Endocrine System Notes PDF

The Endocrine System Extrinsic Regulation of Homeostasis Intro through Pituitary Gland Homeostasis A state of chemical and thermal balance Maintenance of a stable internal environment Nervous and endocrine systems responsible for the maintenance of homeostasis Endocrine system respo...

The Endocrine System Extrinsic Regulation of Homeostasis Intro through Pituitary Gland Homeostasis A state of chemical and thermal balance Maintenance of a stable internal environment Nervous and endocrine systems responsible for the maintenance of homeostasis Endocrine system responsible for long- term processes like growth, development and reproduction Nervous system takes care of the split- second responses Both systems working together to maintain homeostasis - neuroendocrine response Nervous System Versus Endocrine System: Differences Nervous System Endocrine System Neurons release neurotransmitters Sends commands via hormones that close to target cells are released directly into the Signal travels along axons like a signal bloodstream and ECF (extracellular through a telephone wire fluid) Effects occur quickly but are short- Affects specific target cells that lived contain receptors for the hormone Effects often restricted to specific Response is slow target cells Effects last a long time and are more Excellent for crisis management widespread Figure 17.2 Quick Review of Intercellular Communication Endocrine communication via hormones Affects all body systems Hormones released directly into the bloodstream and ECF to affect the activities of specific cells (target cells) Target cells have the specific receptors needed to bind the hormone and read/interpret its message Hormones change the type, amount and activity of important enzymes and proteins Endocrine System detects and responds to internal and external changes in the environment Changes in the environment represent a stress/stimulus to which the endocrine system will respond Bozeman Science Cell Communication Copyright © 2018, 2015, 2012 Pearson Education, Inc. 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All R ights R eserved  Classes of Hormones Amino Acid Derivatives Derived from the amino acids tyrosine and tryptophan Amino Acids are the building blocks for proteins Tyrosine derivatives include thyroid hormone and the catecholamines epinephrine, norepinephrine and dopamine Primary tryptophan derivative is melatonin Peptide Hormones Chains of amino acids Most are synthesized as prohormones (inactive state) Can be activated before or after secretion Glycoproteins – have CH2O chains – TSH, LH, FSH Small Polypeptides/Small Proteins – GH, PRL, ADH, OT, hormones released from the heart, thymus, digestive tract and pancreas  Classes of Hormones 2 Lipid Derivatives Eicosanoids – signaling molecules that include leukotrienes, prostaglandins, thromboxanes and prostacyclins Steroid Hormones are lipids that are structurally similar to cholesterol that differ according to the side chain on the ring structure Over time these steroids are absorbed by the liver and converted to a soluble form that can be excreted in urine or bile (feces) Examples: Androgens, estrogens, progestins, corticosteroids, calcitriol Remain in circulation longer than other hormones because they are transported bound to a transport protein  What Hormones Do? Mechanisms of Action 1. Coordinate cell, tissue and organ activities 2. Alter membrane permeability 3. Activate or inactivate enzymes 4. Change genetic activity (via protein synthesis) Hormones must interact with the appropriate receptor to affect the target cell Receptors are proteins to which hormones bind The number and types of receptors a cell has determines its sensitivity to a hormone Receptors are found on the outside surface of the plasma membrane or inside the cell Lipid soluble molecules diffuse across the plasma membrane to reach receptors on the inside of the cell (steroid hormones and eicosanoids) – Direct Effect Catecholamines and peptide hormones bind to receptors on the outside of the cell – Indirect Effect (second messenger needed) Indirect Effect of Hormones Hormone binds to receptor on the surface of the cell Example: Epinephrine binds to a Beta receptor Binding of the hormone causes activation of a G protein which is bound to the cytoplasmic side of the plasma membrane G protein acts as an intermediary between the 1st messenger (the hormone) and the 2nd messenger Activated G protein activates other enzymes Example: adenylate cyclase which catalyzes the conversion of ATP to cAMP cAMP acts as a 2nd messenger (usually by activating a protein kinase) Kinases are enzymes that catalyze the phosphorylation (addition of a phosphate) of other molecules Effects of this cascade of events depends on