Chapter 18 - Endocrine System - edited.pdf

Part 1: Introduction to the Endocrine System, Forms of Cell-to-Cell Communication, & 3 Classes of Hormones Part 2: General Overview of Endocrine Organs, and a Deep Look Into the Pancreas     Regulates “long-term” processes via chemical signals known as? Hormones – bind to specific receptors betw...

Part 1: Introduction to the Endocrine System, Forms of Cell-to-Cell Communication, & 3 Classes of Hormones Part 2: General Overview of Endocrine Organs, and a Deep Look Into the Pancreas     Regulates “long-term” processes via chemical signals known as? Hormones – bind to specific receptors between cells relaying information and instructions. An effector’s membrane protein that responds to signals ◦ Ex:Hormones, light, antigens, neurotransmitters, ions Main mechanisms of intercellular communic. ◦ Ex: Epithelial tissues Heart – intercalated disks     Paracrine w/in a tissue – “healing processes” ◦ EX: Eicosanoids Autocrine targets same cell – “WBC stimulation” ◦ Helper T-cell activation! Endocrine Comm. – targets distant tissues via bloodstream – “long-term homeostasis/changes” Neural/Synaptic Comm. – occurs w/in synapses via neurotransmitters – rapid communication that is short lived – “immediate + emergency responses”.  Endocrine Strength of Signal – based on conc. of hormones w/in blood. ◦ IE: many will be held w/in a specific range.  Neural/Synaptic Comm. Strength of Signal – based on frequency of neural signal   Chemical signals, travel in bloodstream, bind specific receptors of effector in a distance. Function: modify cellular activity of effector: ◦ Alter genetic activity – turn on/off ◦ Stimulates metabolic activity – cell more active. ◦ Change membrane permeability – allows entrance or release of substances – leads to cellular response! ◦ MP: Regulates long-term, complex processes  reproduction, digestion, chemical balance, energy levels. Hormones are divided into 3 classes: 1. Amino acid derivatives – tyrosine OR tryptophan 2. Peptide hormones – long chains of amino acids 3. Lipid derivatives – lipid soluble substances.  ◦ Freely pass cell membrane   Small molecules derived from an amino acid? 2 types of amino acid derivatives. AA1) Tyrosine derivatives : ◦ i) Thyroid hormones (lipid soluble) produced via thyroid gland = regulates metabolism of cells. ◦ ii) Catecholamines (water soluble) include:  I] nor- and epinephrine = fight and flight response  II] Dopamine = reward response as NT; many functions (several target cells) as hormone  AA2) Tryptophan (water soluble) derivatives: ◦ i) Melatonin – sleep hormone; regulates day-cycle. ◦ ii) Serotonin – mood enhancer + many others.  Short lived molecules survive minutes to hours         Longer lived hormones compared to AA derivatives, but are still “short-lived” – minutes, hours, days. Lipid Soluble or Water Soluble? WATER SOLUBLE – Meaning? Can’t by-pass cell membrane freely = Binds extracellular receptors. Often produced as prohormones ◦ inactive molecules converted to active hormones before or after secretion. Ex:pro-insulin Are the “primary messenger.” First molecule to start a chemical cascade that results in a response. Series of chemical changes that results in the final cellular response  Lipid messengers: 2 types (lipid soluble), meaning? ◦ Pass cell membrane and bind receptor INSIDE the cell  1) Steroid (MAIN) hormones aka “steroids” -? ◦ Derived from cholesterol; ◦ Long Lived – days to weeks ◦ Must be “bound” to protein when circulating.  2) Eicosanoids [I-coas-a-noids] derived from? ◦ arachidonic acid = 20 carbon fatty acid. ◦ Main function (MF) = paracrine signaling coordinating cellular activity w/in tissues (blood clotting) ◦ a) prostaglandins = regulates many cellular activities  Ex: blood clotting via vasoconstrictors/dilators. ◦ b) Leukotrienes = eicosanoids that stimulates inflammation  Ie: (PARACRINE SIGNALING).    