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Chapter 18: The Endocrine System

COMPARISON OF CONTROL BY THE NERVOUS AND ENDOCRINE SYSTEM -the nervous and endocrine systems work together to coordinate body system functions and maintain homeostasis within the body -the nervous system acts through nerve impulses (action potentials) conducted along neuron axons. -at synapses, nerve impulses trigger the release of neurotransmitters (mediator/messenger molecules) -Endocrine system controls activities by releasing mediators called hormones Hormone-a mediator molecule that is released in one part of the body but regulates the activity of cells in another part of the body -most enter the interstitial fluid and then the bloodstream, and bloodstream delivers hormones to cells -both neurotransmitters and hormones work by binding to receptors on/in their target cells -several mediators act as both neurotransmitters and hormones (ex. Norepinephrine ) CHARACTERISTIC Mediator molecules

Site of mediator action

Types of target cells

Time to onset of action Duration of action

NERVOUS SYSTEM Neurotransmitters (released LOCALLY in response to nerve impulses) -close to the site of release (at synapse) -binds to receptors in postsynaptic membrane -muscle cells (smooth, cardiac, and skeletal) -gland cells -other neurons Fast (within milliseconds) Briefer (milliseconds)

ENDOCRINE SYSTEM Hormones (delivered to tissues in WHOLE BODY by blood) -far from site of release (usually-some local) -binds to receptors on or in target cells -cells throughout the whole body

Slow (seconds-hours-days) Longer (seconds to days)

ENDOCRINE GLANDS -The body has two kinds of glands: Exocrine and Endocrine Exocrine glands: -secrete products into ducts that carry the secretions into body cavities, into the lumen of an organ, or to the outer surface of the body -Include sudoriferous (sweat), sebaceous (oil), ceruminous, mucous and digestive glands

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Chapter 18: The Endocrine System Endocrine glands: -secrete products (hormones) into interstitial fluid and then into the bloodstream (blood capillaries) where it is delivered to target tissues -have a huge dependence on the cardiovascular system, therefore endocrine glands are highly vascularized Endocrine glands include: -pituitary gland (anterior and posterior) -thyroid -parathyroid -adrenal glands -pineal glands There are also several glands that are not endocrine glands but secrete hormones: -hypothalamus -thymus -pancreas -ovaries -testes -kidneys -stomach -liver -small intestine -skin -heart -adipose tissue -placenta The Endocrine System=all endocrine glands and hormone-secreting cells taken together

Functions of Hormones 1) Help regulate: a. Chemical composition and volume of interstitial fluid b. Metabolism and energy balance c. Contraction of smooth and cardiac muscle fibers d. Glandular secretions e. Some immune system activities 2) Growth control and development 3) Regulate operation of reproductive systems 4) Help establish circadian rhythm Hormones only affect the specific target. Hormones influence target cell by chemically binding to specific protein receptors on the plasma membrane of the target cell (water-soluble), or inside the target cell (lipid-soluble) 2

Chapter 18: The Endocrine System

Down-regulation = the number of target cell receptors may decrease if a hormone is present in excess Ex) High amount LH hormone in blood, then the number of LH-receptors decreases -down-regulation makes a target less sensitive to the hormone (cause less receptors so therefore less binding) Up-regulation= the number of receptors on a target cell may increase in response to a hormone deficiency -makes the target cell more sensitive to the hormone Circulating Hormones=the hormones pass from the secretory cells that make them, into interstitial fluid and then into the blood -may linger in the blood and exert their effects for a few mins to hours -are eventually inactivated by the liver and excreted by the kidneys Local Hormones=hormones that act locally on neighbouring cells or on the same cell that secreted them without entering the bloodstream -are usually inactivated quickly Autocrines=local hormones that act on the same cell that secreted them Paracrines=local hormones that act on neighbouring cells without entering the bloodstream

CHEMICAL CLASSES OF HORMONES 1) Lipid Soluble Hormones 2) Water Soluble Hormones

1) Lipid Soluble Hormones a. Steroid Hormones (derived from cholesterol) b. Thyroid Hormones (2) (T3 and T4) c. Nitric Oxide (NOg) Receptors are located inside the target cells and hormones have to go through the plasma membrane to get inside to the receptors 1) A free, lipid-soluble hormone molecule diffuses from blood to interstitial fluid through the lipid bilayer of plasma membrane into the target cell 2) Hormone binds to and activates receptors in cytosol or nucleus. The receptorhormone complex alters gene expression by turning specific genes in the DNA on or off 3) DNA is transcribed and new RNA forms, leaves nucleus, and enters cytosol where it directs the synthesis of a new protein 4) The newly synthesized protein changes the cells activity and cause the response that is expected for that hormone