the nature of the phosphorylated proteins Can open ion channels or activate other enzymes First messenger examples in this cascade = epinephrine and norepinephrine when attached to β receptors, CT, ADH, PTH, ACTH, FSH, LH, TSH https://www.youtube.com/watch?v=ejq99wLEMTw Video: https://www.youtube.com/watch?v=ejq99wLEMTw Indirect Effect of Hormones (PDE) Hormone binds to a receptor on the surface of the cell Example: Epinephrine binds to an Alpha 2 receptor G protein is activated Activated G protein stimulates the activity of Phosphodiesterase (PDE) Activation of PDE inhibits adenylate cyclase Inhibition of adenylate cyclase inhibits production of cAMP Decreases in cAMP cause an inhibition of the phosphorylation of cellular enzymes Cellular enzymes remain inactive Occurs when epinephrine and norepinephrine bind to ἁ2 receptor Indirect Effect of Hormones (PLC) Hormone binds to the surface receptor Example: Epinephrine binds to an Alpha 1 receptor G protein is activated Activated G protein activates Phospholipase C (PLC) leading to the production of Diaceylglycerol (DAG) and Inositol Triphosphate (IP3) IP3 diffuses into the cytoplasm and triggers the release of Ca2+ from the SER Oxytocin on uterine smooth muscles DAG and Ca2+ activate protein kinase C (PKC) Activation of PKC may lead to phosphorylation of calcium channel proteins which allow calcium to flow into the cell Calcium acts as a 2nd messenger Calcium binds to calmodulin forming an enzyme complex The enzyme complex activates cytoplasmic enzymes Occurs with the binding of epinephrine to an alpha-1 receptor and the binding of OT, several hypothalamic hormones and some eicosanoids Direct Effect of Hormones (Steroids) Steroid hormones diffuse through the cell membrane Steroid hormones bind to receptors in the cytoplasm and nucleus Hormone-receptor complexes bind to DNA and activate or deactivate specific genes Transcription of DNA is altered Protein synthesis is altered Metabolic activity and structure of the target cell is altered Direct Effect of Hormones (TH) Thyroid hormone crosses the plasma membrane and binds to receptors in the nucleus or on the mitochondria Hormone-receptor complexes activate certain genes or change the rate of transcription Metabolic activity is altered by the increased or decreased concentrations of specific enzymes TH bound to a mitochondrial membrane causes an increase in the production of ATP  Modulation of target cell sensitivity Target cells can adjust their sensitivity to a hormone by changing the number or receptors Up-regulation: a cell increases the number of receptors and becomes more sensitive Pregnancy of OT receptors of uterine muscles Down-regulation: cell reduces its receptor population Aging Disease or genetics Over exposure to high hormone concentration Adipocytes down regulate when exposed to high levels of insulin Testis down regulate when LH levels are too high Control of Hormones: Negative Feedback Negative Feedback – most common means of restoring homeostasis Results in stable amounts of hormone needed to perform cellular metabolic activities Endocrine glands are sensitive to changes in hormone concentrations Decreased concentrations – hormone production Increased concentrations – inhibition of hormone production  Negative Feedback Loop Example Hypothalamus: Anterior Pituitary Gland: Secretion of TRH Secretion of TSH (thyroid releasing hormone) (thyroid stimulating hormone) Thyroid Gland Follicular Cells Secretion of T3 and T4 Decreased T3 and T4 levels Decreased cellular metabolism Decreased body temp. All bodily cells Increase cellular metabolism Increase body temperature Homeostasis  Control of Hormones: Positive Feedback Positive Feedback Unstable mechanism with extreme responses Found in times of potentially dangerous or stressful situations to restore homeostasis Examples – ? bleeding, labor and delivery and breast feeding Severe cut – blood loss – decreased B/P and cardiac efficiency Damaged bld. vessels release chemicals that promote movement of platelets to the damaged tissue/vessel Arrival of platelets causes an increased release of chemicals that promote movement of platelets to the damaged tissue/vessel Arrival of platelets causes an increased release of chemicals that promote movement of platelets … When the hole in the vessel is plugged up, there is a decreased release of chemicals that cause the movement of platelets to the site of the damages tissue/vessel Decrease in the chemical release leads to a decrease in movement of platelets which leads to a further decrease in chemical release until homeostasis is restored  Positive Feedback Loop Example Hypothalamus: Signals posterior pituitary Posterior Pituitary Gland: to release Oxytocin (OT) Secretion of OT Oxytocin targets smooth muscle of uterine lining Fetal head applies pressure on cervix Contraction of smooth muscles within uterus Positive Feedback and Blood Clotting Copyright © 2018, 2015, 2012 Pearson Education, Inc. 