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Endocrine System: Overview Endocrine system – the body’s second great controlling system which influences metabolic The Endocrine System activities of cells by means of hormones Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus Part A The pancreas and gonads produce both hormones and exocrine products Endocrine System: Overview Major Endocrine Organs The hypothalamus has both neural functions and releases hormones Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart Figure 16.1 Intercellular communication Intercellular communication Autocrine Direct communication chemicals that exert effects on the same Through gap junctions cells that secrete them Ions, small solutes, etc Paracrine Limited to adjacent cells of the same type locally acting chemicals that affect cells other than those that secrete them Synaptic communication Cytokines or local hormones Neurotransmitters These are not considered hormones since Used in crises management hormones are long-distance chemical signals 1 Intercellular communication Types of Hormones Endocrine Amino acid based Hormones – chemical substances secreted Amines, thyroxine, peptide, and protein by cells into the extracellular fluids hormones Regulate the metabolic function of other cells Peptides hormones Have lag times ranging from seconds to Short peptides hours ADH, oxytocin Tend to have prolonged effects Small proteins GH, prolactin Types of Hormones Hormone Action Hormones that bind to receptors in the cell Lipid derivatives membrane: Steroids – gonadal and adrenocortical First and second messengers hormones Regulatory G proteins Eicosanoids – leukotrienes and prostaglandins Water-soluble hormones Function as paracrine and autocrine Hormones that bind to intracellular receptors factors Direct gene activation Function as hormones Steroid and thyroid hormones The precise response depends on the type of the target cell Hormones that bind to receptors in the cell Mechanism of Hormone Action membrane: cAMP mechanism Hormones produce one or more of the Hormone (first messenger) binds to its receptor, which then binds to a G protein following cellular changes in target cells The G protein is then activated as it binds Alter plasma membrane permeability GTP, displacing GDP Stimulate protein synthesis Activated G protein activates the effector Activate or deactivate enzyme systems enzyme adenylate cyclase Induce secretory activity Adenylate cyclase generates cAMP (second Stimulate mitosis messenger) from ATP cAMP activates protein kinases, which then cause cellular effects 2 Hormones that bind to receptors in the cell Hormones that bind to receptors in the cell membrane : cAMP mechanism membrane: PIP-Calcium mechanism Extracellular fluid Hormone A Adenylate cyclase Hormone B 1 1 Hormone binds to the receptor and activates G protein Receptor Gs 2 GTP 3 GTP 4 GTP 3 GTP 2 Gi Receptor G protein binds and activates phospholipase GTP GDP GDP GTP Catecholamines ATP cAMP Phospholipase splits the phospholipid PIP2 into ACTH 5 FSH LH Triggers responses of target cell (activates enzymes, diacylglycerol (DAG) and IP3 (both act as Glucagon stimulates cellular PTH TSH Inactive Active secretion, opens ion channels, etc.) second messengers) Calcitonin protein protein kinase A kinase A DAG activates protein kinases; IP3 triggers Cytoplasm release of Ca2+ stores Ca2+ (third messenger) alters cellular responses Hormones that bind to receptors in the cell membrane: PIP-Calcium mechanism Hormones that bind to intracellular Extracellular fluid receptors Hormone 1 DAG Steroid Hormones This interaction prompts DNA transcription 2 GTP 3 GTP PIP2 4 5 Active protein to produce mRNA Receptor Gq kinase C Inactive GTP GDP IP3 protein kinase C The mRNA is translated into proteins, which Catecholamines Phospholipase C TRH ADH 5 Triggers responses of target cell bring about a cellular effect GnRH Oxytocin Endoplasmic 6 reticulum Cytoplasm Ca2+ Ca2+- calmodulin Steroid hormone Cytoplasm Steroid Target Cell Specificity hormone Receptor- chaperonin complex Hormones circulate to all tissues but only Receptor-hormone complex Molecular activate cells referred to as target cells chaperones Binding Hormone Target cells must have specific receptors to response elements which the hormone binds Transcription Chromatin These receptors may be intracellular or mRNA mRNA located on the plasma membrane Nucleus Ribosome New protein Translation 3 Target Cell Specificity Target Cell Activation Target cell activation depends on three factors Examples of hormone activity Blood levels of the hormone ACTH receptors are only found on certain Relative number of receptors on the