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Chapter 18: The Endocrine System

2) Water Soluble Hormones a. Amine Hormones (include the catecholamines-epinephrine, norepinephrine, and dopamine) b. Peptide and Protein Hormones c. Eicosanoid Hormones-are important circulating and local hormones i. Prostaglandins-lipids released by damaged cells that are involved in the inflammatory response, modify responses to hormones, dilate airways, regulate body temperature, and influence formation of blood clots ii. Leukotrienes-participate in allergic and inflammatory responses -water soluble hormones bind to integral transmembrane proteins (the receptors) in the plasma membrane of the target cell First Messenger-a hormone that binds to the receptor at the outer surface of the plasma membrane Second Messenger-a hormone produced inside the target cell, triggered by the binding of the first messenger to the outside of the cell (First messenger triggers production of second messenger, and second messenger is what actually triggers the hormone-stimulated response) 1) Water soluble hormone (the first messenger) diffuse from blood through interstitial fluid and binds to receptor in plasma membrane of target cell. The hormonereceptor complex activates production of a membrane protein called the G protein. 2) G protein activates adenylate cyclase 3) Adenylate Cyclase converts ATP into cyclic AMP (cAMP) in the cytosol of the cell 4) cAMP (the second messenger) activates one or more protein kinases Protein kinase-an enzyme phosphorylates other proteins 5) Activated protein kinases phosphorylates some proteins. Phosphorylation turns some proteins on (activates), and turns some proteins off (inactivates) 6) Phosphorylated proteins cause reactions that produce the physiological response *phosphorylation can also inhibit certain proteins 7) An enzyme inactivates cAMP and cells response is turned off -hormones that bind to plasma membrane receptors can induce their effects at very low concentrations because they initiate a chain reaction, where each step multiplies the initial effect

Hormone Transport in the Blood -most water-soluble hormone molecules circulate in the watery blood plasma in “free form”-not attached to other molecules -most lipid-soluble hormone molecules are bound to transport proteins

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Chapter 18: The Endocrine System The transport proteins (made in the liver) have 3 functions 1) Make lipid-soluble proteins temporarily water soluble (increases blood solubility) 2) Inhibit passage of small molecule hormones via a kidney filtering mechanism, and thereby slowing the rate of hormone loss in the blood 3) Provide a ready reserve of hormone, already present in the bloodstream Free Fraction- 0.1-10% of the molecules of a lipid-soluble hormone are not bound to a transport protein. This Free Fraction diffuses out of capillaries, binds to receptors, and triggers responses -As free hormone molecules leave the blood and bind to their receptors, transport proteins release new ones to replenish the free fraction

Hormone Interactions The responsiveness of a target cell to a hormone depends on: -the hormones concentration in the blood -the abundance of a target cells hormone receptors -influences exerted by other hormones -the higher the concentration of hormones, or the higher the number of receptors, the more vigorously the target cell responds (more of the activity the hormone is expected to elicit) -the actions of some of the hormones on target cells require a simultaneous or recent exposure to a second hormone -the second hormone is said to have a permissive effect (the first hormone acts more strongly when combined with the second hormone-they need each other to reach their full potential) Synergistic Effect-when the effect of two hormones acting together is greater or more extensive than the effect of the hormone acting alone (the 2 hormones have a synergistic effect on each other) Antagonistic Effect-when one hormone opposes the actions of another hormone

CONTROL OF HORMONE SECRETION -the release of most hormones occurs in short bursts with little to no secretion between bursts -when stimulated, an endocrine gland will release its hormone in more frequent bursts -in the absence of a stimulus the blood level of that hormone decreases -Secretion regulation helps prevent overproduction or underproduction to help maintain homeostasis Hormone secretion is regulated by: 1) Signals from the nervous system 2) Chemical changes in the blood 3) Other hormones -most hormone regulatory systems are negative feedback systems, some are positive feedback systems

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Chapter 18: The Endocrine System