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All R ights R eserved  Hypothalamic-Pituitary Axis Hypothalamus controls pituitary Stimulation through infundibulum Integrates the activities of the nervous and endocrine systems by Secreting regulatory hormones Releasing and Inhibiting Hormones (RH and IH) Acts as an endocrine organ (produces OT & ADH) Exerts direct neural control over adrenal medulla Endocrine reflexes occur in response to Changes in ECF composition Arrival/removal of a hormone Arrival of neurotransmitter  Hypophyseal Portal System Several capillary networks unite to form a series of vessels that lead to the anterior pituitary Blood goes from one capillary to the next instead from an artery to a capillary to a venous structure Unusual arrangement allows hypothalamic hormones to get to target cells of the pituitary without becoming diluted in the general circulation Communication is one way – from hypothalamus to pituitary Hypothalamic Releasing and Inhibiting Hormones Releasing hormones (RH)stimulate the release of hormones by the anterior pituitary Inhibiting hormones (IH)prevent the synthesis and secretion of the hormones of the anterior pituitary RH and IH are secreted in response to the concentrations of the different hormones via a negative feedback PIH = prolactin inhibiting mechanism hormone aka dopamine PRF = prolactin releasing factor PRL = prolactin  Negative Feedback Loop Example Hypothalamus: Anterior Pituitary Gland: Secretion of TRH Secretion of TSH (thyroid releasing hormone) (thyroid stimulating hormone) Thyroid Gland Follicular Cells Secretion of T3 and T4 Decreased T3 and T4 levels Decreased cellular metabolism Decreased body temp. All bodily cells Increase cellular metabolism Increase body temperature Homeostasis  Pituitary Gland AKA master gland and hypophysis Controls all other glands 3 Lobes 1. Anterior lobe aka adenohypophysis and pars distalis Anterior lobe made of many endocrine cells that produce and release hormones 2. Posterior pituitary aka pars nervosa and neurohypophysis Posterior lobe made of nervous tissue – stores and releases hormones that are produced in the hypothalamus (OT & ADH) Does NOT synthesize any hormones!! 3. Pars intermedia – anterior pituitary found between the pars distalis and the pars nervosa Pituitary Histology  Anterior Pituitary Composed of 2 Groups of cells divided into 5 types of cells TYPES = TROPIC cells (tropic = stimulate/turn on) Group 1 - Basophils – cytoplasm stains purplish Thyrotropes Thyroid stimulating hormone (TSH) Controls secretion of T3 and T4 = Regulates metabolism Gonadotropes Luteinizing hormone (LH) aka Interstitial Cell Stimulating hormone (ICSH) in males Promotes secretion of sex hormones in males, and egg release from ovary in females TYPES Follicle stimulating hormone (FSH) Growth and development of ovarian follicle and production and secretion of estrogen Corticotropes Adrenocorticotropic releasing hormone (ACTH) from hypothalamic stimulation Stimulates adrenal cortex to secrete aldosterone, cortisol, and androgens  Anterior Pituitary Composed of 2 Groups of cells divided into 5 types of cells Group 2 - Acidophils– cytoplasm stains pinkish Somatotropes Growth Hormone (GH) Stimulates growth and repair of cells Mammotropes Prolactin (PRL) TYPES Stimulates production of milk in females and decreases the production of LH in males (too much LH in males can lead to possible infertility) Give The Cashier Some Money  Tropic Hormones of the Anterior Pituitary Tropic – to turn on Thyrotropin aka TSH (Thyroid Stimulating Hormone) Released by thyrotropes of the anterior pituitary in response to TRH (thyroptropin releasing hormone) Stimulates the follicular cells of the thyroid to produce and release thyroid hormones T3 and T4 Corticotropin aka ACTH (adrenocorticotropic hormone) Released by corticotropes of the anterior pituitary in response to CRH (corticotropin releasing hormone) Stimulates the zona fasciculata of the adrenal cortex to produce and secrete glucocorticoids (cortisol) Gonadotropins are released by gonadotropes of the anterior pituitary in response to GnRH (gonadotropin releasing hormone) Follitropin aka FSH (follicle stimulating hormone) Stimulates follicular maturation in the ovaries and, in combination with LH, production of estrogens in females  Negative Feedback Loop Example Hypothalamus: Anterior Pituitary Gland: Secretion of TRH Secretion of TSH (thyroid releasing hormone) (thyroid stimulating hormone) Thyroid Gland Follicular Cells Secretion of T3 and T4 Decreased T3 and T4 levels Decreased cellular metabolism