PSL300H1 Study Guide - Final Guide: Insulin Receptor, Adrenal Medulla, Peptide Hormone
PSL3
Te Test Reie
Endocrine System
Lecture 1: Introduction to Physiology
− Physiology is the study of how the body works
− Negative feedback is when a change in a variable is reduced
− Positive feedback is when a change in a variable increases
Lecture 2: Hormones
Hormones: chemical messengers that alter activity of target cells to maintain homeostasis; made in
specific glands where they bind to receptors; action must be terminated
− Protein hormones—most hormones, made in advance, secreted by exocytosis, water soluble,
membrane bound, short half-life
− Steroid hormones—synthesized from cholesterol, diffuses out, water insoluble,
cytoplasm/nucleus bound, long half-life
− Tyrosine hormones (amine)—catecholmines (behave like peptides,
dopamine/norepinephrine/epinephrine, from adrenal medulla, stored in vesicles, SNS), thyroid
hormones (T3 and T4)
− Insulin release—stimulated by glucose
o Glucose enters cell→ metabolized→ ATP goes up → K+ channels close→ cell
depolarized→ voltage channels open→ insulin released
o Insulin reduces glucose (-ve feedback)
− Anterior pituitary hormones
o FLATPEG = FHS, LH, ACTH, TSH, prolactin, endorphins, GnRH
Lecture 3: Receptors and Signaling
Receptors: important for regulating processes like metabolism, homeostasis, growth, blood pressure,
temperature
− Drugs work on receptors
− Hormones signal through receptors
o Binds to receptor, changes conformation, alters activity of intracellular signaling
pathways, and leads to change in synthesis/modification of proteins
− Changes membrane potential
− Agonist—stimulates a receptor
− Antagonist—inhibits a receptor
− Receptors are large proteins that are activated and inhibited
− Can have multiple receptors for one ligand or multiple ligands for one receptor
− Located in cell membrane, cytoplasm and nucleus
− High affinity, saturable, specific, reversible
− Two types:
Intracellular receptors
− Cytosolic and nuclear
− Directly alter gene transcription = genomic effects
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Plasma membrane receptors
G-protein coupled receptors
− Sits in inactive state w/ multiple G-protein subunits
− Alpha subunit has multiple isoforms: G(as), G(ai), G(aq) responsible for signalling
− G(as) = alpha stimulatory, G(ai) = alpha inhibitory, G(aq) = two pathways
− G(as)→adenylyl cyclase→cAMP→PKA→cell response
− G(as) activates adenylyl cyclase
− No PKA phosphorylation, no effects
− G(aq)→PLC→(a) DAG →PKC/(b) IP3→ Ca2+→cellular response
− G(aq) activates phospholipase C, two pathways result
o Activate DAG → PKC
o Activate IP3 → Ca2+ release
Receptor-enzyme receptors
− Ex. Insulin receptor
− Insulin activates two signaling paths: Ras-Map kinase and PI-3 kinase/protein kinase B
− Insulin activates PI3K/MAPK pathways and translocation of GLUT4 to allow for glucose uptake
Receptor-channel
Integrin receptor
Take away points
− Hormone response elements are specific DNA sequences
− Sometimes receptors recruit co-repressors to inhibit transcription
− Only genes with those elements will be repressed
− Fight or flight responses mediated by GPCRs (SNS)
− Epinephrine and norepinephrine have diverse physiological effects via different receptors and
effectors
− Epinephrine increases glycogen breakdown and decreases synthesis
− Epinephrine has multiple receptors, cause multiple responses
Hormone modulation
− Hormone is degraded
− Receptor down-regulated or up-regulated
− Receptor desensitization
− Breakdown of secondary messengers
− Biological effect provides feedback to reduce secretion
Lecture 4: Calcium Balance
Ca2+:
− Intracellular signaling
− Hormone secretion
− Blood clotting
− Neural excitability and muscle contraction
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− Building and maintaining bone
− Three locations of Ca2+:
o Extracellular matrix
o Extracellular fluid
o Intracellular Ca2+
Three hormone control Ca2+:
− Parathyroid hormone (PTH) (increases Ca2+)
o From parathyroid glands
o Stimulus: low plasma Ca2+
o Ca2+ sensing receptor on plasma membrane used to monitor extracellular Ca2+
o When it binds, GPCRs activated, adenylyl cyclase inhibited, PLC activated, PTH secretion
is inhibited
o PTH increases Ca2+ by acting directly on bone and kidney and intestine
o Kidney: increase calcium reabsorption at distal tubule, increase calcitriol synthesis,
decrease phosphate reabsorption at proximal tubule
o Bone: increases CAMP to increase RANKL and decrease OPG expression. More
osteoclasts formed, leading to reabsorption
− Calcitriol (vitamin D3) (increases Ca2+)
o Skin, liver, kidney
o Vitamin D ingested or coming from skin will undergo multiple enzymatic steps
o Calcitriol targets intestine, bone and kidney to increase blood/extracellular fluid calcium
o Binds vitamin D nuclear receptor→increases expression of Ca2+ channels/binding
proteins/transporters in kidney and intestine, RANKL→ increases plasms Ca2+
− Calcitonin (decreases Ca2+)
o Secreted from C cells of thyroid gland
o Peptide hormone
o Stimulus: high plasma [Ca2+]
o C cells also have Ca2+ sensing receptors
o Tones down calcium levels
o Protects the skeleton from Ca2+ loss during pregnancy and lactation
o Reduces activity of osteoclasts (inhibits bone reabsorption)
o Stimulates osteoblasts (deposit calcium)
o Inhibits calcium reabsorption by kidneys
Happens at three target sites:
− Bones (storage)
− Kidneys (adjustment: excretion and reabsorption)
− Digestive tract (absorption)
High Calcium (bones, stones, groans, psychic overtones)
− Bone pain
− Kidney stones
− Slowing of bowels
− Cognitive changes
Low Calcium (CATS go Numb)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Physiology is the study of how the body works. Negative feedback is when a change in a variable is reduced. Positive feedback is when a change in a variable increases. Hormones: chemical messengers that alter activity of target cells to maintain homeostasis; made in specific glands where they bind to receptors; action must be terminated. Protein hormones most hormones, made in advance, secreted by exocytosis, water soluble, membrane bound, short half-life. Steroid hormones synthesized from cholesterol, diffuses out, water insoluble, cytoplasm/nucleus bound, long half-life. Tyrosine hormones (amine) catecholmines (behave like peptides, dopamine/norepinephrine/epinephrine, from adrenal medulla, stored in vesicles, sns), thyroid hormones (t3 and t4) Insulin release stimulated by glucose: glucose enters cell metabolized atp goes up k+ channels close cell depolarized voltage channels open insulin released. Anterior pituitary hormones: flatpeg = fhs, lh, acth, tsh, prolactin, endorphins, gnrh. Receptors: important for regulating processes like metabolism, homeostasis, growth, blood pressure, temperature.