HYPOTHALAMUS AND PITUITARY GLAND Pituitary gland-secretes several hormones that control other endocrine glands The Hypothalamus controls the pituitary gland The hypothalamus (located below the thalamus) is the major link between the nervous and endocrine systems Infundibulum-a stalk that attached the pituitary gland to the hypothalamus The pituitary gland has two separate portions-anterior and posterior pituitary, as well as a third portion called the pars intermedia 1)Anterior Pituitary -composed of epithelial tissue -secretes hormones -human growth hormone (hGH) -Thyroid stimulating hormone (TSH) -Follicle stimulating hormone (FSH) -Luteinizing hormone (LH) -Prolactin (PL) -Adrenocorticotropic hormone (ACTH) -Melanocyte stimulating hormone (MSH) -hormones the anterior pituitary secretes are stimulated and supressed by hormones release by the hypothalamus (releasing hormones and inhibiting hormones) 2)Posterior Pituitary -composed of neural tissue -infundibulum is found in the posterior pituitary 3)Pars Intermedia-third region of the pituitary gland that atrophies during human fetal development and ceases to exist in adults, though some of the cells migrate into the anterior pituitary and persist

Hypophyseal Portal System Blood supply to the anterior pituitary is from the superior hypophyseal arteries. Hypothalamic releasing and inhibiting hormones enter the primary plexus and flow to the secondary plexus in the anterior pituitary by the hypophyseal portal veins Hypothalamic hormones that release or inhibit anterior pituitary hormones reach the anterior pituitary through the portal system NORMALLY: blood goes from heart to artery to capillary to vein to heart Here: Capillary network to portal vein to second capillary network to heart

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Chapter 18: The Endocrine System Neurosecretory cells-clusters of specialized cells that synthesize the hypothalamic releasing and inhibiting hormones in their cell bodies, and package the hormones into vesicles which then go to the axon terminals. Nerve impulses cause the vesicles to undergo exocytosis, and the hormones diffuse into the primary plexus of hypophyseal portal system. Hormones go through the portal veins into the secondary plexus capillaries. [Here, they can act immediately on anterior pituitary cells before the hormones are diluted or destroyed in the general circulation]. Then the anterior pituitary hormones get secreted and go into secondary plexus, then to anterior hypophyseal veins, then general circulation. Then the anterior pituitary hormones travel to target tissues within the body via the general blood circulation. Tropic Hormones-anterior pituitary hormones that act on other endocrine glands Types of Anterior Pituitary Cells and their Hormones 5 types anterior pituitary cells 1) Somatotrophs -secrete Human growth hormone -human growth hormones stimulates other tissues to secrete insulin-like growth factors -Insulin-like growth factors cause general body growth and regulate some aspects of metabolism 2) Thyrotrophs -secrete thyroid stimulating hormones TSH (T3 and T4) -TSH controls secretions and activities of the thyroid gland 3) Gonadotrophs -secrete 2 gonadotrophins Follicle Stimulating Hormone (FSH) Luteinizing Hormone (LH) -stimulate secretion of estrogens and progesterone -stimulate maturation of oocytes -stimulate sperm production -stimulate secretion of testosterone 4) Lactotrophs -Secrete Prolactin (PRL) -stimulate milk production in mammary glands 5) Corticotrophs -secrete adrenocorticotrophic hormone (ACTH) -stimulates the adrenal cortex to secrete glucocorticoids (ex. Cortisol) -may also secrete melanocyte-stimulating hormone (MSH)

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Chapter 18: The Endocrine System

Human Growth Hormone and Insulin-like Growth Factors Somatotrophs are the most numerous cells in the anterior pituitary, thereby making hGH the most common hormone in the anterior pituitary Main Function of hGH: to promote synthesis and secretion of insulin-like growth factors (IGF’s) Tissues that secrete IGF’s: liver, skeletal muscles, cartilage, bones and other tissues -can act locally (like paracrines or autocrines) or enter blood from liver Functions of IGF’s: -cause cells to grow and multiply -decrease the breakdown of proteins, and the use of amino acids for ATP production -thereby increases the growth rate of the skeleton and skeletal muscles during childhood and teenage years -In adults, helps maintain muscle mass and bone mass, and promote healing of injuries and tissue repair -Enhance lipolysis (fat breakdown) in adipose tissue -influence carbohydrate metabolism (spares glucose so it is available to neurons for ATP production in times of glucose scarcity -may also stimulate liver cells to release glucose into the blood Somatotrophs in anterior pituitary release bursts of hGH every few hours, esp during sleep hGH activity is regulated by two hormones released from hypothalamus 1) Growth-hormone releasing hormone (GHRH) 2) Growth-hormone inhibiting hormone (GHIH) -a major regulator of these two hypothalamic hormones is blood glucose levels Ex) Low blood sugarGHRH stimulates secretion of hGHhGH stimulates secretion of IGF’s-speeds up breakdown of liver glycogen into glucose Glucose enters blood Too much glucose Stimulates hypothalamus to release GHIH GHIH inhibits production of hGH Decreases amounts of hGH and IGF’s -glucose breakdown in liver slowed, and release into bloodstream is slowed *secretion of hGH is stimulated by growth hormone-releasing hormone (GHRH) and inhibited by growth-hormone inhibiting hormone FSH and LH together stimulate the secretion of estrogens by ovarian cells LH triggers ovulation