Decreased body temp. All bodily cells Increase cellular metabolism Increase body temperature Homeostasis  Follitropin In Males Promotes the production and maturation of sperm by nurse cells of the testes Production of follitropin is inhibited by Inhibin, a hormone produced in the testes and ovaries Lutropin aka LH (Luteinizing Hormone) Secreted by the gonadotropes of the anterior pituitary Induces ovulation and secretion of estrogen and progesterone in females Promotes the production of androgens in the male LH is also called ICSH (interstitial cell stimulating hormone) in males Mammotropin aka PRL (prolactin) Released by mammotropes of the anterior pituitary in response to PRF (prolactin releasing factor) **Stimulates the development of the mammary glands and milk production in females **Makes interstitial cells of the testes more sensitive to ICSH Mammotropin production inhibited by PIH (dopamine)  Somatotropin aka GH (Growth Hormone) Released by somatotropes of the anterior pituitary in response to GHRH Stimulates cell growth and replication Direct Effects of GH In fat – GH stimulates the breakdown of triglycerides (lipolysis) leading to an increase fatty acid concentration in the blood Considered glucose sparing because it slows down the breakdown of glucose in the tissues In the liver – GH stimulates the breakdown of glycogen reserves (glycogenolysis) Considered to be diabetogenic because it increases the concentration of glucose in the blood Indirect Effects of GH Liver cells produce and release somatomedins or IGF’s (insulin-like growth factors) IGF’s allow cells to easily produce ATP via aerobic metabolism of glucose IGF’s make amino acids readily available for protein synthesis Abnormalities in production of GH include dwarfism, gigantism, and acromegaly **Normal growth requires the presence of GH, TH, insulin, PTH, calcitriol and reproductive hormones (We will discuss these as we move through the endocrine system)  Pars Intermedia aka Pars Intermedius Part of the anterior pituitary Between the pars distalis and pars nervosa Produces melanotropin aka MSH (melanocyte stimulating hormone) Causes increased production of melanin by melanocytes Pars intermedia non-functional in adults Melanotropin produced locally by sun-exposed skin in adults Melanotropin secreted during fetal development, during early childhood, sometimes during pregnancy and in some disease (reasons for the last 2 are not clearly understood)  Posterior Pituitary Also known as the neurohypophysis or pars nervosa Contains axons of hypothalamic neurons Hormones move along the axons in the infundibulum to axon terminals that end in basal capillaries in the posterior pituitary No hormones synthesized Two hormones stored and released Antidiuretic hormone (ADH) Oxytocin (OT)  Antidiuretic Hormone (ADH) Vasopressin aka ADH (Antidiuretic Hormone) Released in response to increases in solute concentration of the blood a fall in blood volume or fall in B/P Osmoreceptors in the hypothalamus detect changes in solute concentrations and ADH is released or suppressed accordingly Primary Function of ADH – decrease water loss Secondary Function of ADH - vasoconstriction In high concentrations ADH causes rise in B/P Release inhibited by alcohol (explains alcohol’s diuretic effect) Diabetes insipidus (Lack of ADH production)  Oxytocin (OT) Oxy = quick; Tokos = childbirth Stimulates smooth muscle contraction of the uterus and mammary ducts Uterine muscles are insensitive to OT until late in pregnancy Beginning of labor and delivery due to a sudden rise in OT OT also released from the uterus and fetus Responsible for the “let down” of milk after childbirth OT secretion and milk ejection is an example of a neuroendocrine reflex Infant sucks – sensory nerves in the nipple signal the hypothalamus – OT is released – milk released (positive feedback mechanism) OT release during stress, baby crying, intercourse OT in males causes smooth muscle contraction in the vas deferens and prostate gland causing the ejection of sperm, secretions from the prostate and other glands in the male reproductive tract before ejaculation Pituitary Histology Hypothalamic and Pituitary Control. Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Pages 616-617 Endocrine System Thyroid through Adrenal Gland  Thyroid Gland Found anterior to the trachea Has 2 lobes connected by the isthmus Thyroid Gland Composed of thyroid follicles Follicular cells surround thyroglobulin (a thick colloid substance with many dissolved proteins, iodine and molecules of T3 and T4 Extrafollicular cells surround the follicular cells and are responsible for the secretion of calcitonin Follicular cells production of thyroid hormones (T3 and T4) via a complex chemical pathway *TH is used for increased cellular metabolism via receptors on mitochondria and within nucleus Release of TH is controlled by TSH from the anterior pituitary Most T3 and T4 are bound to TBGs (thyroid-binding globulins) TBGs hold will release or bind the thyroid hormones as we need them to maintain homeostasis  Thyroid Histology Follicular cells (1) and Colloid (2) Parathyroid Gland 2 1 Thyroid Gland  As bound TH is released into the blood stream and taken up by the tissues, a disequilibrium occurs in the concentration of TH in the blood To maintain equilibrium, more bound TH is released until blood concentrations are restored Active transport of I- molecules is stimulated by TSH I- goes into the follicle to be used for the synthesis of TH We get I- in our diet – if no iodine in the diet, stores are depleted and TH can not be synthesized Decreases in TSH or absence of TSH leads the thyroid follicles to become inactive High levels of TSH coupled with low levels of T3 and T4 may indicate thyroid issues such as hypothyroidism Hyperthyroidism may be due to many factors Autoimmune (Grave’s disease) Plummer’s disease (cancerous nodules)  Decrease Body Temp/Cellular metabolism Hypothalamus: Anterior Pituitary Gland: Secretion of TRH Thyrotropes (thyroid releasing hormone) Secretion of TSH (thyroid stimulating hormone) Thyroid Gland Follicular Cells Secretion of T3 and T4 Decreased T3 and T4 levels Decreased cellular metabolism Decreased body temp. All bodily cells Increase cellular metabolism Increase body temperature Homeostasis  C Cells and Calcitonin C for clear (aka parafollicular/extrafollicular cells) Produce and release CT (calcitonin) CT decreases the levels of Ca2+ in the blood Inhibits osteoclasts – slows Ca2+ release from the bone Help stimulate osteoblast activity Stimulates excretion of calcium by the kidneys Inhibit Ca2+ absorption at small intestine C cells respond directly to increases of calcium in the blood Calcitonin is needed for bone growth and mineral deposition in children  Increased Blood Calcium Thyroid Bone Extrafollicular cells Inhibition of Osteoclasts Secretion of CT Increases calcium deposition in (Calcitonin) bone Kidneys Increases calcium excretion Increased blood Small intestines calcium levels Decrease intestinal absorption of calcium Homeostasis Decrease blood calcium levels Parathyroid Glands 2 pair embedded in the posterior thyroid – separated from the thyroid by a dense capsule Chief cells produce PTH – increases blood Ca2+ Decreases in blood calcium levels stimulate chief cells Increases in calcium occur via Stimulation of osteoclasts (increased mineral turnover and release of calcium from the bone) Increased reabsorption of calcium by the kidneys Formation and release of calcitriol (enhances the actions of PTH, increases Ca2+ and PO43- absorption in the digestive tract) Oxyphil cells – no known function  Parathyroid Gland Histology and Loop  Decreased Blood Calcium Levels Parathyroid Bone Chief Cells Stimulation of Osteoclasts Secretion of PTH Osteolysis (breakup bone (Parathyroid Hormone) calcium and release into bloodstream) Kidneys Decrease calcium excretion Release of Calcitriol Decreased blood calcium levels Small intestines Increase intestinal absorption of calcium Homeostasis Decrease blood calcium levels Adrenal Glands Aka suprarenal glands – sit on top of the kidneys Capsule, Cortex, and medulla Adrenal Cortex - yellow because it stores lipids Adrenocortical steroids – corticosteroids Bound to transport proteins in the blood (transcortins) Life not possible without adrenal cortical hormones unless replacement corticosteroids administered Adrenal Gland Histology Figure The Adrenal Gland and Adrenal Hormones. CAPSULE G F R ATLAS: Plates 61a,b; 62b Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved  Adrenal Cortex 3 regions – zona glomerulosa, zona fasciculata, zona reticularis Zona glomerulosa – mineralocorticoids produced and secreted here, mostly aldosterone Needed for F&E balance especially Na+ retention and K+ elimination Na+ retention leads to H2O conservation via the kidneys, sweat glands, salivary glands and pancreas Works best with adequate ADH production Aldosterone increases sensitivity of salt receptors of taste buds which increases the desire for and consumption of salty foods Aldosterone is secreted in response to: decreased blood volume decreased blood Na+ increased K+ increased angiotensin II  Zona Fasciculata Produces and secretes glucocorticoids – primarily cortisol (hydrocortisone) as well as corticosterone Liver converts cortisol to cortisone Secretion of glucocorticoids controlled by negative feedback Glucocorticoids: Increase rates of glucose and glycogen formation especially in the liver Cause release of fatty acids by adipose tissue (glucose sparing) so fatty acids