target cells of the adrenal cortex cell Thyroxin receptors are found on nearly all The affinity of those receptors for the cells of the body hormone Target Cell Activation Hormone Concentrations in the Blood Up-regulation – target cells form more Hormones circulate in the blood in two forms: receptors in response to the hormone free or bound Down-regulation – target cells lose receptors Steroids and thyroid hormone are attached in response to the hormone to plasma proteins Bound to their own carriers Hormone Concentrations in the Blood Interaction of Hormones at Target Cells Permissiveness – one hormone cannot exert Concentrations of circulating hormone reflect: its effects without another hormone being Rate of release present. Estrogen and thyroid hormone Speed of inactivation and removal from the Synergism – more than one hormone body produces the same effects on a target cell Hormones are removed from the blood by: Glucagon and epinephrine Degrading enzymes Antagonism – one or more hormones opposes the action of another hormone. The kidneys Glucagon and insulin Liver enzyme systems 4 Control of Hormone Release Humoral Stimuli Blood levels of hormones: Humoral stimuli – secretion of hormones in Are controlled by negative feedback systems direct response to changing blood levels of Vary only within a narrow desirable range ions and nutrients Hormones are synthesized and released in Example: concentration of calcium ions in the response to: blood Humoral stimuli Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete Neural stimuli PTH (parathyroid hormone) Hormonal stimuli PTH causes Ca2+ concentrations to rise and the stimulus is removed Humoral Neural Stimuli Stimuli Neural stimuli – nerve fibers stimulate hormone release Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines Hormonal Hormonal Stimuli Stimuli Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs The hypothalamic hormones stimulate the anterior pituitary In turn, pituitary hormones stimulate targets to secrete still more hormones 5 Nervous System Modulation Nervous System Modulation The nervous system can override normal The nervous system modifies the stimulation endocrine controls of endocrine glands and their negative For example, control of blood glucose levels feedback mechanisms Normally the endocrine system maintains blood glucose Under stress, the body needs more glucose The hypothalamus and the sympathetic nervous system are activated to supply ample glucose Major Endocrine Organs: Pituitary Pituitary (Hypophysis) (Hypophysis) Pituitary gland – two-lobed organ that secretes nine major hormones Neurohypophysis – posterior lobe (neural tissue) and the infundibulum Receives, stores, and releases hormones from the hypothalamus Adenohypophysis – anterior lobe, made up of glandular tissue Synthesizes and secretes a number of hormones Pituitary-Hypothalamic Relationships: Pituitary-Hypothalamic Relationships: Posterior Lobe Anterior Lobe The posterior lobe is a downgrowth of hypothalamic neural tissue The anterior lobe of the pituitary is an Has a neural connection with the outpocketing of the oral mucosa hypothalamus (hypothalamic-hypophyseal There is no direct neural contact with the tract) hypothalamus Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH) These hormones are transported to the posterior pituitary 6 Pituitary-Hypothalamic Relationships: Pituitary-Hypothalamic Relationships: Anterior Lobe Anterior Lobe There is a vascular connection, the hypophyseal portal system, consisting of: The primary capillary plexus The hypophyseal portal veins The secondary capillary plexus Adenophypophyseal Hormones Activity of the Adenophypophysis The six hormones of the adenohypophysis: The hypothalamus sends a chemical stimulus Abbreviated as GH, TSH, ACTH, FSH, LH, to the anterior pituitary and PRL Releasing hormones stimulate the synthesis Regulate the activity of other endocrine and release of hormones glands Inhibiting hormones shut off the synthesis In addition, pro-opiomelanocortin (POMC): and release of hormones Has been isolated from the pituitary Is split into ACTH, opiates, and MSH Thyroid Stimulating Hormone Activity of the Adenophypophysis (Thyrotropin) The tropic hormones that are released are: Stimulates the normal development and Thyroid-stimulating hormone (TSH) secretory activity of the thyroid Adrenocorticotropic hormone (ACTH) Triggered by hypothalamic peptide Follicle-stimulating hormone (FSH) thyrotropin-releasing hormone (TRH) Luteinizing hormone (LH) Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH 7 Adrenocorticotropic Hormone Gonadotropins (Corticotropin) Gonadotropins – follicle-stimulating hormone Stimulates the