Lipid messengers derived from cholesterol Circulate as “bound hormones” meaning? attached to transport proteins ◦ harder to breakdown; therefore, last longer in circul.  “Main Lipid soluble” hormones so far… ◦ Thyroid hormone & steroid hormones, which are Released by:  Reproductive organs (sex hormones), Adrenal Cortex of adrenal gland (aldosterone, cortisone, and androgens), and Kidneys (calcitriol). ◦ Non-polar molecules that can freely cross plasma membrane when NOT bound to a protein.  Polar hormones that CANNOT pass bi-layer, and therefore bind extracellular receptors. ◦ Receptors that bind hormones OUTSIDE the cell.  ALL PEPTIDE hormones  ALL Amino Acid derivatives except for Thyroid Hormone.  “Free Hormones” – not bound to transport proteins.  Non-polar hormones that freely pass bi-layer, and therefore bind intracellular receptors. ◦ Receptors inside the cells.  All steroid derivative hormones AND Thyroid hormone.  “Bound hormones” – must be attached to transport protein.  Students need to get in habit of categorizing each hormones and knowing “water or lipid-soluble”. Part 1: Introduction to the Endocrine System, Forms of Cell-to-Cell Communication, & 3 Classes of Hormones Part 2: General Overview of Endocrine Organs, and a Deep Look Into the Pancreas    Hypothalamus – Master endocrine gland; receives lots of sensory input and indirectly controls many organs. Pituitary Gland – 2nd in command; receives messages for hypo. and sends info out for slightly more direct control. Thyroid Gland – regulates NORMAL metabolism; important for development.        Adrenal Medulla – emergency metabolism via adrenaline (epi) Adrenal Cortex – salt balance + stress metabolic response. Pancreas – blood glucose regulation. Pineal Gland – sleep cycle regulation. Parathyroid – blood calcium regulation. Heart – reduce BP. Kidneys – produce RBCs + calcium regulation.      Inferior to stomach; superior to small intestine. Endocrine OR Exocrine organ? BOTH! Exocrine cells = pancreatic acini = 99% of pancreatic tissue volume – digestive enzymes. Endocrine cells = pancreatic islets – secrete insulin and glucagon – pancreatic hormones! Main Functions: 1) aid digestion via enzymes, 2) regulate blood glucose levels via insulin + glucagon!  aka islets of Langerhans. = produce hormones? ◦ Insulin and glucagon, function?  Peptide hormone produced by beta cells to lower blood glucose levels (BGLs). ◦ Secreted primarily during + shortly after meals. ◦ Target cells (liver + skeletal muscle) increase glucose and amino acid uptake, utilization, + ATP production. ◦ stim. glycogen, protein, and triglyceride formation.  MPs: Beta cells = insulin when BGLs rise = reduce BGLs = stim. cells to store energy reserves within liver + skeletal muscle.  Mobilizes energy reserves to maintain BGLs during fasting = secreted via alpha cells = insulin’s antagonist = increases BGLs.  Targets liver + skeletal muscle  Stimulates break down glycogen & triglycerides.  Can result in gluconeogenesis = glucose production via noncarbohydrate precursor.  Can you a) identify this histology slide as pancreas? b) distinguish islets vs acinar? c) name hormones secreted by organ? d) overall function of organ?   High BGLs due to faulty glucose metabolism. High levels of glucose in urine = glucosuria = indicator of diabetes. ◦ BGLs so high overwhelms kidney = fails to reabsorb.       2 types: Type I vs Type II? Insulin dependent = beta cells fail to produce functional insulin = 5 – 10% of cases likely genetic = requires injections/pump = often an autoimmune disease Most common = normal insulin, but receptor levels low or do not respond = insulin resistance Associated with obesity (diet related), treated via medication + exercise and dieting. Likely genetic related  High BGLs = exchange + blood flow complications. 1. 2. 3. 4. 5. 6. 