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Chapter 16: The Endocrine System The Endocrine System • Endocrinology – Study of hormones and endocrine organs • Acts with nervous system to coordinate and integrate activity of body cells • Influences metabolic activities via hormones transported via bloodstream Two Types of Glands • Exocrine glands – Non-hormonal secretions (sweat, saliva) – Have ducts to carry secretion to membrane surface • Endocrine glands – Produce hormones – Lack ducts (ductless) Endocrine Glands • • • • • • • Pituitary Thyroid Parathyroid Adrenal Pineal glands Pancreas Gonads 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) © 2013 Pearson Education, Inc. The Messengers of the Endocrine System • Hormones – long-distance chemical signals that travel in blood or lymph • Two main classes – Amino acid-based hormones • Amino acid derivatives, peptides, and proteins – Steroids • Synthesized from cholesterol Mechanism of Action • Hormones alter target cell activity via Cellular Receptor – Alter plasma membrane permeability – membrane potential – Transcriptional activity of enzymes or other proteins – Activate or deactivate enzymes – Induce secretory pathway – Stimulate cell division Receptors Transmit Signals via Secondary Chemical Messengers Protein Hormone: • cAMP signaling mechanism • PIP2-calcium signaling mechanism – Phosphatidylinositol 4,5-bisphosphate Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones. Slide 6 Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger 1 Hormone (1st messenger) binds receptor. Extracellular fluid Adenylate cyclase G protein (Gs) Receptor 5 cAMP activates protein kinases. cAMP GTP GTP ATP GDP Inactive protein kinase GTP Active protein kinase Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 Receptor activates G protein (Gs). © 2013 Pearson Education, Inc. 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to cAMP (2nd messenger). PIP2-calcium signaling mechanism • Involves G protein and membrane-bound protein – phospholipase C (PLC) • Phospholipase C splits PIP2 into two second messengers – diacylglycerol (DAG) and inositol trisphosphate (IP3) • DAG activates PKC; IP3 causes Ca2+ release • Calcium ions act like a second messenger to continue the signal PIP2 IP3 Steroid Hormones 1. Diffuse into target cells and bind with intracellular receptors 2. Receptor-hormone complex enters nucleus; binds to specific region of DNA 3. Prompts DNA transcription to produce mRNA, promoting protein synthesis Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Extracellular fluid Steroid hormone Plasma membrane Cytoplasm Receptor protein Nucleus Slide 6 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. mRNA 5 The mRNA directs protein synthesis. New protein © 2013 Pearson Education, Inc. 3 Stimuli Events for Endocrine Secretion • Endocrine gland stimulated to synthesize and release hormones in response to – Humoral stimuli – Neural stimuli – Hormonal stimuli Humoral Stimuli • Changing blood levels of ions and nutrients directly stimulate secretion of hormones Neural Stimuli • Nerve fibers stimulate hormone release Hormonal Stimuli • Hormones stimulate other endocrine organs to release their hormones The Pituitary Gland and Hypothalamus • Pituitary gland (hypophysis) has two major lobes – Posterior (lobe) • Neural tissue – Anterior (lobe) (adenohypophysis) • Glandular tissue The Hypothalamus • Hypothalamus is neuroendocrine organ • Produces and secretes hormones • Regulates and can be regulated by other endocrine organs The Posterior Lobe and Hypothalamus • Downgrowth of hypothalamic neural tissue • Neural connection to hypothalamus (hypothalamic-hypophyseal tract) • Hypothalamus synthesize neurohormones oxytocin and antidiuretic hormone (ADH) – transported to and stored in posterior pituitary Figure 16.5a The hypothalamus controls release of hormones from the pituitary Slide 5 gland in two different ways (1 of 2). Paraventricular nucleus Hypothalamus Posterior lobe of pituitary Optic chiasma Infundibulum (connecting stalk) Hypothalamichypophyseal tract Supraoptic nucleus Inferior hypophyseal artery Axon terminals 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. Posterior lobe of pituitary Oxytocin ADH © 2013 Pearson Education, Inc. 1 Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH). 