adrenal cortex to release (FSH) and luteinizing hormone (LH) corticosteroids Regulate the function of the ovaries and Triggered by hypothalamic corticotropin- testes releasing hormone (CRH) in a daily rhythm FSH stimulates gamete (egg or sperm) Internal and external factors such as fever, production hypoglycemia, and stressors can trigger the Absent from the blood in prepubertal boys and girls release of CRH Triggered by the hypothalamic gonadotropin-releasing hormone (GnRH) during and after puberty Functions of Gonadotropins Functions of Gonadotropins In females In males LH works with FSH to cause maturation of LH stimulates interstitial cells of the testes to the ovarian follicle produce testosterone LH works alone to trigger ovulation LH is also referred to as interstitial cell- (expulsion of the egg from the follicle) stimulating hormone (ICSH) LH promotes synthesis and release of estrogens and progesterone Growth Hormone (GH) Growth Hormone (GH) Produced by somatotropic cells of the Antagonistic hypothalamic hormones regulate anterior lobe that: GH Stimulate most cells, but target bone and Growth hormone–releasing hormone skeletal muscle (GHRH) stimulates GH release Promote protein synthesis and encourage Growth hormone–inhibiting hormone (GHIH) the use of fats for fuel inhibits GH release Most effects are mediated indirectly by somatomedins 8 Metabolic Action of Growth Hormone Metabolic Action of Growth Hormone (GH) GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors Direct action promotes lipolysis and inhibits glucose uptake The Posterior Pituitary and Prolactin (PRL) Hypothalamic Hormones Posterior pituitary – made of axons of In females, stimulates milk production by the hypothalamic neurons, stores antidiuretic breasts hormone (ADH) and oxytocin Triggered by the hypothalamic prolactin- ADH and oxytocin are synthesized in the releasing hormone (PRH) hypothalamus Inhibited by prolactin-inhibiting hormone ADH influences water balance (PIH) Oxytocin stimulates smooth muscle Blood levels rise toward the end of pregnancy contraction in breasts and uterus Both use PIP-calcium second-messenger Suckling stimulates PRH release and mechanism encourages continued milk production Oxytocin Oxytocin is a strong stimulant of uterine contraction The Endocrine System Regulated by a positive feedback mechanism to oxytocin in the blood This leads to increased intensity of uterine PART B contractions, ending in birth Oxytocin triggers milk ejection (“letdown” reflex) in women producing milk 9 Oxytocin Antidiuretic Hormone (ADH) ADH helps to avoid dehydration or water Synthetic and natural oxytocic drugs are used overload to induce or hasten labor Prevents urine formation Plays a role in sexual arousal and satisfaction Osmoreceptors monitor the solute in males and nonlactating females concentration of the blood With high solutes, ADH preserves water With low solutes, ADH is not released, thus causing water loss Alcohol inhibits ADH release and causes copious urine output Thyroid Gland Thyroid Gland The largest endocrine gland, located in the anterior neck, consists of two lateral lobes connected by a median tissue mass called the isthmus Composed of follicles that produce the glycoprotein thyroglobulin Colloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid hormone Other endocrine cells, the parafollicular cells, produce the hormone calcitonin Thyroid Hormone Effects of Thyroid Hormone TH is concerned with: Thyroid hormone – major metabolic hormone Glucose oxidation Consists of two related iodine-containing Increasing metabolic rate compounds Heat production T4 – thyroxine; has two tyrosine molecules TH plays a role in: plus four bound iodine atoms Maintaining blood pressure T3 – triiodothyronine; has two tyrosines with Regulating tissue growth three bound iodine atoms Developing skeletal and nervous systems Maturation and reproductive capabilities 10 Synthesis of Thyroid Hormone Synthesis of Thyroid Hormone Thyroglobulin is synthesized and discharged into the lumen Iodinated tyrosines link together to form T3 Iodides (I–) are actively taken into the cell, and T4 oxidized to iodine (I2), and released into the Colloid is then endocytosed and combined lumen with a lysosome, where T3 and T4 are Iodine attaches to tyrosine, mediated by cleaved and diffuse into the bloodstream peroxidase enzymes, forming T1 (monoiodotyrosine, or MIT), and T2 (diiodotyrosine, or DIT) Thyroid follicle cell Capillary 1 Thyroglobulin is synthesized and discharged into the follicle lumen Colloid Transport and Regulation of TH Golgi Colloid in lumen of follicle apparatus 3b Iodine is attached T4 and T3 bind to thyroxine-binding globulins (TBGs) Rough