycemic hormone) Figure 16.18 Photomicrograph of differentially stained pancreatic tissue. Pancreatic islet α (Glucagon- producing) cells β (Insulin- producing) cells Pancreatic acinar cells (exocrine) 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 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 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 Liver glucose falls to normal range. Stimulus Blood glucose level Stimulus Blood glucose level Blood glucose rises to normal range. Pancreas Glucose Glycogen Liver Stimulates glycogen Glucagon breakdown 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