7. How does endocrine system differ from nervous system? How do direct, autocrine, paracrine, endocrine, and synaptic communication differ? What are amino acid derived vs peptide vs steroid hormones, & which easily pass the membrane & why? What hormones tend to be bound, and where are the receptors they bind to located? What are free hormones vs bound? Which are long/short-lived? Which bind extracellular/intracellular receptors? What are the main endocrine roles of the following organs: hypothalamus, thyroid, heart, and parathyroid glands? What are the main endocrine roles of the following organs: thalamus, pancreas, adrenal gland, and pineal glands? What is the role of the pancreas, what are the 2 functional regions and their roles, what are the 2 cells and the hormones they secrete? How do insulin and glucagon differ in functions and the cells that secrete them? Which hormone imbalance is related to diabetes? How does type 1 and type 2 diabetes differ? Part 1: The Hypothalamus and Its Hormones Part 2: The Pituitary Gland and the Hormones of the Anterior Pituitary Part 3: Hypophyseal Portal System, Histology of the Pituitary Gland, & the Role of Growth Hormone     via endocrine reflexes – endocrine sensory units that trigger hormone response. (3 stimuli) 1) Humoral “stimuli” – change in extracellular fluid. 2) Hormonal stimuli – hormone stimulates the release (or inhibition) of another specific hormone. 3) Neural stimuli – sympathetic stimulation at the neuroglandular junctions (adrenal medulla).  Most secretion controlled via negative feedback. ◦ hormone release is greatest for initial response and tapers off as body nears normal range.  MP: These 3 diff types of stimuli cause release or inhibition of hormone release.   Master endocrine gland targets 3 organs via 3 ways: (18.5) 1) Anterior pituitary (via regulating hormones (RH) [either releasing or inhibiting] via blood vessels ◦ Releasing hormones stimulate production & secretion of hormones made by anterior pituitary. ◦ Inhibiting hormones reduce production & secretion.  2) Posterior Pituitary – axon terminals storing hormones of HT reach blood vessel in Post. Pit.  3) Adrenal medulla (via sympathetic nerves (ANS) – stimulates release of hormones made by adrenal medulla, which are?.      1) Releasing hormones➔ target ant. pituitary ➔ increase production and release of hormones. 2) Antidiuretic ➔ kidneys ➔ increases water hormone (ADH) retention/reabsorption = increases BP when BP low. 3) Oxytocin ➔ uterus ➔ contractions (childbirth) ➔ breasts ➔ release milk Rare positive feedback loop!      Hormones that target the ant. pituitary resulting in the production and release of a specific hormone. Thyrotropin-releasing hormone – stimulates production and release of TSH; CRH – stimulates release of ACTH by ant. pit. GnRH – stimulates release of FSH and LH, hormones that target the gonads. STUDY TABLE 18.2 – all hormones; (18.5 b for lab) Part 1: The Hypothalamus and Its Hormones Part 2: The Pituitary Gland and the Hormones of the Anterior Pituitary Part 3: Hypophyseal Portal System, Histology of the Pituitary Gland, & the Role of Growth Hormone       Vice President of Endocrine Releases 9 PEPTIDE hormones that bind? Extracell. Receptors ➔ cAMP as 2nd messenger. Inferior to HT; lies within sella turcica of sphenoid. Connected to HT via infundibulum. 2 distinct lobes (18.5), which are?  Anterior pituitary produces & secretes 7 horm.; 3 distinct histological regions:  posterior pituitary secretes 2; produces 0  1 distinct regions: ◦ Pars nervosa   Stimulated by releasing hormones Ex: TRH, CRH, GnRH; Inhibited by inhibiting hormones. STUDY TABLE 18.2 – all hormones; (18.5 b for lab)      Unmyelinated axons of hypothalamic neurons. Stores & releases (DOESN’T PRODUCE) 2 hormones? Supra-optic nuclei – produce ADH = vasopressin – helps retain water/increase of blood pressure. Paraventricular nuclei – produce OXT = stimulates uterine contraction; stimulates milk ejection. Inferior HPS = carries hormones of posterior pituitary into circulation  Membrane proteins that bind specific hormone resulting in cellular changes ◦ No receptor = no effect!     