Chapter 19 The Peripheral Endocrine Glands Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Peripheral Endocrine Glands • Outline • Thyroid glands – Anatomy and hormones • Adrenal glands – Anatomy and hormones – Stress response • Fuel metabolism • Calcium metabolism Thyroid Gland • Consists of two lobes of endocrine tissue joined in middle by narrow portion of gland • Follicular cells – Arranged into hollow spheres – Forms functional unit called a follicle – Lumen filled with colloid • Serves as extracellular storage site for thyroid hormone – Produce two iodine-containing hormones derived from amino acid tyrosine • Tetraiodothyronine (T4 or thyroxine) • Tri-iodothyronine (T3) • C cells – Secrete peptide hormone calcitonin Thyroid Gland Fig. 19-1b, p. 684 Fig. 19-2, p. 685 Thyroid hormone synthesis • • • • • Tg = thyroglobulin Transport of Tg to colloid Iodine uptake to colloid Iodination of tyrosine coupling Thyroid hormone release • Stored as Tg • Phagocytes “bite” Tg containing colloid • Phagocytes cleave T3 and T4 from Tg in the follicular cells • T3 and T4 diffuse to blood (TBG carrier protein in blood) • Iodine is recycled after metabolism • Activity – 90% T4 but T3 4X aspotent Colloid Blood Thyroid follicular cell *Endoplasmic reticulum/Golgi complex Lysosome TGB = Thyroglobulin I = Iodine MIT = Monoiodotyrosine DIT = Di-iodotyrosine T3 = Tri-iodothyronine T4 = Tetraiodothyronine (thyroxine) Fig. 19-2, p. 685 Thyroid Gland • Effects of thyroid hormone – Main determinant of basal metabolic rate and heat production – Influences synthesis and degradation of carbohydrate, fat, and protein (intermediary metabolism) – Increases target-cell responsiveness to catecholamines (sympathomimetic effect) – Increases heart rate and force of contraction – Essential for normal growth – Plays crucial role in normal development of skeleton and nervous system (stimulates GH and IGF-1) Thyroid Gland • Secretion – Regulated by negative-feedback system between hypothalamic TRH, anterior pituitary TSH, and thyroid gland T3 and T4 – Feedback loop maintains thyroid hormones relatively constant Stress Cold in infants Hypothalamus Thyrotropinreleasing hormone (TRH) Anterior pituitary Thyroid-stimulating hormone (TSH) Thyroid gland Thyroid hormone (T3 and T4) Metabolic rate and heat production; enhancement of growth and CNS development; enhancement of sympathetic activity Fig. 19-3, p. 687 Thyroid Gland Dysfunction Table 19-1, p. 687 Thyroid Gland • Abnormalities – Hyperthyroidism • Most common cause is Graves’ disease – Autoimmune disease – Body erroneously produces thyroid-stimulating immunoglobulins (TSI) – Characterized by exopthalmos • Treatment – Surgical removal of a portion of the over-secreting thyroid – Administration of radioactive iodine – Use of antithyroid drugs Graves disease Antibody that binds TSH receptors no negative FB Fig. 19-4, p. 688 Hyperthyroidism - exopthalmos Fig. 19-5, p. 688 Thyroid Gland • Abnormalities – Hypothyroidism • Causes – Primary failure of thyroid gland – Secondary to a deficiency of TRH, TSH, or both – Inadequate dietary supply of iodine • Cretinism – Results from hypothyroidism from birth • Myxedema – Term often used for myxedema in adults • Treatment – Replacement therapy – Dietary iodine Hypothyroidism Goiter Fig. 19-6, p. 689 Adrenal Glands • Embedded above each kidney in a capsule of fat • Composed of two endocrine organs – Adrenal cortex • Outer portion • Secretes steroid hormones – Adrenal medulla • Inner portion • Secretes catecholamines Adrenal cortex Anatomy Adrenal medulla Zona glomerulosa Cortex Zona fasciculata (See next slide) Zona reticularis Medulla Adrenal gland (C) Brooks/Cole - Thomson Learning Fig. 19-7, p. 690 Adrenal Glands Zona glomerulosa Zona fasciculata (See next slide) Zona reticularis • Adrenal cortex – Consists of three layers or zones • Zona glomerulosa – outermost layer (Mineralocorticoids) Medulla • Zona fasciculata – middle and largest portion (Glucocorticoids) • Zona reticularis – innermost zone (Sex hormones) – Categories of adrenal steroids • Mineralocorticoids – Mainly aldosterone – Influence mineral balance, specifically Na+ and K+ balance • Glucocorticoids – Primarily cortisol – Major role in glucose metabolism as well as in protein and lipid metabolism • Sex hormones – Identical or similar to those produced by gonads – Most abundant and