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Human Physiology – From Cells to Systems | 9e Lauralee Sherwood 19 The Peripheral Endocrine Glands © Cengage Learning 2016 2016. All Rights Reserved. 19.1 Thyroid Gland • The major cells that secrete thyroid hormone are organized into colloid-filled follicles – Interspersed in the interstitial spaces between follicles are C cells, which secrete calcitonin • Thyroid hormone is synthesized and stored on the thyroglobulin molecule – Most steps of thyroid hormone synthesis take place on the thyroglobulin molecules within the colloid © Cengage Learning 2016. All Rights Reserved. Thyroid follicular cell Blood Colloid Golgi complex Endoplasmic reticulum I– MIT Tg DIT I– I– TPO Active I– (Deiodinase action) I– I– Lysosome MIT DIT T3 T4 MIT DIT T3 , T4 Tg MIT DIT T3 T4 1 MIT 2 DITs 1 DIT T3 T T3 4 T4 Thyroid follicle KEY = Primary active transport = Secondary active transport (symporter) Tg = Thyroglobulin I– = Iodide TPO = Thyroperoxidase MIT = Monoiodotyrosine Tyrosine-containing Tg produced within the thyroid follicular cells by the endoplasmic reticulum–Golgi complex is transported by exocytosis into the colloid. Iodide is carried by secondary active transport from the blood into the colloid by symporters in the basolateral membrane of the follicular cells. In the follicular cell, the iodide is oxidized to active form by TPO at the luminal membrane. DIT = Di-iodotyrosine T3 = Tri-iodothyronine T4 = Tetraiodothyronine (thyroxine) Attachment of two iodides to tyrosine yields DIT. Coupling of one MIT and one DIT yields T3. Coupling of two DITs yields T4. On appropriate stimulation, the thyroid follicular cells engulf a portion of Tg-containing colloid by phagocytosis. Lysosomes attack the engulfed vesicle and split the iodinated products from Tg. The active iodide exits the cell through a luminal channel to enter the colloid. T3 and T4 diffuse into the blood (secretion). Catalyzed by TPO, attachment of one iodide to tyrosine within the Tg molecule yields MIT. MIT and DIT are deiodinated, and the freed iodide is recycled for synthesizing more hormone. © Cengage Learning 2016. All Rights Reserved. Thyroid Hormone Secretions • To secrete thyroid hormone, the follicular cells phagocytize thyroglobulin-laden colloid – Thyroxine-binding globulin: a plasma protein that selectively binds only thyroid hormone • Transports most circulating T4 and T3 – About 90% of the secretory product released from the thyroid gland is in the form of T4 • Most is converted into T3 © Cengage Learning 2016. All Rights Reserved. Effects of Thyroid Hormone • Thyroid hormone increases the basal metabolic rate and exerts other effects – Effect on metabolic rate and heat production • Increases the body’s overall basal metabolic rate • Calorigenic effect: “heat-producing” – Sympathomimetic effect • Any action similar to one produced by the sympathetic nervous system © Cengage Learning 2016. All Rights Reserved. Effects of Thyroid Hormone (cont’d.) – Effect on the cardiovascular system • Increased heart rate, force of contraction, and cardiac output – Effect on growth and the nervous system • Stimulates GH secretion, increases production of IGF-I by the liver, and promotes GH and IGF-I effects on the synthesis of new structural proteins and on bone growth © Cengage Learning 2016. All Rights Reserved. Hypothalamus–Pituitary–Thyroid axis • Thyroid hormone is regulated by the hypothalamus–pituitary–thyroid axis – Most important regulator of thyroid hormone secretion • Abnormalities of thyroid function include both hypothyroidism and hyperthyroidism – Hypothyroidism: thyroid hormone secretion deficiency – Hyperthyroidism: thyroid hormone secretion excess © Cengage Learning 2016. All Rights Reserved. © Cengage Learning 2016. All Rights Reserved. Goiter • A goiter develops when the thyroid gland is overstimulated – Enlarged thyroid gland – Readily palpable and usually highly visible – Occurs whenever either TSH or TSI excessively stimulates the thyroid gland – May accompany hypothyroidism or hyperthyroidism © Cengage Learning 2016. All Rights Reserved. 