Diff. cells have diff. receptors (many kinds) & diff receptors cause diff responses. Tissues have unique combination of receptors ◦ This allows 1 hormone to have varying effects from 1 tissue to another 2 locations for receptors on cells? 1) Extracellular receptors – receptors on the surface of the plasma membrane (PM) surface ◦ water soluble (peptide + AA) hormones bind here.  2) Intracellular receptors – receptors on membranes inside the cell ◦ lipid soluble (steroid + thyroid) hormones bind here Part 1: The Hypothalamus and Its Hormones Part 2: The Pituitary Gland and the Hormones of the Anterior Pituitary Part 3: Hypophyseal Portal System, Histology of the Pituitary Gland, & the Role of Growth Hormone Set of blood vessels connecting hypothalamus to the pituitary gland. (fig 18.7)  Unique fenestrated capillaries (large pored capillaries) allow hormones released by HT neurons to enter blood.  Regulatory hormones travel via the superior HPS here to stimulate ant. pituitary.  Inferior HPS = carries hormones of posterior pituitary into circulation   Important for quick regulation of hormones via the master glands  4 unique histological layers ◦ 3 for anterior (pars distalis, intermedia, & tuberalis) ◦ 1 for posterior (pars nervosa)    Fig 18.8 illustrates hypothalamic regulation & includes release hormones I expect you to know. HT has lot of regulating hormones impacting pituitary. Represents negative feedback  Fig 18.9 illustrates pituitary regulation throughout the body. Pituitary = Vice President     Too much Growth Hormone (GH) during childhood leads to – Gigantism (left) Dwarfism (middle) Too little GH leads to? High levels during adulthood? Acromegaly (right) GH ➔ production of somatomedins or insulin-like growth factors that contribute to growth as well. Part 1: Thyroid Gland, Histology, Hormones, and Regulation. Part 2: Thyroid Hormone Production, the Parathyroid Glands, and Calcium Regulation. Part 3: The Adrenal Gland, Its Histology and Hormones, and Adrenal Gland Imbalances.    Inferior to thyroid cart. (Adam’s apple) of larynx. 2 lobes connected via isthmus. Composed of thyroid follicles. ◦ Hollow spheres lined by simple cuboidal epithelium.   colloid – viscous fluid w/in follicle filled w/Thyroglobulin [TGB], a protein precursor to thyroid hormone produced by follicle cells. Cells surrounded by capillaries delivers/receives nutrients, horm., & wastes.  Can you identify this as the “Thyroid gland”, spot the “C- vs follicle-cells”, know the hormones released, identify the colloid, know what’s stored in the colloid    Pituitary, peptide hormone – stimulates iodine absorption + T3 & T4 production & secretion. Released when levels of T3 and T4 are below normal range. Low levels of T3 & T4 or of TSH results in mental & physical sluggishness  In children, essential for normal development: ◦ Skeletal, muscular, and nervous systems.  If TSH in the blood were high but levels of T3 & T4 were low, what does this indicate?  TSH receptor issue   Most cells; binds intracellular receptors (lipid-sol.) Functions related to? ◦ A) Energy usage/metabolism in some tissue  Processing of lipids, carbs, and proteins ◦ B) Regulation of body temperature ◦ C) Growth & development, esp. for children!  Bone, hair, teeth, connective tissue, and neural tissue.  Important element for its formation? ◦ Iodine;   lack of iodine can lead to? Goiter TH formed w/3 iodine ions=T3or Triiodothyronine. TH formed w/4 iodine ions = T4 or Thyroxine.   Increases metabolic activity by: 1) Elevate oxygen + energy consumption ◦ raises body temperature.  