physiologically important is dehydroepiandosterone (male “sex” hormone) Connective tissue capsule Zona glomerulosa Zona fasciculata Cortex Zona reticularis Medulla Fig. 19-7, p. 690 Cholesterol Pregnenolone Progesterone Zona glomerulosa Corticosterone Aldosterone Cholesterol Pregnenolone 17-OH-Pregnenolone Zona fasciculata 17-OH-Progesterone Cortisol Cholesterol Pregnenolone Zona reticularis 17-OH-Pregnenolone fig 14-5, pg 437 Dehydroepiandrosterone Effects of Adrenal Cortical Hormones • Permissive actions on catecholamines • Stress adaptation (releases building blocks of new tissue) • Anti-inflamatory and immunosuppressive Regulation of cortisol • ACTH from POMC • Negative feedback Diurnal rhythm Stress Hypothalamus Corticotropin-releasing hormone (CRH) Anterior pituitary Adrenocorticotropic hormone (ACTH) Adrenal cortex Cortisol Metabolic fuels and building blocks available to help resist stress Blood glucose (by stimulating gluconeogenesis and inhibiting glucose uptake) Blood amino acids (by stimulating protein degradation) Blood fatty acids (by stimulating lipolysis) Fig. 19-8, p. 692 Adrenal Glands • Cortisol • Zona fasciculata – middle and largest portion (Glucocorticoids) – Stimulates hepatic gluconeogenesis – Inhibits glucose uptake and use by many tissues, but not the brain – Stimulates protein degradation in many tissues, especially muscle – Facilitates lipolysis – Plays key role in adaptation to stress – At pharmacological levels, can have anti-inflammatory and immunosuppressive effects • Long-term use can result in unwanted side effects – Displays a characteristic diurnal rhythm (day hi night low) – Secretion • Regulated by negative-feedback loop involving hypothalamic CRH and pituitary ACTH Adrenal Glands • Secretes both male and female sex hormones in both sexes – Dehydroepiandrosterone (DHEA) • Zona reticularis – innermost zone (Sex hormones) • Only adrenal sex hormone that has any biological importance • Overpowered by testicular testosterone in males • Physiologically significant in females where it governs – Growth of pubic and axillary hair – Enhancement of pubertal growth spurt – Development and maintenance of female sex drive Hypothalamus GnRH CRH Anterior pituitary FSH, LH ACTH Gonads Adrenal cortex Enzyme absent No sex hormone production No gamete (androgens or estrogens) production Androgen No cortisol Virilization = Normal pathway that does not occur FSH = Follicle-stimulating hormone ACTH = Adrenocorticotropic hormone LH = Luteinizing hormone GnRH = Gonadotropin-releasing hormone CRH = Corticotropin-releasing hormone Fig. 19-10, p. 695 Adrenal Glands • Aldosterone • Zona glomerulosa – outermost layer (Mineralocorticoids) – Secretion is increased by • Activation of renin-angiotensin-aldosterone system by factors related to a reduction in Na+ and a fall in blood pressure • Direct stimulation of adrenal cortex by rise in plasma K+ concentration – Regulation of aldosterone secretion is largely independent of anterior pituitary control Disorders of Adrenocortical Function • Aldosterone hypersecretion – Primary hyperaldosteronism or Conn’s syndrome • Cortisol hypersecretion – Cushings syndrome • Adrenal androgen hypersecretion – Hirutism, female pseudohermaphrodism, precosious pseudopuberty • Primary adrenocortical insuficiency – Addison’s disease Disorders of Adrenocortical Function • Aldosterone hypersecretion – May be caused by • Hypersecreting adrenal tumor made up of aldosteronesecreting cells – Primary hyperaldosteronism or Conn’s syndrome • Inappropriately high activity of the renin-angiotensin system – Secondary hyperaldosteronism – Symptoms • Excessive Na+ retention and K+ depletion • High blood pressure Disorders of Adrenocortical Function • Cortisol hypersecretion – Cushing’s syndrome – Causes • Overstimulation of adrenal cortex by excessive amounts of CRH and ACTH • Adrenal tumors that uncontrollably secrete cortisol independent of ACTH • ACTH-secreting tumors located in places other than the pituitary – Signs and symptoms • Hyperglycemia and glucosuria (adrenal diabetes) • Abnormal fat distributions – “buffalo hump” and “moon face” Fig. 19-9, p. 694 Disorders of Adrenocortical Function • Adrenal androgen hypersecretion – Adrenogenital syndrome – Symptoms • Adult females – Hirsutism – Deepening of voice, more muscular arms and legs – Breasts become smaller and menstruation may cease • Newborn females – Have male-type external genitalia • Prepubertal males – Precocious pseudopuberty • Adult males – Has no apparent effect Disorders of Adrenocortical Function • Adrenocortical insufficiency – Primary adrenocortical insufficiency • Addison’s disease • Autoimmune disease – Aldosterone deficiency » Hyperkalemia and hyponatremia – Cortisol deficiency » Poor response to stress » Hypoglycemia » Lack of permissive action for many metabolic activities – Secondary adrenocortical insufficiency • Occurs because of pituitary or hypothalamic abnormality • Only cortisol is deficient Adrenal Medulla • Modified part of sympathetic nervous system • Primary stimulus for increased adrenomedullary secretion activation of sympathetic nervous system by stress • Releases epinephrine and norepinephrine – Secreted into blood by exocytosis of chromaffin granules – Vary in their affinities for the different adrenergic receptor types • Epinephrine – Reinforces sympathetic system in mounting general systemic “fight-or-flight” responses – Maintenance of arterial blood pressure – Increases blood glucose and blood fatty acids Table 19-2, p. 697 CNS Receptor type target cells PNS Somatic Preganglionic Postaganglionic Autonomic sympathetic Autonomic sympathetic Autonomic paraysmpathetic Brainstem Autonomic parasympathetic Nicotinic Alpha-receptors Beta receptors Muscarinic Norephinephrine Epinephrine Acetylcholine Nicotinic Somatic alpha-motor neuron Adrenal gland Skeletal muscle NE (15%) Thoracic E (85%) Autonomic sympathetic Alpha Blood stream Chromaffin cell Sympathetic ANS Beta Autonomic sympathetic Sacral Ganglia Muscarinic Autonomic parasympathetic Parasympathetic ANS fig 10-6, pg 343 Stress Response • Pattern of reactions to a situation that threatens homeostasis • Stress – Generalized nonspecific response of body to any factor that overwhelms or threatens to overwhelm the body’s ability to maintain homeostasis • Stressor – Any noxious stimulus that brings about the stress response Shivering, fever, inflammation, etc. General adaptation syndrome Fig. 19-11, p. 698 General Adaptation Syndrome • Alarm reaction- fight or flight response,muscles tense, HR and BP increase • Resistance or adaptation-nervous and endocrine systems deal with stressor. dangerous if long term. • Exhaustion-resistance drops, immunity suppression, depletion of energy reserves, stress related disease. Stress Response • All the actions are coordinated by the hypothalamus • Generalized stress response – Activation of sympathetic nervous system accompanied by epinephrine secretion • Prepares body for fight-or-flight response – Activation of CRH-ACTH-cortisol system • Helps body cope by mobilizing metabolic resources – Elevation of blood glucose and fatty acids • Decreased insulin and increased glucagon secretion – Maintenance of blood volume and blood pressure • Increased activity of renin-angiotensin-aldosterone system and increased vasopressin secretion Stressor Hypothalamus CRH Sympathetic nervous system Posterior pituitary Anterior pituitary ACTH Vasopressin Adrenal medulla Adrenal cortex Epinephrine Cortisol Glucagon-secreting cells Insulin-secreting cells Arteriolar Endocrine pancreas smooth muscle Vasoconstriction Glucagon Insulin Blood flow through kidneys Renin Angiotensin Aldosterone Fig. 19-12, p. 700 Table 19-3, p. 699 Endocrine Control of Fuel Metabolism • Metabolism – All the chemical reactions that occur within the cells of the body • Intermediary metabolism or fuel metabolism – Includes reactions involving the degradation, synthesis, and transformation of proteins, carbohydrates, and fats • Nutrient molecules are broken down through the process of digestion into smaller absorbable molecules – Proteins → amino acids – Carbohydrates → monosaccharides (mainly glucose) – Dietary fats (triglycerides) → monoglycerides and free fatty acids Table 19-4, p. 701 Anabolism and Catabolism • Anabolism – Buildup or synthesis of larger organic macromolecules from small organic subunits – Reactions usually require ATP energy – Reactions result in • Manufacture of materials needed by the cell • Storage of excess ingested nutrients not immediately needed for energy production or needed as cellular building blocks • Catabolism – Breakdown or degradation of large, energy-rich organic molecules within cells – Two levels of breakdown • Hydrolysis of