and proteins breakdown instead of glucose Have an anti-inflammatory effect which decreases the activities of WBCs (slows migration of WBCs and decreases the number and activity of phagocytes) Makes basophils less likely to secrete histamine Impair would healing Glucose and Glycogen  Zona Reticularis Produces small amounts of androgens DHEA Dehydroepiandrosterone Androgens stimulate the development of secondary sex characteristics **Some androgens are converted to estrogens, DHT, or testosterone in the bloodstream Overproduction of androgens in a female lead to masculinization of the female leading to increased muscle mass, growth of facial hair, deepening of the voice Figure 18-14b The Adrenal Gland and Adrenal Hormones. CAPSULE G F R ATLAS: Plates 61a,b; 62b Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved  Adrenal Medulla Effects of Epinephrine and Secretory activities controlled by Norepinephrine: the sympathetic portion of the 1. Mobilize glycogen reserves in muscle ANS and increase the rate of glucose Produces epinephrine (E) and metabolism to release ATP for energy norepinephrine (NE) in vesicles Muscle strength and endurance are increased within the cell 2. In adipose – stored fats are broken down E and NE continuously released in into fatty acids and fatty acids are used small quantities via exocytosis in ATP production Stimulation of the sympathetic 3. In liver – glycogen broken down which portion of the ANS causes an increases blood glucose increased rate of exocytosis and Glucose needed for neural tissue function hormone release 4. In heart – stimulates beta and alpha 1 Effects of E and NE peaks at about receptors which increases HR and force 30 seconds and lasts a few minutes of cardiac contractions thereafter  Adrenal Disorders Cushing syndrome—excess cortisol secretion Causes: ACTH hypersecretion by pituitary, ACTH-secreting tumors, hyperactivity of adrenal cortex Hyperglycemia, hypertension, weakness, edema Rapid muscle and bone loss due to protein catabolism Abnormal fat deposition; moon face and buffalo hump Adrenogenital syndrome (A GS)—adrenal androgen hypersecretion (often accompanies Cushing) Enlargement of external sexual organs in children and early onset of puberty; newborn girls exhibit masculinized genitalia Masculinizing effects on women; increased body hair, deeper voice, beard growth Addison’s Disease Adrenal insufficiency  CAPSULE G F R MEDULLA  Class and 1 hormone Class and hormone 2 Class 3 and hormone 4 Hormones ATLAS: Plates 61a,b; 62b Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Endocrine System Pancreas through Kidney Pancreas Gross Anatomy ATLAS: Plate 49e Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved  Pancreas Has both exocrine and endocrine functions Exocrine – 99% - pancreatic acini attached to ducts Secretes alkaline, enzyme rich fluids that travel in the pancreatic duct to the small intestine Endocrine – Islets of Langerhans (about 2 million) Alpha (20%), Beta (70%), Delta (5%) and F cells (~5%) Pancreas Alpha cells produce glucagon In liver, stimulates gluconeogenesis (use of amino acids to produce “new” glucose), glycogenolysis, and the release of glucose into the circulation raising blood glucose level In adipose tissue, stimulates fat catabolism and release of free fatty acids Glucagon also released in response to rising amino acid levels in blood, promotes amino acid absorption, and provides cells with raw material for gluconeogenesis  GLP-1 Glucagon-like peptide 1 Secreted from pancreatic alpha cells L-cells of small intestine…primary secretion location Hypothalamus Secreted in response to nutrient load Typically following a meal (postprandial) Regulates glucose levels Stimulates release of insulin and reduces glucagon secretion “helps lower A1C” Controls appetite by promoting satiety Acts on the vagus nerve Injections of GLP-1 agonist inhibit hunger Slows intestinal motility Reduces gastric emptying and motility Reduces postprandial glycemic levels  Pancreas Beta cells Produce Insulin (decreases blood glucose) and Amylin Normal Blood sugar – 70 to 99 mg/dL Insulin Increases rate of glucose uptake by the cells and stimulates an increase in transport proteins to move glucose into the cells Increases glucose utilization and ATP production Increases glycogen formation by the liver and muscles Stimulates AA absorption and protein synthesis Stimulates triglyceride formation in adipose and the rate of glucose absorption in adipose tissue Amylin Reduces glucose spikes – co-secreted with insulin slows stomach emptying, modulates gastric secretions, inhibits glucagon secretion, and signals satiety (feeling full)  Pancreas Delta cells produce somatostatin (GHIH) Only about 5% of islet cells Inhibits the release of glucagon and insulin Slows