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Endocrine System Chapter 16 Overview • Overall goal of endocrine system: maintain a stable internal environment (homeostasis) • Endocrine glands are “ductless glands” • Endocrine glands secrete hormones which travel through the blood to a target cell – Receptor must be present on target cell • Glands of the endocrine system are present throughout the body • Most cells are regulated by the endocrine system Endocrine vs Nervous System • Both systems function to maintain homeostasis • Main differences: Feature Endocrine System Nervous System Effector cells Target cells throughout the body Postsynaptic cells in muscle and glandular tissue only Chemical messenger Hormone Neurotransmitter Distance traveled by messenger Long – in blood Short – across synaptic cleft Regulatory effects Slow to appear; long-lasting Appear rapidly; short Endocrine vs Nervous System Major Endocrine Glands Classification of Hormones • Classified by Function – Tropic hormones: target other endocrine glands and stimulate their growth & secretion – Sex hormones: target reproductive tissues – Anabolic hormones: stimulate anabolism in their target cell Classification of Hormones • Classified by Chemical Structure – Steroid Hormones • Derived from cholesterol • Lipid soluble; can pass through phospholipid bilayer – Nonsteriod Hormones • Synthesized from amino acids • Proteins, Glycoproteins, peptides, amino acid derivatives (Fig 16-3) Chemical Classifications of Hormones How Hormones Work • Hormones bind to receptors on target cells – Lock & key • Hormone-receptor interactions produce regulatory changes within the target cell – Ex: initiating protein synthesis; activation/inactivation of enzymes; opening/closing of ion channels • Endocrine glands produce more hormone molecules than necessary to hit the target cells – Excess hormones are excreted in urine or broken down by metabolic processes How Hormones Work • Synergism: combinations of hormones have a greater effect on the target cell compared to a single hormone acting alone • Permissiveness: a small amount of one hormone allows a second hormone to exhibit its full effect on the target cell • Antagonism: two hormones produce opposite effects Mechanisms of Steroid Hormone Action • Steroids are lipids not soluble in blood plasma (mostly H2O) • In blood steroids attach to plasma proteins • Steroid reaches a target cell dissociates from plasma protein diffuses into target cell • In the nucleus a hormone-receptor complex is formed • Hormone-receptor complexes in the nucleus trigger protein synthesis (transcription & translation) • Increase steroid = increase response (protein synthesis) • Regulatory effects of hormones are slow to appear Mechanisms of Steroid Hormone Action Mechanisms of Nonsteriod Hormone Action • Nonsteroid hormones operate according to the second messenger hypothesis – Nonsteroid hormone is the “1st messenger” and binds to a receptor on the plasma membrane of the target cell – The “message” is relayed inside the cell to a “2nd messenger” which triggers the appropriate cellular response Second Messenger Mechanism 1. 2. 3. Nonsteroid hormone (1st messenger) binds with receptor on plasma membrane Hormone-receptor complex activates a membrane protein called the G protein G protein activates guanosine triphosphate (GTP) which also activates another membrane protein (adenyl cyclase) Second Messenger Mechanism 4. 5. 6. Adenyl cyclase removes 2 phosphate groups from ATP creating cyclic adenosine monophosphate (cAMP) (second mesenger) cAMP activates or inactivates protein kinases Protein kinases activate specific intracellular enzymes Second Messenger Mechanism 7. Enzymes influence specific cellular reactions (target cell’s response to hormone) Second Messenger Mechanism Summary: • Hormone or 1st messenger binds to plasma membrane receptor • Triggers formation of intracellular 2nd messenger • 2nd messenger activates cascade of chemical reactions • Target cell’s response to the hormone is produced Another Second Messenger • Some hormones produce effects in target