4 When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood. The Anterior Lobe of Pituitary • Vascular connection to hypothalamus – Hypophyseal portal system • Transport of releasing and inhibiting hormones created by the hypothalamus to the anterior pituitary to regulate additional hormone secretion Figure 16.5b The hypothalamus controls release of hormones from the pituitary Slide 4 gland in two different ways (2 of 2). Hypothalamus 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 © 2013 Pearson Education, Inc. Hypothalamic neurons synthesize GHRH, GHIH, TRH, CRH, GnRH, PIH. 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 A portal system is two capillary plexuses (beds) connected by veins. Hormones of Anterior Pituitary • Oxytocin and ADH (Antidiuretic Hormone) – peptide hormones Oxytocin • Strong stimulant of uterine contraction • Hormonal trigger for milk ejection • Acts as neurotransmitter in brain – sexual and affectionate behavior • “cuddle” hormone Antidiuretic Hormone (ADH) • Inhibits or prevents urine formation via regulating water balance • Hypothalamic neurons monitor solute concentration – Solute concentration too high (low water) • kidneys reabsorb more water ADH Regulation • Less water in urine, low urine output – more water in bloodstream resulting in lower solute concentrations • Feedback loop: – solute levels low, no ADH – solute levels high, ADH production AHD Deficiency • Diabetes insipidus – intense thirst and large urine output – due to hypothalamus or posterior pituitary damage • Note: Diseases/disorders caused by hyposecretion or hypersecretion of hormones Anterior Pituitary Hormones • Growth hormone (GH) • Thyroid-stimulating hormone (TSH) or thyrotropin • Adrenocorticotropic hormone (ACTH) • Follicle-stimulating hormone (FSH) • Luteinizing hormone (LH) • Prolactin (PRL) Anterior Pituitary Hormones • Protein hormones • All except GH activate cyclic AMP secondmessenger systems at their targets • TSH, ACTH, FSH, and LH are all tropic hormones – regulate secretory action of other endocrine glands GH Regulation • GH release regulated by hypothalamic hormones – Growth hormone–releasing hormone (GHRH) – Growth hormone–inhibiting hormone (GHIH) GH Biological Action • Indirect actions on growth – via insulin-like growth factors (IGFs) via IGFRs – bone and muscle growth • Direct actions on metabolism – Increases blood levels of fatty acids and stimulates use of fatty acids for fuel (fat loss) – Decreases rate of glucose uptake and metabolism (glucose conservation) Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH). Inhibits GHRH release Stimulates GHIH release Feedback Anterior pituitary Hypothalamus secretes growth hormone–releasing hormone (GHRH), and GHIH (somatostatin) Inhibits GH synthesis and release Growth hormone (GH) Indirect actions Direct actions (growthpromoting) (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 © 2013 Pearson Education, Inc. Increased fat breakdown and release Increased blood glucose and other anti-insulin effects Initial stimulus Physiological response Result Feedback inhibition • Hallmark regulatory mechanism • Inhibitory effect – Stimulus created – Production of signal (hormone) – Signal acts to stimulate desired outcome – Signal also acts to shut down stimulus that created signal to begin with The Thyroid Gland • Butterfly-shaped gland located in the front of the neck, on the trachea, under the larynx • The largest pure endocrine gland in body • Composed of hollow follicles formed by follicular cells • Produces Thyroid Hormone upon stimulation by Thyroid-stimulating hormone via anterior pituitary Inside the Thyroid • Follicular cells produce thyroglobulin • Follicles – filled with fluid of thyroglobulin + iodine • Parathyroid cells produce calcitonin Figure 16.9 The thyroid gland. Hyoid bone Thyroid cartilage Common carotid artery Epiglottis Colloid-filled follicles Follicular cells Superior thyroid 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 © 2013 Pearson Education, Inc. Photomicrograph of thyroid gland follicles (145x) Thyroid Hormone (TH) • Created by the cleavage of a thyroglobulin-iodine complex created in the lumen of follicle • Two iodine-bound amine hormones: – T4 (thyroxine); has 2 tyrosines + 4 bound iodine atoms – T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms Figure 16.10 Synthesis of thyroid hormone. Slide 8 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 ER Iodine 3 Iodide is oxidized to iodine. 2 Iodide (I–) is trapped (actively transported in). Iodide (I−) T4 T3 Lysosome DIT MIT Thyroglobulin colloid 5 Iodinated tyrosines are linked together to form T3 and T4. T4 T3 T4 T3 To peripheral tissues © 2013 Pearson Education, Inc. 6 Thyroglobulin colloid is endocytosed and combined with a lysosome. 