2) Increase heart rate + force of contractions. ◦ raises blood pressure – quicker distribution.   3) Increase sensitivity to sympathetic stimulation. 4) Stimulates RBC formation ◦ Enhances oxygen delivery.    5) Stimulates other endocrine tissues. 6) Accelerates turnover of minerals in bone. Has a calorigenic effect – consumes energy and releases heat! Part 1: Thyroid Gland, Histology, Hormones, and Regulation. Part 2: Thyroid Hormone Production, the Parathyroid Glands, and Calcium Regulation. Part 3: The Adrenal Gland, Its Histology and Hormones, and Adrenal Gland Imbalances.   1) Iodine Ions actively transported into follicle cells 2) Follicle cells synthesize thyroglobulin - Tyrosine containing globular protein + TH precursor. 18.11 ◦ Fig.18.11 3) TGB + iodine diffuse to apical surface of follicle cells; tyrosines of TGB gets iodinated      4) Iodinated TGB is exocytosed into follicle lumen (2-4 months). 5) w/in colloid, TGB undergoes chemical reactions resulting in globular T3 and T4 6) Globular T3 + T4 w/in TGB are endocytosed 7) w/in follicle cell, TGB broken down into individual T3 & T4 hormones via lysosomes. 8) T3 & T4 diffuse into blood bind to Thyroxine-binding globulin and transported appropriately.  1) Get Iodine, 2) Form TGB, 3) Combine iodine and TGB  4) Transport iodinated TGB into colloid, 5) enzymes convert TGB to globular T3 and T4 w/in colloid.  6) Globular T3 and T4 and endocytosed, 7) lysosomes break globular T3 and T4 into individual T3 and T4 hormones.  8) T3 and T4 diffuse into blood, 9) T3 and T4 bind thyroxine-binding globulin or a transport protein.     Hyperthyroidism – high levels of thyroid secretions Symptoms: increase metabolic rate, high body temp., weight loss, increased appetite, copious sweating, rapid heart rate, high BP, abnormal EKG, weak muscles, hyperactivity, insomnia, + others. Hypothyroidism – low levels of thyroid secretions Symptoms: decrease metabolic rate, low body temp., weight gain, reduce appetite, low sweat and oil secretions causing dry skin, reduced heart rate and BP, enlarged heart, sluggish movement w/weak, untoned muscles, apathetic, always fatiqued, + others.   Produce and secrete calcitonin (CT)? Regulates Ca2+ levels in blood & body fluids by? ◦ Inhibits osteoclasts – slows release from bone. ◦ Stimulates osteoblasts – increase uptake from blood. ◦ Increases excretion of Ca2+ at kidneys.  Net affect of calcium in blood? ◦ Decrease in available calcium in blood.   Glands embedded in posterior surface of thyroid. Chief cells secrete parathyroid hormone. (18.12) ◦ When blood Ca2+ levels are low. What does it do?  1) Stimulates osteoclasts/inhibits osteoblasts. ◦ Accelerates mineral turnover; releasing Ca2+ off bone ◦ Considered calcitonin’s Antagonist?   2) Enhances Ca2+ reabsorption. at kidney 3) Stimulates formation and secretion of Calcitriol by kidneys. ◦ Compliments PTH ◦ Increase uptake of Ca2+ via digestion.    Calcitonin increases bone absorption + calcium secretion, which decreases blood Ca2+ concentration. PTH breaks bone down releasing Ca2+ + reabsorb @ kidney = increases blood Ca2+ concentration. Calcitriol is similar to PTH but increases Ca2+ conc. via absorption at intestines! Part 1: Thyroid Gland, Histology, Hormones, and Regulation. Part 2: Thyroid Hormone Production, the Parathyroid Glands, and Calcium Regulation. Part 3: The Adrenal Gland, Its Histology and Hormones, and Adrenal Gland Imbalances.    Located superiorly to each kidney. (fig. 18.14) 2 regions: 1) Adrenal cortex (superficial) ◦ Stores lipids (high cholesterol and fatty acids) ◦ Manufactures steroid hormones (3 types).  2) Adrenal medulla (inner region) ◦ Produces epi and norepinephrine (catecholamines). ◦ Controlled via sympathetic division of ANS  1) Identify as adrenal gland? 2) Identify each region? 3) Identify a hormone released at each region? 