cells by triggering opening of calcium channels – – – – – – Hormone binds to receptor on plasma membrane Ca2+ channels open Ca2+ binds with calmodulin Ca2+/Calmodulin complex acts as 2nd messenger Enzymes are activated/inactivated Target cell’s response is produced Calcium-Calmodulin as 2nd Messenger Regulation of Hormone Secretion • Hormone secretion is controlled by a negative feedback loop – Ex: parathyroid hormone (PTH) and blood calcium levels (fig 16-10) – Ex: insulin and blood glucose levels Endocrine Feedback Loop Hyper vs Hyposecretion • Tumors or abnormalities of the endocrine glands cause secretion of too much or too little hormone • Hypersecretion: production of too much hormone • Hyposecretion: production of too little hormone – Results in lack of target cell response – Also caused by target cell insensitivity Regulation of Target Cell Sensitivity • Sensitivity of target cell depends on number of receptors it has for a specific hormone • Receptors are constantly begin broken down and re-synthesized by the cell • Up-regulation: synthesis of new receptors > degeneration of old receptors – Increase target cell sensitivity to that particular hormone • Down-regulation: synthesis of new receptors < degeneration of old receptors – Decrease target cell sensitivity Pituitary Gland • Also called hypophysis • Located on ventral surface of brain, inferior to the hypothalamus • “Master gland” because functions are crucial to life • Composed of two parts: Anterior Pituitary and Posterior Pituitary Anterior Pituitary • Hormones secreted from Anterior Pituitary: – Growth Hormone – Prolactin – Trophic hormones • Thyroid-stimulating hormone (TSH) • Adrenocorticotropic hormone (ACTH) • Gonadotropic hormones – Follicle-stimulating hormone (FSH) – Luteinizing hormone (LH) Growth Hormone • Growth Hormone (GH) – promotes growth by stimulating protein anabolism • Increased protein anabolism allows increased growth rate • Target cells: – Promotes growth of bone and muscle • GH has a hyperglycemic effect; antagonist of insulin – Hyperglycemic effect because GH stimulates fat metabolism – Interaction vital to maintaining homeostasis of blood glucose levels Growth Hormone Abnormalities • Hypersecretion – Prior to ossification of the epiphyseal plates hypersections of GH results in rapid skeletal growth Gigantism – After closure of epiphyseal plates hypersecretion causes cartilage to continue to form new bone Acromegaly • Distorted appearance; enlarged hands, feet, face, jaw; thickened skin Growth Hormone Abnormalities • Hyposecretion – Results in stunted body growth pituitary dwarfism – Treated with genetically engineered growth hormone Prolactin (PRL) • • • • Also called lactogenic hormone Initiates milk secretion (lactation) Target cells: Mammary glands During pregnancy PRL promotes development of breasts • At birth PRL stimulates milk production Prolactin Abnormalities • Hypersecretion: – Lactation in non-nursing women – Disruption of menstrual cycle – Impotence in men • Hyposecretion: – Insignificant unless mother wishes to breastfeed Trophic Hormones • Review: a trophic hormone stimulate effects of other endocrine glands • Trophic hormones released from anterior pituitary gland: – Thyroid-stimulating hormone (TSH) – Adrenocorticotropic hormone (ACTH) – Gonadotrophic hormones • Follicle-stimulating hormone (FSH) • Luteinizing hormone (LH) Thyroid-stimulating hormone (TSH) • Promotes and maintains growth and development of thyroid gland • Required for thyroid gland to secrete its hormones Adrenocorticotropic hormone (ACTH) • Promotes and maintains normal growth and development of the cortex (outer portion) of the adrenal gland • Required for adrenal cortex to secrete its hormone Gonadotrophic hormones • Target cells: gonads (testes & ovaries) • Follicle-stimulating hormone (FSH) – Females: • Stimulates growth & development of an ovum that is released each month during ovulation • Stimulate estrogen release from the ovaries – Males • Stimulates development of seminiferous tubules and maintains sperm production in the testes Gonadotrophic hormones • Luteinizing hormone (LH) – Females: • Triggers ovulation • Promotes development of corpus luteum which secretes progesterone and estrogen; these hormones help maintain pregnancy – Males: • Stimulates cells of the testes to synthesize and secrete testosterone Control of Anterior Pituitary Secretion • The hypothalamus releases chemical called releasing hormones which influence hormone secretion from the anterior pituitary gland • This regulatory mechanism is a negative feedback loop Posterior Pituitary • Hormones secreted from Posterior Pituitary: – Antidiuretic Hormone (ADH) – Oxytocin (OH) Antidiuretic Hormone (ADH) • Target cells: kidney • Prevents formation of large volumes of dilute urine • Antidiuresis • Helps conserve water balance • Example: – Blood is hypertonic change detected by osmoreceptors ADH is released water reabsorbed in kidneys and returned to blood ADH Abnormalities • Hyposecretion – – – – Diabetes insipidus Increased urine output of dilute urine “high and dry” Na+ levels are increased; ICF dehydrated • Hypersecretion – Syndrome of inappropriate antidiuretic hormone (SIADH) – Decreased urine output – Fluid overload; low Na+ levels Oxytocin (OT) • Target cells: mammary glands & uterine smooth muscle • Operates on a positive feedback loop • Stimulates uterine smooth muscle contractions – During childbirth stretching of receptors causes continued release of oxytocin until after delivery of the placenta • Ejection of milk into ducts of the breast of lactating women – When breastfeeding the suckling action of the baby causes secretion of additional oxytocin increasing milk production – Breastfeeding also helps the uterus continue to contract back to normal size during the postpartum period Project Reminders • Make sure your illustrations shows both the anterior and posterior pituitary. • Show ovaries and testes (only testes) • Remember that trophic hormones will be a double pathway • Plan ahead – we have not learned about all of the hormones yet so make sure you leave room for future information • You will be adding additional organs to represent target cells • Questions?? Pineal Body • Regulates the body’s biological clock – Patterns of eating – Sleeping – Female reproductive cycle – Behavior • Secretes melatonin – Induces sleep – Secretion is inhibited by sunlight – Target cell in humans is unknown Melatonin & Seasonal Affective Disorder • Also know as “winter depression” • During shorter days, melatonin secretion increases causes a depressed feeling in affected patients • Treatment – Exposure to high-intensity lights to inhibit melatonin secretion Thyroid Gland • The thyroid gland is composed of two lateral lobes connected by an isthmus • Located on the anterior and lateral surfaces of the trachea, below the larynx Thyroid Hormones • Tetraiodothyronine or thyroxine (T4) – Most abundant thyroid hormone – Contains 4 iodine atoms – May have effect on target cells, but mostly serve as precursor to T3 • Triodothyronine (T3) – “principal thyroid hormone” – Contains 3 iodine atoms Thyroid Hormones • Both hormone bind to plasma proteins once secreted into the bloodstream • Function: – Regulate metabolic rate of all cells – Regulate cell growth – Regulate tissue differentiation • Target cells: “general” because thyroid hormones can potentially interact with all cells of the body Hypersection • Graves Disease – Autoimmune condition (thyroid stimulating antibodies causes abnormal secretion) – Weight loss – Increases basal metabolic rate – Increased heart and respiratory rate – exophthalmos Exophthalmos Hyposecretion of Thyroid Hormone • Cretinism – develops during the growth years due to hypothyroidism – Low metabolic rate – Retarded growth and sexual development – Mental retardation (possibly) • Hypothyroidism later in life – – – – – – Decreased metabolic rate Loss of mental & physical vigor Weight gain Loss of hair Yellow discoloration of the skin myxedema Goiter • Caused by lack of iodine in the diet • Iodine is needed to synthesize thyroid hormone • Lack of iodine causes drop in thyroid hormone production/secretion • Negative feedback