7 Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream. Colloid in lumen of follicle Mechanism of T3/T4 synthesis T3 vs T4 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 TH Action • Body’s major metabolic hormone • Effects almost every cell in the body • Refer to Table 16.2 for major effects – basal metabolic rate and oxygen use – metabolism – growth and development – normal reproductive ability Figure 16.8 Regulation of thyroid hormone secretion. Hypothalamus TRH Thyrotropin releasing hormone Anterior pituitary TSH Thyrotropin stimulating hormone Thyroid gland Thyroid hormones Target cells © 2013 Pearson Education, Inc. Stimulates Inhibits The Parathyroid Glands • Tiny, yellow-brown glands in the posterior aspect of the thyroid gland • Two major cell types – oxyphil cells (function unknown) – parathyroid (chief) cells – secrete parathyroid hormone (PTH) or parathormone Figure 16.12 The parathyroid glands. Pharynx (posterior aspect) Capillary Thyroid gland Parathyroid glands Esophagus Trachea © 2013 Pearson Education, Inc. Parathyroid cells (secrete parathyroid hormone) Oxyphil cells Parathyroid Hormone • Most important hormone in Ca2+ homeostasis – Stimulates osteoclasts to digest bone matrix and release Ca2+ to blood – Enhances reabsorption of Ca2+ and secretion of phosphate (PO43-) by kidneys – Promotes activation of vitamin D (by kidneys) which is required for absorption of Ca2+ from food 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 © 2013 Pearson Education, Inc. Result PTH Calcium mechanism of Action • Ca2+ sensitive receptor (GPCR) binds to extracellular Ca2+ levels • Increased Ca2+ activates GPCR PLC activation via G protein intracellular Ca levels inhibition of secretory release of PTH (exocytosis) The Adrenal glands (Suprarenal) • Paired, pyramid-shaped organs on top of kidneys • Structurally and functionally two glands in one – Adrenal medulla – composed of nervous tissue – Adrenal cortex – encapsulates the medulla, composed of glandular tissue Adrenal Cortex • Composed of three layers that produce three different corticosteroids – Zona glomerulosa • produces mineralocorticoids – Zona fasciculata • produces glucocorticoids – Zona reticularis • produces gonadocorticoids Figure 16.14 Microscopic structure of the adrenal gland. Hormones secreted Zona glomerulosa Aldosterone Zona fasciculata Cortex Adrenal gland • Medulla • Cortex Capsule Cortisol and androgens Kidney Medulla Zona reticularis Adrenal medulla Drawing of the histology of the adrenal cortex and a portion of the adrenal medulla © 2013 Pearson Education, Inc. Epinephrine and norepinephrine Photomicrograph (115x) Mineralocorticoids (Aldosterone) • Regulate electrolytes in extracellular fluids – Na+ affects ECF volume, blood volume, blood pressure – where Na+ goes, so does water and other essential ions – K+ regulates resting membrane potential of all cells (RMP), actions potentials in nerve and muscle. Stimulation of Aldosterone • Release triggered by – Changes in blood volume and blood pressure – Rising blood levels of K+ – Stress • Aldosterone stimulates – reduces excretion of Na+ from body by stimulating Na+ (water) reabsorption – elimination of K+ Effect of Aldosterone • Increased absorption of Na+ • Increased secretion of K+ • Increased Blood pressure/blood volume The Renin-AngiotensinAldosterone Mechanism • BP/BV falls – kidneys release renin • Renin cleaves angiotensinogen (liver) • Activation of angiotensin II via cleavage. • Angiotensin II stimulates production of aldosterone at zona glomerulosa Increasing BP/BV • Atrial Natriuretic Peptide (ANP) secreted by heart • ANP inhibits renin and aldosterone secretion • Allows Na+ and water excretion Blood Concentration of K+ • Increased K+ levels directly stimulates aldosterone production at zona glomerulosa • Aldosterone promotes increased K+ excretion • Conversely, decreased K+ levels inhibits release of aldosterone Stress • Severe stress releases corticotrophin releasing hormone (CRH) from the hypothalamus • CRH increases adrenocorticotrophic hormone (ATCH) from pituitary gland • ATCH stimulates aldosterone secretion • Increase in blood volume/pressure Figure 16.15 Major mechanisms controlling aldosterone release from the adrenal cortex. Primary regulators Blood volume and/or blood pressure K+ in blood Other factors Stress Blood pressure and/or blood volume Hypothalamus Kidney Heart CRH Renin Direct stimulating effect Initiates cascade that produces Anterior pituitary Atrial natriuretic peptide (ANP) ACTH Angiotensin