rates of food absorption and enzyme secretion F cells produce PP (pancreatic polypeptide) Decreases gallbladder contractions Regulates production of pancreatic enzymes – reduces secretions of enzymes that are no longer needed May control rate of nutrient absorption ATLAS: Plate 49e Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Pancreas Histology Islet of Langerhans Islet of Langerhans  Liver and muscles specifically ______________ 70-99mg/dL Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved ______________ 70-99mg/dL Gluconeogenesis (formation of new glucose from non- carbohydrate source) Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved  Pancreas Hyperglycemia Abnormally high glucose levels in the blood Normal fasting glucose = 70-99 mg/dL HbA1C = percent of glucose bound to hemoglobin Measures blood glucose over lifespan of RBC (approx. 3 months) Normal = below 5.7% (over 6.5% indicates diabetes) Diabetes mellitus Characterized by high glucose concentrations that overwhelm reabsorption capabilities of kidneys Glucose appears in urine Polyuria Urine volume becomes excessive High risk of diabetic ketoacidosis Diabetes Type 1 Type 2 Characterized by inadequate Most common form insulin production by pancreatic Usually, normal amounts of beta cells insulin are produced, at least May be due to an autoimmune initially disorder Tissues do not respond Patients require daily injections properly (insulin resistance) or continuous infusion of insulin Associated with obesity Approximately 5 percent of Weight loss can be an cases effective treatment Usually develops in children and young adults Secondary Endocrine Functions ▪ Organs with secondary endocrine functions Intestines (digestive system) Kidneys (urinary system) Heart (cardiovascular system) Thymus (lymphatic system) Gonads (reproductive system) 86 Thymus Produces and releases thymosins Thymosins promote the development of T lymphocytes (T-Cells) T cells coordinate and regulate specific immune responses Term T cell comes from the fact that these cells are differentiated in the thymus  Pineal Gland Secretory cells are called pinealocytes Produces melatonin from serotonin Melatonin Inhibits reproductive function and plays a role in sexual maturation (onset of puberty) Levels of melatonin decrease at puberty Elimination of melatonin leads to premature puberty Protects against free radicals (antioxidant function) Free radical = unstable molecule that may cause cell damage Can effect the DNA Sets circadian rhythms – day and night patterns for physiologic processes Color blue is believed to inhibit melatonin creation….stimulates serotonin SAD Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Secondary Endocrine Functions Intestines Release hormones that coordinate digestive activities Kidneys Release the hormones calcitriol and erythropoietin (EPO) Release the enzyme renin Renin converts angiotensinogen to angiotensin I In the lungs, angiotensin-converting enzyme converts angiotensin I to angiotensin II Kidneys Renin – released in response to decreased renal blood flow Renin-Angiotensin Mechanism: Renin is secreted by the kidneys and converts Angiotensinogen (released from the liver) into Angiotensin I Angiotensin I is converted to Angiotensin II by ACE (released from the lungs) which stimulates the release of ADH and aldosterone Sodium and water are conserved, thirst and B/P increase EPO (erythropoietin) – stimulates bone marrow to produce RBC’s Released in response to increase in O2 demand, decrease in O2 saturation for any reason, decrease in circulating RBC’s  ACE inhibitor ACE (angiotensin converting enzyme) From lungs Hypothalamus/Post. Pituitary ADH production/release Water reabsorption at Kidneys Angiotensinogen Angiotensin I Angiotensin II (liver) Hypothalamus Osmoreceptors Stimulation of thirst Kidneys Red Bone Increase RBC Adrenal Cortex (Zona Glomerulosa) Renin Marrow production Aldosterone release Sodium reabsorption at Kidneys EPO Vasoconstriction of peripheral blood vessels Decreased renal B/P and oxygen Increase water Homeostasis Increase B/P intake and ECF Increase oxygenation fluid Copyright © 2018, 2015, 2012 Pearson Education, Inc. All R ights R eserved Kidneys Release Calcitriol in response to PTH to increase the level of calcium in the blood Works in conjunction with the parathyroid glands to maintain calcium homeostasis Vitamin D3 (cholecalciferol) synthesized in the skin or absorbed from the diet Converted to calcitriol Stimulates absorption of Ca2+ and PO4-3 in the digestive tract Stimulates formation of osteoprogenitor cells and osteoblasts Stimulates bone resorption by osteoblasts Stimulates Ca2+ reabsorption by the kidneys Suppresses PTH production Calcium Absorption X Endocrine System Heart to Hormonal Interactions