19.2 Adrenal Glands • Each adrenal gland consists of a steroidsecreting cortex and a catecholaminesecreting medulla – Secrete hormones belonging to different chemical categories • The adrenal cortex secretes mineralocorticoids, glucocorticoids, and sex hormones – Layers: zona glomerulosa, zona fasciculata, and zona reticularis © Cengage Learning 2016. All Rights Reserved. Mineralocorticoids • The major effects of mineralocorticoids are on Na+ and K+ balance and blood pressure homeostasis – Aldosterone promotes Na + retention and enhances K + elimination during the formation of urine • Mineralocorticoids are essential for life • Without aldosterone, a person rapidly dies from circulatory shock © Cengage Learning 2016. All Rights Reserved. Glucocorticoids • Glucocorticoids exert metabolic effects and play a key role in adaptation to stress – Metabolic effects – Permissive actions – Role in adaptation to stress – Anti-inflammatory and immunosuppressive effects © Cengage Learning 2016. All Rights Reserved. Cortisol Secretion • Cortisol secretion is regulated by the hypothalamus–pituitary–adrenal cortex axis – Regulated through a negative-feedback system involving the hypothalamus and anterior pituitary • The adrenal cortex secretes both male and female sex hormones in both sexes – Androgens and estrogens © Cengage Learning 2016. All Rights Reserved. Adrenal Cortex • The adrenal cortex may secrete too much or too little of any of its hormones – Aldosterone hypersecretion – Cortisol hypersecretion – Adrenal androgen hypersecretion – Adrenocortical insufficiency © Cengage Learning 2016. All Rights Reserved. Adrenal Medulla • The adrenal medulla consists of modified sympathetic postganglionic neurons – Secretion of catecholamines from the adrenal medulla • Catecholamines are secreted into the blood by exocytosis of chromaffin granules • Epinephrine and norepinephrine vary in their affinities for different receptor types – Norepinephrine binds predominantly with ᾳ and β1 receptors © Cengage Learning 2016. All Rights Reserved. Epinephrine • Epinephrine reinforces the sympathetic nervous system and exerts metabolic effects – Effects on organ systems: increases cardiac output and dilates respiratory airways – Metabolic effects: prompts mobilization of stored carbohydrate and fat so extra energy is available as needed to fuel muscular work – Other effects: promotes arousal, increases alertness, causes sweating, etc. © Cengage Learning 2016. All Rights Reserved. Epinephrine (cont’d.) • Epinephrine is released only on sympathetic stimulation of the adrenal medulla – Catecholamine secretion by the adrenal medulla is controlled entirely by sympathetic input to the gland – Amount of epinephrine released depends on the type and intensity of the stressful stimulus © Cengage Learning 2016. All Rights Reserved. 19.3 Integrated Stress Response • The stress response is a generalized pattern of reactions to any situation that threatens homeostasis – Roles of the sympathetic nervous system and epinephrine in stress – Roles of the CRH–ACTH–cortisol system in stress – Role of other hormonal responses in stress © Cengage Learning 2016. All Rights Reserved. Stressor Specific response characteristic of type of stressor Body © Cengage Learning 2016. All Rights Reserved. Nonspecific generalized response regardless of type of stressor = Stress response Stressor Hypothalamus Posterior pituitary CRH Anterior pituitary Sympathetic nervous system Vasopressin ACTH Conserve salt and H2O to expand the plasma volume; help sustain blood pressure when acute loss of plasma volume occurs Vasopressin and angiotensin II cause arteriolar vasoconstriction to increase blood pressure Adrenal cortex Adrenal medulla Epinephrine Cortisol Prepare body for “fight or flight” Arteriolar smooth muscle Glucagon-secreting cells Insulin-secreting cells Endocrine pancreas Vasoconstriction Blood flow through kidneys Glucagon Renin Angiotensin Aldosterone © Cengage Learning 2016. All Rights Reserved. Insulin Mobilize energy stores and metabolic building blocks for use as needed Integrated Stress Response • The multifaceted stress response is coordinated by the hypothalamus – Receives input concerning physical and emotional stressors from virtually all areas of the brain and many receptors – Directly activates sympathetic nervous system • Activation of the stress response by chronic psychosocial stressors may be harmful © Cengage Learning 2016. All Rights Reserved. 