ER to tyrosine in colloid, forming DIT and MIT produced by the liver Iodine Both bind to target receptors, but T3 is ten times Iodide 2 Iodide (I–) is trapped 3a Iodide is oxidized Thyroglobulin colloid more active than T4 (I–) (actively transported in) to iodine DIT (T2) MIT (T1) T4 Peripheral tissues convert T4 to T3 T3 T4 4 Iodinated tyrosines are Lysosome T3 T4 T3 linked together to form T3 and T4 Mechanisms of activity are similar to steroids Regulation is by negative feedback T3 5 Thyroglobulin colloid T4 is endocytosed and Hypothalamic thyrotropin-releasing hormone (TRH) 6 Lysosomal enzymes cleave combined with a T4 and T3 from thyroglobulin T4 T3 lysosome can overcome the negative feedback To peripheral colloid and hormones diffuse tissues from follicle cell into bloodstream Calcitonin Calcitonin A peptide hormone produced by the Calcitonin targets the skeleton, where it: parafollicular, or C, cells Inhibits osteoclast activity (and thus bone Lowers blood calcium levels in children resorption) and release of calcium from the Antagonist to parathyroid hormone (PTH) bone matrix Stimulates calcium uptake and incorporation into the bone matrix Regulated by a humoral (calcium ion concentration in the blood) negative feedback mechanism 11 Parathyroid Glands Parathyroid Glands Tiny glands embedded in the posterior aspect of the thyroid Cells are arranged in cords containing oxyphil and chief cells Chief (principal) cells secrete PTH PTH (parathormone) regulates calcium balance in the blood Effects of Parathyroid Hormone Effects of Parathyroid Hormone PTH release increases Ca2+ in the blood as it: Stimulates osteoclasts to digest bone matrix Enhances the reabsorption of Ca2+ and the secretion of phosphate by the kidneys Increases absorption of Ca2+ by intestinal mucosal Rising Ca2+ in the blood inhibits PTH release Adrenal (Suprarenal) Glands Adrenal Cortex Synthesizes and releases steroid hormones Adrenal glands – paired, pyramid-shaped called corticosteroids organs atop the kidneys Different corticosteroids are produced in each of the three layers Structurally and functionally, they are two Zona glomerulosa – mineralocorticoids glands in one (chiefly aldosterone) Adrenal medulla – neural tissue that acts as Zona fasciculata – glucocorticoids part of the SNS (chiefly cortisol) Adrenal cortex – glandular tissue derived Zona reticularis – gonadocorticoids from embryonic mesoderm (chiefly androgens) 12 Adrenal Cortex Mineralocorticoids Regulate electrolytes in extracellular fluids Aldosterone – most important mineralocorticoid Maintains Na+ balance by reducing excretion of sodium from the body Stimulates reabsorption of Na+ and secretion of K+ by the kidneys Mineralocorticoids The Four Mechanisms of Aldosterone Secretion Aldosterone secretion is stimulated by: Renin-angiotensin mechanism – kidneys Rising blood levels of K+ release renin, which is converted into angiotensin II that in turn stimulates Low blood Na+ aldosterone release Decreasing blood volume or pressure Plasma concentration of sodium and potassium – directly influences the zona glomerulosa cells ACTH – causes small increases of aldosterone during stress Atrial natriuretic peptide (ANP) – inhibits activity of the zona glomerulosa Major Mechanisms of Aldosterone Secretion Glucocorticoids (Cortisol) Help the body resist stress by: Keeping blood sugar levels relatively constant Maintaining blood volume and preventing water shift into tissue Cortisol provokes: Gluconeogenesis (formation of glucose from noncarbohydrates) Rises in blood glucose, fatty acids, and amino acids 13 Excessive Levels of Glucocorticoids Gonadocorticoids (Sex Hormones) Excessive levels of glucocorticoids: Most gonadocorticoids secreted are Depress cartilage and bone formation androgens (male sex hormones), and the most important one is testosterone Inhibit inflammation Androgens contribute to: Depress the immune system The onset of puberty Promote changes in cardiovascular, neural, The appearance of secondary sex and gastrointestinal function characteristics Sex drive in females Androgens can be converted into estrogens after menopause Adrenal Medulla Adrenal Medulla Made up of chromaffin cells that secrete Epinephrine is the more potent stimulator of epinephrine and norepinephrine the heart and metabolic activities Secretion of these hormones causes: Norepinephrine is more influential on Blood glucose levels to rise peripheral vasoconstriction and blood Blood vessels to constrict pressure The heart to beat faster Blood to be diverted to the brain, heart, and skeletal muscle Stress and the Adrenal Gland Pancreas A triangular gland, which has both exocrine and endocrine cells, located