large cellular molecules into smaller subunits • Oxidation of smaller subunits to yield energy for ATP production Food intake Dietary protein Dietary carbohydrate Dietary triglyceride fat D I G E S T I O N Absorbable units Amino acids Glucose Fatty acids Monoglycerides A B S O R P T I O N Metabolic pool in body Body proteins (structural or secretory products) Storage, structural, and functional macromolecules in cells Amino acids Glycogen storage in liver and muscle Glucose Triglycerides in adipose tissue stores (fat) Fatty acids Urea Urinary excretion (elimination from body) Oxidation to CO2 + H2O + ATP (energy) Expired (elimination from body) Use as metabolic fuel in cells Fig. 19-13, p. 702 Interconversions Among Organic Molecules • Most interconversion of organic molecules occurs in liver • Essential nutrients (certain amino acids and vitamins) • Food intake is intermittent – nutrients must be stored for use between meals – Excess circulating glucose • Stored in liver and muscle as glycogen • Once liver and muscle stores are “filled up”, additional glucose is transformed into fatty acids and glycerol and stored in adipose tissue – Excess circulating fatty acids • Become incorporated into triglycerides – Excess circulating amino acids • Converted to glucose and fatty acids Stored Metabolic Fuel in the Body Metabolic States • Absorptive state – Fed state – Glucose is plentiful and serves as major energy source • Postabsorptive state – Fasting state – Endogenous energy stores are mobilized to provide energy Roles of Key Tissues in Metabolic States • Liver – Primary role in maintaining normal blood glucose levels – Principal site for metabolic interconversions such as gluconeogenesis • Adipose tissue – Primary energy storage site – Important in regulating fatty acid levels in the blood • Muscle – Primary site of amino acid storage – Major energy user • Brain – Normally can only use glucose as an energy source – Does not store glycogen • Mandatory blood glucose levels be maintained Pancreas Alpha cell Beta cell Delta cell Capillaries Fig 15-3, pg 455 Pancreatic Hormones • Pancreas – Endocrine cells – Islets of Langerhans • Β (beta) cells – Site of insulin synthesis and secretion • Α (alpha) cells – Produce glucagon • D (delta) cells – Pancreatic site of somatostatin synthesis • PP cells – Least common islet cells – Secrete pancreatic polypeptide – The function of PP is to self regulate the pancreas secretion activities (endocrine and exocrine). • Insulin and glucagon – Most important in regulating fuel metabolism Pancreatic Hormones • Somatostatin – Released from pancreatic D cells in direct response to increase in blood sugar and blood amino acids during absorption of a meal – Prevents excessive plasma levels of nutrients – Local presence of somatostatin decreases secretion of insulin, glucagon, and somatostatin itself – Physiologic importance has not been determined – somatomedin • A peptide hormone (4 kD) that is produced in the liver and is released in response to growth hormone. Somatomedin stimulates the growth of bone and muscle. Pancreatic Hormones • Insulin – Anabolic hormone – Promotes cellular uptake of glucose, fatty acids, and amino acids and enhances their conversion into glycogen, triglycerides, and proteins, respectively • Lowers blood concentration of these small organic molecules – Secretion is increased during absorptive state • Primary stimulus for secretion is increase in blood glucose concentration Diabetes Mellitus • Most common of all endocrine disorders • Prominent feature is elevated blood glucose levels – Urine acquires sweetness from excess blood glucose that spills into urine • Two major types – Type I diabetes • Characterized by lack of insulin secretion – Type II diabetes • Characterized by normal or even increased insulin secretion but reduced sensitivity of insulin’s target cells Comparison of Type I and Type II Diabetes Acute Effects of Diabetes Mellitus Pancreatic Hormones • Glucagon – Mobilizes energy-rich molecules from storage sites during postabsorptive state – Secreted in response to a direct effect of a fall in blood glucose on pancreatic α cells – Generally opposes actions of insulin – No known clinical abnormalities caused by glucagon deficiency or excess • Excess of glucose can aggravate hyperglycemia of diabetes mellitus Endocrine Control of Calcium Metabolism • Plasma Ca2+ must be closely regulated to prevent changes in neuromuscular excitability – Also plays vital role in a number of essential activities • • • • • Excitation-contraction coupling in cardiac and smooth muscle Stimulus-secretion coupling Maintenance of tight junctions between cells Clotting of blood Neurotransmitter release – Hypercalcemia • Reduces excitability – Hypocalcemia • Brings about overexcitability of nerves and muscles • Severe overexcitability can cause fatal spastic contractions of respiratory muscles Endocrine Control of Calcium Metabolism • Three hormones regulate plasma concentration of Ca2+ (and PO43-) – Parathyroid hormone (PTH) – Calcitonin – Vitamin D Endocrine Control of Calcium Metabolism • Calcitonin – Hormone produced by C cells of thyroid gland – Negative-feedback fashion • Secreted in response to increase in plasma Ca2+ concentration – Acts to lower plasma Ca2+ levels by inhibiting activity of bone osteoclasts – Unimportant except during hypercalcemia Endocrine Control of Calcium Metabolism • Parathyroid hormone (PTH) – Secreted by parathyroid glands – Primary regulator of Ca2+ • Raises free plasma Ca2+ levels by its effects on bone kidneys, and intestines – Essential for life • Prevents fatal consequences of hypocalcemia – Facilitates activation of Vitamin D Endocrine Control of Calcium Metabolism • Vitamin D – Stimulates Ca2+ and PO43- absorption from intestine – Can be synthesized from cholesterol derivative when exposed to sunlight • Often inadequate source – Amount supplemented by dietary intake – Must be activated first by liver and then by kidneys before it can exert its effect on intestines Calcium Disorders • PTH hypersecretion (hyperparathyroidism) – Characterized by hypercalcemia and hypophosphatemia • PTH hyposecretion (hypoparathyroidism) – Characterized by hypocalcemia and hyperphosphatemia • Vitamin D deficiency – Children – rickets – Adults – osteomalacia Precursor in skin (7-dehydrocholesterol) Dietary vitamin D Sunlight Vitamin D3 Hydroxyl group (OH) Liver enzymes 25-OH D3 PTH Hydroxyl group + Plasma Ca2+ Kidney enzymes Plasma PO4 3- 1, 25-(OH)2 D3 (active vitamin D) Promotes intestinal absorption of Ca2+ and PO4 3- Fig. 19-23, p. 723 Credit: © Mediscan/Visuals Unlimited Rickets is a condition caused by a deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanels, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functional. 206184 Negative-feedback Loops Controlling Parathyroid Hormone (PTH) and Calcitonin Secretion Bone remodeling • Bone deposition • Bone resorption • Osteoblasts – secrete matrix for calcium phosphate – Stromal cells • Osteocytes – retired osteoblasts • Osteoclasts – resorb bone – macrophages – Acids breakdown calcium phosphate and matrix – RANKL – accelerates osteoclast activity – OPG – suppresses osteoclast activity and development Fig. 19-19, p. 718 Osteoporosis • Bone thinning • Increased osteoclast activity • Reduced osteoblast activity Osteoporosis from an 89 year-old female. SEM. Endocrine Control of Calcium Metabolism • Vitamin D – Stimulates Ca2+ and PO43- absorption from intestine – Can be synthesized from cholesterol derivative when exposed to sunlight • Often inadequate source – Amount supplemented by dietary intake – Must be activated first by liver and then by kidneys before it can exert its effect on intestines Blood glucose Blood glucose cell cell cell cell Glucagon Insulin Glucagon Insulin Blood glucose to normal Blood glucose to normal Fig. 19-17, p. 713 Table 19-7b, p. 715 Table 19-8, p. 717 Central canal Osteocyte Lamella Canaliculi Osteon Blood vessel from marrow Central canal Vessel in central canal Stepped art Fig. 19-20, p. 719 Fig. 19-21a, p. 722 Osteocyte Osteoblast Osteocytic– osteoblastic bone membrane Osteoblast Mineralized bone Outer surface Blood vessel Central canal Bone fluid Canaliculi Lamellae Fig. 19-21a, p. 722 Fig. 19-21b, p. 722 Relieves Plasma PO43- (Because of inverse relationship between plasma PO43- and Ca2+ concentrations caused by solubility characteristics of calcium phosphate salt) Plasma Ca2+ Kidneys Parathyroid glands Activated vitamin D PTH PO43- reabsorption by kidneys Ca2+ reabsorption by kidneys Urinary excretion of Ca2+ Ca2+ absorption in intestine (Counteract each other) Urinary excretion of PO43- No change in plasma Ca2+ PO43- absorption in intestine Plasma PO43Fig. 19-25, p. 725