19.4 Endocrine Pancreas and Control of Fuel Metabolism • Fuel metabolism includes anabolism, catabolism, and interconversions among energy-rich organic molecules – Anabolism: buildup of large organic macromolecules from small organic subunits – Catabolism: breakdown of large, energy-rich organic molecules within cells – Interconversions among organic molecules: most small organic molecules can be converted into other types © Cengage Learning 2016. All Rights Reserved. © Cengage Learning 2016. All Rights Reserved. Endocrine Pancreas and Control of Fuel Metabolism • Because food intake is intermittent, nutrients must be stored for use between meals – Energy storage forms: excess circulating glucose, circulating fatty acids, and circulating amino acids • The brain must be continuously supplied with glucose – Sole source of energy © Cengage Learning 2016. All Rights Reserved. Metabolic Fuels • Metabolic fuels are stored during the absorptive state and mobilized during the postabsorptive state – Absorptive state: occurs after a meal – Postabsorptive state: occurs between meals – Roles of key tissues in metabolic states: the liver, adipose tissue, muscle, and brain © Cengage Learning 2016. All Rights Reserved. Fuel Metabolism • Lesser energy sources are tapped as needed – Glycerol, lactate, and ketone bodies • The pancreatic hormones, insulin and glucagon, are most important in regulating fuel metabolism – Islets of Langerhans: endocrine cells scattered throughout the pancreas – Somatostatin: inhibits the digestive system © Cengage Learning 2016. All Rights Reserved. Insulin • Insulin lowers blood glucose, fatty acid, and amino acid levels and promotes their storage – Actions on carbohydrates – Actions on fat – Actions on protein – Summary of insulin’s actions – Role of amylin © Cengage Learning 2016. All Rights Reserved. Factors that increase blood glucose Factors that decrease blood glucose Transport of glucose into cells: ––For utilization for energy production ––For storage as glycogen through glycogenesis as triglycerides Glucose absorption from digestive tract Blood glucose Hepatic glucose production: ––Through glycogenolysis of stored glycogen ––Through gluconeogenesis KEY = Factors subject to hormonal control to maintain blood glucose level © Cengage Learning 2016. All Rights Reserved. Urinary excretion of glucose (occurs only abnormally, when blood glucose level becomes so high it exceeds the reabsorptive capacity of kidney tubules during urine formation) Blood Glucose • The primary stimulus for increased insulin secretion is an increase in blood glucose – The primary control of insulin secretion is a direct negative-feedback system between pancreatic β cells and concentration of glucose in the blood flowing to them – Glucose stimulates insulin secretion by means of an excitation–secretion coupling process © Cengage Learning 2016. All Rights Reserved. Symptoms of Diabetes M ellitus • The symptoms of diabetes mellitus are characteristic of an exaggerated postabsorptive state – Consequences related to effects on carbohydrate metabolism – Consequences related to effects on fat metabolism – Consequences related to effects on protein metabolism – Long-term complications © Cengage Learning 2016. All Rights Reserved. Hypoglycemia • Insulin excess causes brain-starving hypoglycemia – Low blood glucose • Glucagon in general opposes the actions of insulin – Actions on carbohydrate – Actions on fat – Actions on protein © Cengage Learning 2016. All Rights Reserved. Glucagon Secretion • Glucagon secretion is increased during the postabsorptive state – Decreases during the absorptive state • Insulin and glucagon work as a team to maintain blood glucose and fatty acid levels – Elevated blood glucose stimulates insulin secretion, but inhibits glucagon secretion © Cengage Learning 2016. All Rights Reserved. Glucose Homeostasis • Glucagon excess can aggravate the hyperglycemia of diabetes mellitus – Diabetics frequently have a high rate of glucagon secretion concurrent with insulin insufficiency • Epinephrine, cortisol, and growth hormone also exert direct metabolic effects – Refer to Table 19-5 • The hypothalamus plays a role in controlling glucose homeostasis © Cengage Learning 2016. All Rights Reserved. © Cengage Learning 2016. All Rights Reserved. 