behind the stomach Acinar cells produce an enzyme-rich juice used for digestion (exocrine product) Pancreatic islets (islets of Langerhans) produce hormones (endocrine products) The islets contain two major cell types: Alpha (α) cells that produce glucagon Beta (β) cells that produce insulin 14 Glucagon Pancreas A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent Its major target is the liver, where it promotes: Glycogenolysis – the breakdown of glycogen to glucose Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates Release of glucose to the blood from liver cells Insulin Effects of Insulin Binding A 51-amino-acid protein consisting of two amino acid chains linked by disulfide bonds The insulin receptor is a tyrosine kinase Synthesized as part of proinsulin and then enzyme excised by enzymes, releasing functional insulin After glucose enters a cell, insulin binding triggers enzymatic activity that: Insulin: Lowers blood glucose levels Catalyzes the oxidation of glucose for ATP production Enhances transport of glucose into body cells Polymerizes glucose to form glycogen Counters metabolic activity that would Converts glucose to fat (particularly in enhance blood glucose levels adipose tissue) Diabetes Mellitus (DM) Regulation of Blood Glucose Levels The hyperglycemic Results from hyposecretion or hypoactivity of effects of glucagon insulin and the The three cardinal signs of DM are: hypoglycemic Polyuria – huge urine output effects of insulin Polydipsia – excessive thirst Polyphagia – excessive hunger and food consumption Hyperinsulinism – excessive insulin secretion, resulting in hypoglycemia 15 Diabetes Mellitus (DM) Gonads: Female Paired ovaries in the abdominopelvic cavity produce estrogens and progesterone They are responsible for: Maturation of the reproductive organs Appearance of secondary sexual characteristics Breast development and cyclic changes in the uterine mucosa Gonads: Male Pineal Gland Testes located in an extra-abdominal sac Small gland hanging from the roof of the third (scrotum) produce testosterone ventricle of the brain Testosterone: Secretory product is melatonin Initiates maturation of male reproductive Melatonin is involved with: organs Day/night cycles Causes appearance of secondary sexual Physiological processes that show rhythmic characteristics and sex drive variations (body temperature, sleep, Is necessary for sperm production appetite) Maintains sex organs in their functional state Other Hormone-Producing Structures Thymus Lobulated gland located deep to the sternum Heart – produces atrial natriuretic peptide Major hormonal products are thymopoietins (ANP), which reduces blood pressure, blood and thymosins volume, and blood sodium concentration These hormones are essential for the Gastrointestinal tract – enteroendocrine cells development of the T lymphocytes (T cells) of release local-acting digestive hormones the immune system Placenta – releases hormones that influence the course of pregnancy 16 Other Hormone-Producing Structures Developmental Aspects Kidneys – secrete erythropoietin, which Hormone-producing glands arise from all signals the production of red blood cells three germ layers Skin – produces cholecalciferol, the precursor Endocrine glands derived from mesoderm of vitamin D produce steroid hormones Adipose tissue – releases leptin, which is Endocrine organs operate smoothly involved in the sensation of satiety, and throughout life stimulates increased energy expenditure Most endocrine glands show structural changes with age, but hormone production may or may not be affected Developmental Aspects Developmental Aspects Exposure to pesticides, industrial chemicals, Ovaries undergo significant changes with age arsenic, dioxin, and soil and water pollutants and become unresponsive to gonadotropins disrupts hormone function Female hormone production declines, the Sex hormones, thyroid hormone, and ability to bear children ends, and problems glucocorticoids are vulnerable to the effects associated with estrogen deficiency (e.g., of pollutants osteoporosis) begin to occur Interference with glucocorticoids may help Testosterone also diminishes with age, but explain high cancer rates in certain areas effect is not usually seen until very old age Developmental Aspects GH levels decline with age and this accounts for muscle atrophy with age Supplemental GH may spur muscle growth, reduce body fat, and help physique TH declines with age, causing lower basal metabolic rates PTH levels remain fairly constant with age, and lack of estrogen in women makes them more vulnerable to bone-demineralizing effects of PTH 17
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