PGY 300 5st EditionExam # 6 Study Guide Lectures: 1 - 14Lecture 1: Hormones and SignalingHormone:- Chemical produced in specific cells- Transported – blood or ECF- Activates signaling in specific targets- Influences homeostasis or developmentFunction:- Inputo Endocrine tissue o Hormone- Target tissueo Receptor o Signal response- Feedback o Pos or neg.Two major hormones:- Peptides/proteinso Made form amino acidso Small: 3 amino acidso Hydrophilic- Steroidso Made from cholesterol o Similar structureso Hydrophobic Hydrophobic vs. Hydrophilic - Hydrophilic: loves watero Most protein hormoneso Soluble - Hydrophobic: fears watero Steroid hormoneso Insoluble in watero Soluble in lipids - Blood & ECF – aqueous - Membranes- lipids (hydrophobic)Steroids require hydrophilic binding proteinsAmide hormones derived from tyrosine- Thyroid hormones - Catecholamineso Dopamine o Norepinephrineo Epinephrine- Combine aspects of both protein & steroid Lecture 2: Endocrine Signaling Endocrine system: cell to cell communication s- Directo Gap junctionso Contact o Autocrine/paracrine- Distant chemical (endocrine)- Nervouso Neurotransmittero Neurohormone - 3 in endocrine syst. – neurohormone, autocrine/paracrine, distant chemicalParacrine & autocrine signaling- Less common for hormones- Autocrine signals: same cells, hormones released & bind receptors on to cells- Paracrine signals o Diffuse to adj. cellso Hormones in interstitial fluids o Doesn’t really enter bloodstream, diffuse in interstitial fluid to get to adj. cellsSignal transduction:- Target defined by receptor- Hormone binding to receptors initiates a signal- Steroid hormones: cytoplasmic or nuclear receptorsProtein hormone signals:- Bind to cell surface receptors- 2 mains classes: o G-protein coupled: amplifier enzyme o Tyrosine kinase: TK part of receptor, phosphorylates proteinsProtein hormones; some steroids: cell surface receptors- Direct modification of proteins- Seconds to minutes- Fast responseSteroids & proteins: nuclear/cytoplasmic or cell surface receptors- Slow response- Transcription of DNA: > 1 hr -> translations& processing > many hoursLecture 3: Regulations & control of hormone activity Synthesis: all hormonesRelease: only proteinsRegulation of steroid synthesis: - Gene expression of steroidogenic enzyme, more enzyme more steroid- Modification of steroidogenic enzyme activity, make more & work better- KinasesConcentration: how much is made- Big glands = lots of hormones, high concentration -> broad responds- Steroids always come from big glands- Proteins from small glands or few cells in endocrine tissue, low concentration -> limited responseHormone persistence: - Determine by half-life & metabolic clearance rate- Steroids > proteins - Metabolic clearance rate: rate which hormone is removed from circulation Metabolic clearance of steroids:- Inactivated in any tissueo Soluble metabolite o Excreted o Can be metabolized in kidney - Liver o Chemically modified o Eliminated in bileMetabolic clearance of protein hormones:- Blood stream o Protease can inactivate o Metabolized in kidneys- Recovered as amino acids- Some secreted in urineMultiple hormones at the target:- Antagonism: work against- Synergy: sum > parts- Permissiveness: o Specific input required o Hormone or other inputReceptor diversity dictates target response- Alpha1 receptors locate in intestine, bladder, reprod. Organs- Beta1 receptors locate heart, lungsMost hormones are regulated by negative feedback- Neg. feedback: response inhibits further input, homeostasis- Pos. feedback – ex: pregnancy Lecture 4: Inputs & CNS integration Simple input for simple homeostatic response - Input sensed by endocrine tissue - Low lvls of Ca -> hormone release- High lvls Ca -> inhibitedComplex stimuli require the CNS- 2 distinct endocrine tissue- anterior pituitary & posterior pituitary Posterior pituitary:- Neurohormones o Vasopressin: BP & fluid volumeo Oxytocin: uterine contraction &lactation Anterior pituitary: - Neurons make regulatory neurohormones- Center of complex endocrine control- Hypothalamic-pituitary axis (HPA)o Almost neg. feedback Lecture 5: Introduction to Metabolism Energy in = energy out Metabolism = anabolism +catabolism - Anabolism: o Synthesis of large molecules from small moleculeso Require energy inputo FED state- Catabolism:o Synthesis of small molecules from large molecules o Energy releasedo FASTED stateIf a pathway is stimulated by insulin it is anabolic Gluconeogenesis -> de novo (new) glucose synthesis - Most tissues make ATP by beta oxidation of FA- High lvls of beta oxidation in liver -> ketones or ketone bodiesLipid transport & storage- Hydrophobic - Stored as triglycerides in lipid droplets inside cells- Need carrier proteins in blood o Chylomicrons (FED)o VLDL (FED)o Albumin (FASTED), carrier protein Tissue metabolism is specialized Users: - Brain (CNS)o Requires glucoseo Highest priority - Skeletal m.o Biggest glucose user, 75% total o Power muscle contraction o Stores & uses fats at restGivers: - Liver:o Stores & makes glucoseo Supplies CNSo Glucose to fats for storage- Adipose:o Fat storage siteo Comes from excess- lipids, glucose Lecture 6: Insulin & Glucagon Endocrine pancreas:- Insulin & glucagon production - Exocrine makes digestive fluids/enzymes- Main target- liver- Alpha cells: glucagon - Beta cells: insulin Fed state: insulin Fasting state: glucagon Control of insulin secretion - Increase blood glucose is most powerful How target cells respond to insulin - Insulin binds to tyrosine kinase receptor- Receptor phosphorylates insulin-receptor substrates (IRS)- IRS-P activates second messenger pathways- GLUT4 transport (muscle & adipose)- Activation of anabolic pathwaysGLUT4- muscle & adipose: regulated transport GLUT2- liver: transport not regulated Insulin vs glucagon- Glucagon: limitedo Catabolism for glucose mobilization o Major target: livero Minor target: adipose- Insulin: widespread o Anabolism of glucose: liver, muscleo Anabolism of lipids: all tissues, long term storage in adiposeo Inhibits glucoseo Anabolism of proteins in all tissueso Cellular growth& proliferation Lecture 7: DiabetesHyperglycemia: blood glucose too high Type 1 diabetes:- Insulin deficiency - Autoimmune destruction of beta cells, Islet of Langerhans- Blood glucose characterize diabetesType 2 diabetes:- Insulin resistance- Excess insulin - Associated with obesity - Treatment: prevent hyperglycemia, control lifestyleLecture 8: Regulation of Long-term