4) know the function of each hormone?    Hyposecretions = low level of secretions cause by removal of gland or loss of function. A) Mineralocorticoids – hyponatremia (low Na+ levels), hyperkalemia (high K+ levels), acidosis, low BP, tremors of skeletal muscle, and polyuria. B) Cortisol – removal of gland or loss of function ◦ Hypoglycemia (low blood glucose levels), depressed immune system, loss of appetite, nausea, vomiting, weight loss.  Addison’s Disease – low levels of both – ie: major issues with the adrenal cortex. ◦ Weight loss, muscle weakness, low BP, constant fatigue   Hypersecretion = high level of secretions A) Mineralocorticoids – caused by tumor in gland or aldosteronism. ◦ Slight hypernatremia, hypokalemia, alkalosis, high BP, weakness in muscles, and acidic urine.  B) Cortisol – tumor in gland or Cushing Syndrome (includes hypersecretion of androgens) ◦ Hyperglycemia – leads to diabetes mellitus, depressed immune system, tissue protein destruction leading to muscle weakness & atrophy, impaired wound healing, re-distribution of adipose (to face, neck, and abdominal region). ◦ Emotional effects of euphoria & depression.    Pinealocytes (cells) secrete? Melatonin, which? Influences circadian rhythms? ◦ (sleep/wake cycles)   In humans, peak levels @ night ➔ drowsy lowest levels @ noon (day) ➔ awake Part 1: Levels of Hormone Interactions, Hormones from Other Organs, and General Adaptive Syndrome Part 2: Lipid Soluble vs Water Soluble Hormone Differences and Functionality    Hormones cause different responses on tissues and may have unique effects when other hormones are present. Effects of 2 differing hormones are:1) antagonistic, 2) synergistic, and 3) permissive, meaning? Opposite/opposing effects like? ◦ PTH + Calcitonin; insulin + glucagon  Additive effects like? ◦ PTH + Calcitriol; ADH + aldosterone  The hormone of interest only works in presence of another hormone. ◦ Epi- and norepinephrine require normal levels of thyroid hormone.      Many organs have secondary endocrine functions. Kidney = 1o = waste removal/urine formation 20 = Calcitriol, erythropoietin (EPO), and renin production. Stimulates effects of PTH, stimulates osteoclasts, + increase calcium absorption via intestines. Stimulates red blood cell (RBC) production. ◦ stimulated by low O2 levels in kidney.   Enzyme that stimulates angiotensin II ➔ stimulates ADH and aldosterone release ➔ increase BP. (Details next page) Intestines - 1o = digest and absorb nutrients 20 = secrete hormones that regulate digestion   Heart monitors & generates? Pressure: produces natriuretic peptides (ANP/BNP)? ◦ Opposes angiotensin II, meaning? ◦ Decreases BP when blood volume and/or blood pressure are high. How? ◦ Increase output or stimulate/increase urination.  Inhibits “aquaporin” production that occurs in presence of ADH.  Thymus function? ◦ Site where T-cells mature; T-cells? ◦ Type of lymphocyte of adaptive immunity; ◦ Produces & secretes thymosins = thymic hormones that stimulate T-cell maturation.  Testes = produce testosterone = steroid hormone  development of sex characteristics    Primary develop as fetus; secondary at puberty sex drive, bone & muscle growth + spermatogenesis Ovaries = Estrogen & Progesterone (steroids). ◦ development of uterus and vagina (fetus). ◦ Body hair, + follicle/egg development (puberty)  Progesterone production (corpus luteum). ◦ mammary gland development (puberty) ◦ Maintains uterus – lack of pro = menstration (puberty).  Aka the stress response = pattern of hormonal and physiological adjustments due to stress (18.20). ◦ Broken down into 3 phases  1) Alarm Phase – “everyday stress” – sympathetic stimulation resulting in mobilization of energy reserves – cause by epi- and nor-epinephrine. ◦ Catecholamines (epi and nor) = water soluble = short lived response  2) Resistance Phase – stress longer than few hours – ALL energy hormones in play including steroid hormones from adrenal gland = longer lasting effects – reserves become severely depleted. Part 1: Levels of Hormone Interactions, Hormones from Other Organs, and General Adaptive Syndrome Part 2: Lipid Soluble vs Water Soluble Hormone Differences and Functionality  Hormones released in cir. unattached to protein.  