II Inhibitory effect Zona glomerulosa of adrenal cortex Enhanced secretion of aldosterone Targets kidney tubules Absorption of Na+ and water; increased K+ excretion © 2013 Pearson Education, Inc. Blood volume and/or blood pressure Zona fasciculata and Glucocorticoids • Steroid hormone • Influence energy metabolism of most body cells and help resist stressors • Help keep blood glucose constant during food intake • Maintain blood pressure by increasing action of vasoconstrictors Glucocorticoids • Major hormone is cortisol (hydrocortisone) • Action via regulating gene transcription • ACTH activates cortisol release (Pituitary) • Increasing cortisol inhibits CRH (hypothalamus)and corresponding ACTH release Cortisol Action • Prime metabolic effect is gluconeogenesis formation of glucose from fats and proteins – Promotes rises in blood glucose, fatty acids, and amino acids • Enhances vasoconstriction rise in blood pressure to quickly distribute nutrients to cells Glucocorticoids • Can control chronic inflammatory disorders – rheumatoid arthritis – allergic responses • Used for cancer therapy due to anti-inflammatory effects – combinatorial therapy • How much is too much, too little? – Cushing’s syndrome (too much) – Addison’s disease (too little) The Adrenal Medulla • Controlled by nervous system • Composed of medullary chromaffin cells that synthesize catecholamines – epinephrine (adrenaline) – norepinephrine The Adrenal Medulla • The stress response pathway (fight or flight status) • Effects – Vasoconstriction – Increased heart rate – Increased blood glucose levels – Blood diverted to brain, heart, and skeletal muscle Figure 16.17 Stress and the adrenal gland. Short-term stress Prolonged stress Stress Nerve impulses Hypothalamus CRH (corticotropinreleasing hormone) Spinal cord Corticotropic cells of anterior pituitary To target in blood 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 © 2013 Pearson Education, Inc. ACTH Mineralocorticoids Adrenal cortex (secretes steroid hormones) Glucocorticoids Long-term stress response • Kidneys retain • Proteins and fats converted sodium and water to glucose or broken down for energy • Blood volume and • Blood glucose increases blood pressure • Immune system rise supressed Short term vs Long term Stress • Short term – Action via preganglionic sympathtic fibers to Adrenal medulla to secrete catecholamines • Long term – Action via hypothalamus to anterior pituitary to Adrenal cortex to secrete mineralocorticoids and glucocorticoids Pineal Gland Tiny, pine cone-shaped gland that hangs from the roof of the third ventricle in the brain Function still a mystery Major peptide hormone is malatonin The Pineal Gland • Secretory cells called pinealocytes – secrete melatonin • 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, elongated gland partially behind stomach • Has both exocrine and endocrine cells • Acinar cells form the bulk of the gland • Scattered throughout are clusters of Pancreatic islets (islets of Langerhans) Pancreas Histology • Acinar Cells (exocrine function) – secrete enzyme rich juice to small intestines to aid in digestion • Pancreatic islets (endocrine function) • Alpha () cells produce glucagon (hyperglycemic hormone) • Beta () cells produce insulin (hypoglycemic hormone) Figure 16.18 Photomicrograph of differentially stained pancreatic tissue. Pancreatic islet • (Glucagonproducing) cells • (Insulinproducing) cells Pancreatic acinar cells (exocrine) © 2013 Pearson Education, Inc. Glucagon • Produced by alpha cells • Major target—liver • Causes increased blood glucose levels – Glycogenolysis—breakdown of glycogen to glucose – Gluconeogenesis—synthesis of glucose from lactic acid and other biomolecules – Release of glucose to blood 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 Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels. Stimulates glucose uptake by cells Tissue cells Insulin Stimulates glycogen formationw Pancreas Glucose Glycogen Blood glucose falls to normal range. Liver Stimulus Blood glucose level Stimulus Blood glucose level Blood glucose rises to normal range. Pancreas Glucose Glycogen Liver © 2013 Pearson Education, Inc. Stimulates glycogen breakdown Glucagon Other organs and hormone secretion • • • • • • • Gonads (Ch. 27) Adipose Tissue GI tract (Ch. 23) Heart (Chps. 18 and 19) Kidneys (Ch. 25) Skeleton Skin Today’s Lab • Lab Exercise 27 – Read Objectives of the exercise • The introduction of the lab is a repeat of the lecture but will serve as a useful guide to completing the assignment