loop informs hypothalamus and anterior pituitary to release releasing hormones and TSH • Lack of iodine causes enlargement of thyroid gland Calcitonin • The 3rd hormone secreted from the thyroid gland • Target cells – bone • Function – regulates calcium levels in the blood by decreasing blood calcium levels – Increases action of osteoblasts (build bone) and inhibits action of osteoclasts (breakdown bone) – Antagonist to parathyroid hormone Parathyroid Glands • Parathyroid glands are embedded in the posterior aspect of the thyroid glands • Usually 4 or 5 parathyroid glands Parathyroid Hormone • Secreted from Parathyroid glands • Target cells: bone and kidney • Action: maintains calcium homeostasis – Increases osteoclast activity; decrease osteoblast activity – Calcium absorbed in kidneys and returned to the bloodstream – Activates vitamin D in the kidneys which increases intestinal absorption of calcium • Parathyroid hormone is an antagonist to calcitonin Adrenal Glands • Located on top of both of the kidneys • Composed of two parts: – Outer portion adrenal cortex – Inner portion adrenal medulla • Both parts of the adrenal glands are structurally and functionally different; often treated as two different glands Adrenal Cortex • Composed of three distinct layers or zones – Outer zone secrete mineralocorticoids – Middle zone secrete glucocorticoids – Inner zone secrete glucocorticoids and gonadocorticoids Mineralocorticoids • Mineralocorticoids – regulate electrolytes in the body • In humans the most important mineralcorticoid is aldosterone • Target cell – kidneys • Function – maintaining sodium homeostasis in the blood – In the kidneys, sodium ions are reabsorbed from the urine back to the blood – Sodium ions are exchanged for potassium or hydrogen ions – Aldoesterone also promotes water retention because reabsorption of sodium ions also causes water to be reabsorbed Regulation of Aldosterone Secretion • • Aldosterone secretion is controlled by the reninangiotensin mechanism This mechanism is a negative feedback loop that helps maintain homeostasis of blood pressure 1. Blood pressure drops in the kidneys renin (an enzyme) is secreted 2. Renin converts angiotensinogen to angiotensin I 3. Angiotensin I travels to the lungs where enzymes split the molecule forming angiotensin II 4. Angiotensin II travels to the kidneys where it simulates the secretion of aldosterone 5. Aldosterone causes reabsorption of sodium ions followed by water reabsorption increase in blood pressure Glucocorticoids • Main glucocorticoid secreted from the adrenal cortex is cortisol (also hydrocortisone) • Target cells – general; affect every cell in the body Cortisol - Functions • Accelerate protein breakdown into amino acids – Amino acids travel to liver and are converted to glucose (gluconeogenesis) – Increased glucocorticoids (cortisol) increased breakdown of proteins in tissue (tissue wasting) hyperglycemia • Shift cells from carbohydrate catabolism to lipid catabolism for energy sources – Further causes hyperglycemia Cortisol – Functions cont… • Help maintain blood pressure – Permissiveness relationship with epinephrine and norepinephrine – Epi and NE cause vasoconstriction of blood vessels • Suppression of immune system responses Glucocorticoid Hypersecretion • Cushing Syndrome – Too much cortisol is being secreted – Causes: • Could be caused by hypersecretion of ACTH from anterior pituitary (tumor) • Cirrhosis of liver or liver failure can’t breakdown hormones – Signs/Symptoms: • • • • • • • Abnormal hair growth buffalo hump muscle wasting skin breakdown (thin skin) striae across abdomen and thighs truncal obesity Susceptible to infection Adrenal Insufficiency • Hyposecretion of mineralcorticoids & glucocorticoids Addison Disease • Signs/Symptoms: – Drop in blood sodium – Hypoglycemia – Increase in blood potassium – Dehydration – Weight loss Adrenal Medulla • Secretes two nonsteroids in the catecholamine class – Epinephrine and norepinephrine – Bind to sympathetic effectors and enhance the effects of the “fight or flight” response of the autonomic nervous system