Last Set of Notes  Heart (out of order) ANP and BNP Blood volume increases – stretch receptors detect the increase – natriuretic peptides released Natriuretic = Salty Urine Natriuretic peptides promote loss of sodium and water Natriuretic peptides inhibit release of renin, ADH & aldosterone – decreases B/P, blood volume & thirst ANP and BNP are antagonists to Angiotensin II  Inhibit Baroreceptors Heart (atrial stretch receptors) (hypothalamus) Release ANP Posterior pituitary decreases ADH secretion Decrease water reabsorption at the kidneys Adrenal Cortex (Zona Glomerulosa) Decrease Aldosterone secretion Increase Blood volume/BP Decrease sodium reabsorption at the kidneys Stretching of atrial walls Kidneys Decrease Renin release Vasodilation Homeostasis Decrease fluid intake and reabsorption/Increase fluid output (excretion) Decrease blood volume Decrease blood volume/BP  Adipose Tissue Leptin – feedback control of appetite… (stimulated by insulin) Needed for normal levels of GnRH and gonadotropin synthesis Gives a sense of satiation Discovered when researchers were working with obese mice High fructose corn syrup interferes with the release of leptin preventing a feeling of satiation ***Ghrelin (not an adipose hormone): released from gastric cells in response to empty stomach. Signals sensation of hunger (antagonistic to Leptin) Resistin – reduces insulin sensitivity Believed to be the correlation between obesity and type II diabetes Adiponectin – increases tissue sensitivity to insulin…(stimulated by insulin) Increases transport and utilization of glucose and free fatty acids Decreases gluconeogenesis Antagonist to Resistin Release inhibited by GH, testosterone, glucocorticoids, and prolactin …..levels of adiponectin decline in obese individuals Secondary Endocrine Functions (Gonads) Ovaries and Testes….to be discussed in Reproductive notes  Hormonal Interactions Antagonists – have opposite effects (i.e. CT and PTH) Synergists – have additive effects (i.e. glucose sparing of GH and glucocorticoids) Permissive Effects – 1st hormone needed for the second to exert its effect (i.e. effects of epinephrine depend on the presence of TH) Integrative Effects – 2 hormones produced in different parts of the body that have different but complementary effects (i.e. calcitriol and PTH) Found in complex physiological systems like the endocrine system Additive Effects of Synergist (blood glucose)  GAS: General Adaptation Syndrome Hormonal Response to Stress Anything that alters homeostasis is a stress General (less specific) responses to stress 3 phases of GAS Alarm, Resistance, Exhaustion Let’s paint a scene….. GAS: General Adaptation Syndrome Hormonal Response to Stress Alarm Phase – immediate response Epinephrine is the dominant hormone Energy stores are mobilized Glucose and fat are used for immediate energy Body gets ready to deal with stress (fight or flight) Directed by the sympathetic portion of the ANS  Alarm Phase of GAS Characterized by Increased mental alertness Increased energy consumption by tissues Mobilization of energy reserves Increased blood flow to skeletal muscles Decreased blood flow to skin, kidneys and digestive organs Drastic reduction in digestion and urine production Increased sweat gland secretion Increased B/P, HR, RR  Resistance Phase of GAS Resistance Phase – If stress lasts longer than a few hours Seen in starvation, acute illness, severe anxiety Can last hours, days, weeks Glucocorticoids are the dominant hormones Epinephrine, TH, Aldosterone, and GH also involved Energy demands increase Lipids reserves can be used for weeks or even months during this phase (fatty acid metabolism…..may lead to increase in ketones in blood = acidosis)  Resistance Phase of GAS Characterized by Mobilization of remaining energy reserves (lipids and AAs) Conservation of glucose to be used by neural tissues with lipid breakdown for energy Increased blood glucose via liver synthesis from CHO, lipids and AAs Conservation of sodium and water and loss of potassium (K+) and hydrogen ions (H+) As you enter acidosis, you must remove the hydrogens Increase H+ = acidic  Exhaustion Phase of GAS Homeostatic regulation no longer possible without intervention Lipid reserves are exhausted Inability to produce glucocorticoids Can no longer balance electrolytes Unless corrective actions are taken organ failure is imminent  Primary vs Secondary Disorders Primary disorder Problem with the gland/organ itself Tumors, trauma, dietary insufficiencies … Secondary disorder Problem with other organs that affect the target organ Examples – problems with the hypothalamus and pituitary cause global endocrine problems Crash course Review Videos https://www.youtube.com/ watch?v=eWHH9je2zG4 https://www.youtube.com/ watch?v=SCV_m91mN-Q