Hormones that circulate attached to a transport protein. ◦ Water soluble hormones = peptide derivatives + catecholamines + tryptophan derivatives ◦ Remain functional for less than 1 hour ◦ Lipid soluble hormones + thyroid hormone ◦ Remain functional for longer periods.    Regardless of type, 2 processes can occur: 1) Bind to receptors ON target cells (effectors) causing a response/performing its function. 2) Broken down ◦ Recycled by liver OR removed by kidneys ◦ Destroyed by enzymes in plasma or interstitial fluid.  Think acetylcholinesterase   Steroid Hormones & Thyroid hormones (18.4) Activate genes for specific protein synthesis. ◦ Ex: testosterone, progesterone, estrogen (sex hormones), cortisol, and aldosterone.  a] activates genes/controls rates of transcription & metabolism via enzyme production. Or b] stimulates ATP production  Targets most cells; important for cell development.  MP: Lipid soluble hormones function by binding intracellular receptors, which often results in “gene activation”.  ALL water-soluble hormones ◦ Peptide hormones, catecholamines, and trypto: why? ◦ Not lipid soluble because? ◦ Large, polar, hydrophilic molecules  Requires 2 messengers (18.3) ◦ 1) First (indirect response) and 2) Second messengers  Peptide hormone that binds PM receptor & activates G protein. ◦ chemical intermediate that responses to 1st messenger & activates the second messenger.  Cytoplasmic molecule(s) that carries out actual response ◦ Activate genes, increase or decrease metabolism, etc     production of LOTS of second messengers (can be diff) in cell via activation of G proteins Based on intracellular enzymes, amplification can occur: big response to low horm. concentration. Cells influence responses by regulating receptors. Down regulation - decrease in # of hormone receptors when hormone conc. high. ◦ Cells becomes less sensitive. ◦ Dramatic decrease of sensitivity? ◦ Diabetes  Up-regulation - increase in # of effector receptors due to low hormone conc. ◦ Cell becomes more sensitive. ◦ Ex: Ovulation – LH receptors    Cytoplasmic chemical msnger (enzymatic activator, inhib. or coenzyme) that leads to cellular response. Ex: Calcium as Secondary Messenger (Msg) 1) Activated G Protein – stimulates opening of Ca2+ ion channel or release via intracellular components  Calcium Stimulates? ◦ Neurotransmitter (NT) release ◦ Muscular contraction ◦ Binds with/activates Calmodulin   Activates cytoplasmic enzymes Main Points (MPs): ◦ Activation of G protein → stimulates intracellular conc. of calc. → calc. has many functions ◦ Main func. = actives Calmodulin   An ATP derivative that alters cellular activity based on intracellular conc. 1) Activated G Protein – increases or decreases conc. of cAMP levels intracellularly depending on enzyme available. ◦ Excitatory effects = increase cAMP; Inhibit = decrease  cAMP increases when G-protein activates adenylate cyclase ➔ ◦ Converts ATP to cAMP.   cAMP – a) activates a Kinase – an enzyme that phosphorylates (activates) another molecule by attaching a high energy phosphate group to it. b) opens ion channels  When G-protein activates phosphodiesterase (PDE) ◦ Breaks cAMP down to AMP ➔ less cAMP = decreased enzymatic activity = decreased cellular activity  MPs of cAMP ◦ High conc. = more activity. ◦ Conc. increased via G-protein activation of adenylate cyclase  Note: “First messengers” = epi + norepi., calcitonin, PTH, etc ◦ Low Conc. of cAMP = less activity ◦ Decreased via activation of phosphodiesterase  Note: epi and norepi.