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Chapter 18: The Endocrine System To bring about milk production, LH, estrogen, progesterone, glucocorticoids, hGH, thyroxine, and insulin work together. And oxytocin once stimulated by the baby sucking Breast ouchness before period is caused by high PRL Stress related stimuli (ex. Low blood glucose or physical trauma) also cause the release of ACTH

Posterior Pituitary -does not synthesize hormones -stores and releases two hormones: Oxytocin, and Antidiuretic Hormone The Posterior pituitary is composed of axons and axon terminals of hypothalamic neurosecretory cells (cell bodies in the hypothalamus, axon terminals in the hypothalamic neurosecretory cells in the posterior pituitary) Hypothalamohypophyseal Tract-formed by the axons that run from the hypothalamus to the posterior pituitary Pitiocytes-specialized neuroglia that have a supporting role similar to that of astrocytes Oxytocin and antidiuretic hormone are produced in the hypothalamus and packaged into secretory vesicles, and then transported to the posterior pituitary gland for storage. They are stored there until nerve impulses trigger exocytosis and release of hormones

Oxytocin -function unclear in males and non-pregnant females In pregnant/recently pregnant (just had baby) females, oxytocin affects the mother’s uterus and breasts During Delivery: stretching of cervix stimulates the release of oxytocin, and oxytocin enhances contraction of smooth muscle cells in uterine wall After Delivery: stimulates milk ejection from mammary glands in response to suckling Antidiuretic Hormone (ADH) -acts to retain body water and increase blood pressure -causes the kidneys to return more water to the blood, thus decreasing urine volume -alcohol inhibits the secretion of ADH Osmoreceptors-neurons in the hypothalamus that monitor blood osmotic pressure -activate the hypothalamic neurosecretory cells that synthesize and release ADH The blood carries the ADH to 3 target tissues: kidneys, sudoriferous (sweat) glands, and smooth muscles in blood vessel walls

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Chapter 18: The Endocrine System

THYROID GLAND -butterfly shaped -located just below the larynx (voice box) -composed of right and left lobes (one on either side of the trachea) connected by an isthmus (a narrow passageway) -highly vascularized Thyroid Follicles-microscopic spherical sacs that make up most of the thyroid gland -The wall of each follicle is made up of cells called follicular cells (most of the follicular cells extend into the lumen (internal space) of the follicle) -sometimes the follicular cells are inactive-they get stimulated by the release of TSH (thyroid stimulating hormone) -The thyroid produces 2 hormones: T3 (triiodothyronine) and T4 (thyroxine) →collectively called the thyroid hormones Parafollicular cells (C cells) lie between follicles and produce calcitonin (helps regulate calcium homeostasis- calcitonIN INhibits osteoclast activity-prevents bone breakdown and thereby decreases blood Ca2+ levels) -thyroid gland is the only gland that stores large levels of the hormones it produces-approximately a 100 day supply Thyroid hormones regulate: 1) Oxygen use and basal metabolic rate (BMR) 2) Cellular metabolism 3) Growth and development -increase basal metabolic rate -stimulate synthesis of Na+/K+ pumps/ATPase -increase body temperature (calorigenic effect) -stimulate protein synthesis -increase the use of glucose and fatty acids for ATP production -stimulate lipolysis -enhance some actions of catecholamines -regulate development and growth of nervous tissue and bones Follicular cells also synthesize thyroglobulin (TGB)-is a protein that helps to synthesize T3 and T4 Thyroid hormones are synthesized by attaching iodine atoms to the amino acid tyrosine 1) Basal Metabolic Rate (BMR)-the rate of oxygen consumption under standard or basal conditions (awake, at rest, and fasting) -Thyroid hormones increase BMR by stimulating the use of cellular oxygen to produce ATP -When BMR increases, the cellular metabolism of carbs, proteins and lipids also increases -thyroid hormones also stimulate the synthesis of more sodium-potassium pumps 10

Chapter 18: The Endocrine System

Calorigenic Effect-as cells produce and use more and more ATP, more heat is given off and body temperature rises -thyroid hormones play an important role in regulating body temp 2)Thyroid hormones regulate metabolism -stimulate protein synthesis -increase use of glucose and fatty acids for ATP production -increase lipolysis and enhance cholesterol excretion→ re...