19.5 Parathyroid Glands and Control of Calcium Metabolism • Plasma Ca2+ must be closely regulated to prevent changes in neuromuscular excitability – Vital role in a number of essential activities • Control of Ca2+ metabolism includes regulation of both Ca2+ homeostasis and Ca2+ balance – Regulation of Ca2+ metabolism depends on hormonal control of exchanges between the ECF and the bone, kidneys, and intestine © Cengage Learning 2016. All Rights Reserved. Parathyroid Glands and Control of Calcium Metabolism • Parathyroid hormone raises free plasma Ca2+, a life-saving effect – Peptide hormone secreted by the parathyroid glands – Essential for life • Bone continuously undergoes remodeling – Bone remodeling: bone deposition (formation) and bone resorption (removal) © Cengage Learning 2016. All Rights Reserved. PTH and Ca2+ • Mechanical stress favors bone deposition – Causes bone mass to increase and bones to strengthen • PTH raises plasma Ca2+ – Withdraws Ca2+ from the bone bank • PTH’s immediate effect is to promote transfer of Ca2+ from bone fluid into plasma – See Figure 19-24 © Cengage Learning 2016. All Rights Reserved. Central canal Osteocyte Lamellae Lamella Canaliculi (c) Lamellae within an osteon Location of yellow marrow Compact bone Trabecular bone Osteon Central canal Trabecular bone (a) Long bone Compact bone Blood vessel from marrow Canaliculi Periosteum Lamella Central canal Osteocyte Vessel in central canal (b) Osteon Osteon © Cengage Learning 2016. All Rights Reserved. Source: Modified and redrawn with permission from Human Anatomy and Physiology, 3rd Edition, by A. Spence a Copyright © 1987 by The Benjamin/Cummings Publishing Company. Reprinted by permission of Pearson Educat photo: Biophoto Associates/Science Source Osteocytic– osteoblastic bone membrane Osteocyte Osteoblast Osteoblast Osteoclast Blood vessel Mineralized bone Outer surface Central canal Bone fluid Canaliculi Lamellae Gap junction KEY = Membrane-bound Ca2+ pump (a) Osteocytic–osteoblastic bone membrane In canaliculi Mineralized bone: stable pool of Ca2+ In central canal Bone fluid: labile pool of Ca2+ Plasma 1 Fast exchange Ca2+ 2 Slow exchange (Bone dissolution) Ca2+ Osteocytic–osteoblastic bone membrane (formed by filmy cytoplasmic extensions of interconnected osteocytes and osteoblasts) (b) Fast and slow exchange of Ca2+ between bone and plasma © Cengage Learning 2016. All Rights Reserved. 1 In a fast exchange, Ca2+ is moved from the labile pool in the bone fluid into the plasma by PTH-activated Ca2+ pumps located in the osteocytic–osteoblastic bone membrane. 2 In a slow exchange, Ca2+ is moved from the stable pool in the mineralized bone into the plasma through PTH- induced dissolution of the bone by osteoclasts. Effects of PTH • PTH’s chronic effect is to promote localized dissolution of bone in order to release Ca2+ into plasma – Acts on osteoblasts • Causes them to secrete RANKL • PTH acts on the kidneys – Conserves Ca2+ and eliminates PO43- © Cengage Learning 2016. All Rights Reserved. Effects of PTH (cont’d.) • PTH indirectly promotes absorption of Ca2+ and PO43- by the intestine – Helps activate vitamin D • The primary regulator of PTH secretion is plasma concentration of free Ca2+ – All effects of PTH raise plasma Ca2+ levels • Calcitonin lowers plasma Ca2+ concentration – Not important in normal Ca2+ metabolism © Cengage Learning 2016. All Rights Reserved. Ca2+ Metabolism • Vitamin D is actually a hormone that increases Ca2+ absorption in the intestine – Activation of vitamin D – Function of vitamin D • Phosphate metabolism is controlled by the same mechanisms that regulate Ca2+ metabolism – See Figure 19-27 © Cengage Learning 2016. All Rights Reserved. Relieves Plasma PO43− (Because of inverse relationship 3− 2+ between plasma PO4 and Ca 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 Ca2+ absorption in intestine Urinary excretion of Ca2+ (Counteract each other) Urinary excretion of PO43− No change in plasma Plasma PO43− © Cengage Learning 2016. All Rights Reserved. Ca2+ PO43− absorption in intestine Disorders in Ca2+ Metabolism • Disorders in Ca2+ metabolism may arise from abnormal levels of PTH or vitamin D – PTH hypersecretion: excess PTH secretion – PTH hyposecretion: deficient PTH secretion (i.e., hypoparathyroidism) – Vitamin D deficiency: major consequence is impaired intestinal absorption of Ca2 • May lead to rickets or osteomalacia © Cengage Learning 2016. All Rights Reserved. Points to Ponder • What do you think causes osteoporosis? Is it an estrogen deficiency? • The hypothalamic-pituitary axis may be activated under stress. How does this process occur? • What is the purpose of measuring fasting blood glucose levels? © Cengage Learning 2016. All Rights Reserved.