Pancreas • Located in the LUQ • Contains both endocrine and exocrine tissue • Endocrine portion is made up of tiny islands of cells called pancreatic islets (also islets of Langerhans) • Alpha cells secrete glucagon • Beta cells secrete insulin Pancreatic Hormones • Glucagon – Increases blood glucose levels • Converts glycogen to glucose in liver cells • Stimulates gluconeogenesis – Target cells liver • Insulin – Decreases blood glucose levels • Promotes movement of glucose, amino acids, fatty acids into cells • Promotes metabolism of these molecules once by cells – Target cells general (all cells) • Glucagon and Insulin produce antagonistic effects (fig 16-27, page 512) Diabetes • Results from either – 1) inadequate or absence of insulin production – 2) Insulin resistance – decreased insulin receptors results in decreased effectiveness of glucose uptake Diabetes – Signs & Symptoms • Hyperglycemia – elevated amounts of glucose in the blood – Results glucose not entering the cells properly • Glycosuria – glucose present in the urine – Elevated glucose levels in the blood exceeds kidney’s abilities to reabsorb glucose; glucose “spills over” into the urine • Polyuria – increased urine production – Water follows glucose lost in urine Diabetes – Signs & Symptoms • Polydipsia – excessive thirst – Polyuria causes dehydration • Polyphagia – excessive and continuous hunger – Although blood sugar is high cells are “starving” because cells cannot uptake glucose **3 P’s = polyuria, polydipsia, polyphagia** Diabetic Ketoacidosis • Diabetics are unable to utilize glucose for energy – cells must use protein and fat • Large quantities of fat metabolism results in build up of acidic metabolites called ketone bodies • Signs/Symptoms – – – – – – – Acidosis Abdominal pain Nausea/vomiting Fruity breath Decreased LOC Coma death Type 1 Diabetes • Absolute deficiency of insulin production • Cause of beta cell destruction is unknown • Requires insulin injections or an insulin pump Type 2 Diabetes • Previously called non-insulin-dependent diabetes (NIDDM) or adult onset diabetes • Beta cell produce reduced amounts of insulin • Loss of insulin receptors on target cells leads to insulin resistance • Treated with insulin injections, oral diabetic medication and lifestyle modifications Complications of Diabetes Untreated or poorly controlled diabetes can lead to many complications that affect almost every system in the body: • Atherosclerosis – build up of fatty materials in the blood vessls – Lead to heart attack, stroke, reduced circulation • Diabetic retinopathy – can lead to blindless Complications of Diabetes • Neuropathy – nerve damage – Amputations • Kidney disease – May require dialysis Gonads – Testes & Ovaries Testes: • Composed mainly of coils of seminiferous tubules & interstitial cells • Interstitial cells secrete testosterone • Target cells – general • Function: – Growth & maintenance of male sexual characteristics – Sperm production • Testosterone secretion is regulated by the gonadotropin leutinizing hormone (LH) Gonads – Testes & Ovaries Ovaries: • Estrogen – Secreted by cells of the ovarian follicles – Target cells: general – Functions: • Promote development & maintenance of female sexual characteristics • Breast development • Regulation of menstrual cycle Gonads – Testes & Ovaries Ovaries: • Progesterone (“pregnancy-promoting hormone”) – Secreted by corpus luteum – Target cells: general – Functions (with estrogen): • Maintains the lining of the uterus to maintain a pregnancy • Remember Estrogen & Progresterone secretion is regulated by FSH and LH (gonadotropic hormones) Placenta • Tissue that forms along the lining of the uterus • Serves as the connection between the circulatory systems of the mother and developing fetus • Secretes human chorionic gonadotropin (hCG) • Target cells: ovaries Placenta • Function: – Stimulates hormone (estrogen & progesterone) secretion from the ovaries – High levels of estrogen & progesterone help maintain uterine lining for pregnancy • hCG is high during the 1st trimester • A high hCG level is used to confirm a pregnancy