10/20/2015scnm, phys 612, introduction1 phys 612, endocrinology: introduction

*SCNM, PHYS 612, Introduction*PHYS 612, ENDOCRINOLOGY:INTRODUCTION

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*SYLLABUS

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Homeostasis:Regulatory SystemsNervousEndocrine

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*What Endocrine System DoesHomeostasisi.e., Water & ElectrolytesGrowthEnergy/MetabolismReproductionDefenseDirect vs Indirect/Permissive

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Definitions:Endocrine:Exocrine:Hormone:Paracrine Factor:Autocrine Factor:

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Types of Hormones:

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Water Soluble (Polar):PeptidesEx: Antidiuretic Hormone (ADH)ProteinsEx: Growth Hormone (GH)Amino AcidEx: Epinephrine

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Lipid Soluble (Non-Polar):SteroidsEx: CortisolAmino AcidEx: Thyroid Hormone, Thyroxine (T4)EicosanoidsEx: Prostaglandins, Thromboxanes, Leukotrienes

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Mechanism of Hormone Action:

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*HORMONE ACTIONTake out a piece of paper and answer the following question.

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*How does a cell in the adrenal cortex know to respond to adrenocorticotrophic hormone (ACTH)?

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Receptors:Specificity:Affinity:KD = Half-SaturationCapacity:

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Receptors:LIGANDAGONISTANTAGONIST

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Water Soluble Hormones:Membrane Protein:Second Messenger:Up/Down Regulation of Proteins Already Present:Primarily by Phosphorylation/ DephosphorylationGene Regulation (Secondary)

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Receptor Types:SerpentineSingle Transmembrane Ex. Insulin ReceptorCytokine (Growth Hormone/Prolactin)Guanylyl Cyclase-Linked

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Second Messenger Systems:

SCNM, PHYS 612, Introduction

Second Messengers Used by Serpentine Receptors*SCNM, PHYS 612, Introduction*

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*SCNM, PHYS 612, Introduction*Cyclic-AMP:Ligand binds to ReceptorReceptor linked to Adenylcyclase by G-proteinIncrease production of cAMPActivation of A-KinasePhosphorylate proteinActivate/Inhibit EnzymesActivate Transcription

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Phosphoinositol:Ligand Binds to ReceptorG-protein linked to phospholipase C (PLC)PLC breaks polyphosphotidylinositol into diacylglycerol (DAG) and inositol triphosphate (IP3)

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Phosphoinositol:IP3 Stimulates Release of Ca++ from ERCa++ Then:Stimulates SecretionMuscle ContractionBinds to CalmodulinCa-Calmodulin Activate CaM-KinaseDAG Activates C-KinaseSome forms of C-Kinase Require Ca++ as a Cofactor

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Phosphoinositol:Kinases (C-Kinase & CaM-KinasePhosphorylate ProteinPhosphorylate Transcription Activating Factors

SCNM, PHYS 612, Introduction

Second Messengers Used by Receptors with a Single Transmembrane Domain *SCNM, PHYS 612, Introduction*

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Calcium-CalmodulinCytoplasmic Ca ++ IncreasedReceptor Linked to a Ca++ Channel in MembraneCa ++ Binds to CalmodulinCa-Calmodulin Activates CaM-KinaseCaM-KinasePhosphorylates ProteinPhosphorylates Transcription Factors

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Cyclic-GMP:Membrane Bound Guanylyl CyclaseLigand Binds to ReceptorReceptor Coupled to Guanylyl CyclaseIncrease Intracellular cyclic-GMPActivate G-KinasePhosphorylate Proteins

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Cyclic-GMP:Soluble Guanylyl CyclaseLigand Binds to ReceptorReceptor Opens Ca++ ChannelIncreased Intracellular Ca++Ca++ Activates NO-Synthase NO Activates Soluble Guanylyl CyclaseIncrease Intracellular cyclic-GMPActivate G-KinasePhosphorylate Proteins

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Tyrosine KinaseLigand Binds to ReceptorReceptor Contains a Tyrosine KinaseKinase ActivatedKinase Phosphorylates Protein

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*CYTOKINE RECEPTORLigand Binds to 2-ReceptorsEach Receptor then Binds with a Cytoplasmic Protein (JAK-2)JAK-2 is a Tyrosine KinaseBinding to Receptor Activates JAK-2JAK-2 Then Phosphorylates ProteinsEx. GH & PRL Receptors

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Membrane Receptor DegradationReceptor-Mediated EndocytosisClathrin Coated PitsEndocytosisLysosomal Digestion of LigandReceptors Returned to Membrane Surface

SCNM, PHYS 612, Introduction

LIPID SOLUBLE HORMONE RECEPTORS*SCNM, PHYS 612, Introduction*

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*SCNM, PHYS 612, Introduction*Cytoplasmic/Nuclear ReceptorsLigand binds to receptorHormone-receptor complex attaches to another hormone-receptor complexDimer then binds to DNA.Stimulate or inhibit mRNA production

SCNM, PHYS 612, Introduction

Cytoplasmic/Nuclear Receptors (Cont.)Hormone-receptor complex binds cofactorsCofactors modify action of hormone-receptor complex on mRNA production*SCNM, PHYS 612, Introduction*

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Membrane Receptor*SCNM, PHYS 612, Introduction*

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Review Steroid/Thyroid Hormone ReceptorsCytoplasmic/Nuclear ReceptorsLigand bindsDimer & move to nucleusModulate mRNA productionMembrane ReceptorsSecond Messenger*SCNM, PHYS 612, Introduction*

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CONTROL OF ENDOCRINE SECRETION*SCNM, PHYS 612, Introduction*

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*SCNM, PHYS 612, Introduction*Negative FeedbackMaintains level near a set pointResults in small oscillations about the set point Ex: Thermostat/HeaterEx: Blood Glucose

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*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*NEGATIVE FEEDBACKPANCREASLIVERGLUCOSETIMEGLUCAGONBLOOD GLUCOSE

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Positive FeedbackRare Because It Results in a Runaway ConditionDam BreakingServes to Signal a Specific EventOvulationServes to Signal the Continuation of a ProcessLactationMust Have A Brake!!!

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*POSITIVE FEEDBACKLHTIMEPITUITARY GLANDOVARYLHE2

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*POSITIVE FEEDBACKLHTIMEPITUITARY GLANDOVARYLHE2

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*POSITIVE FEEDBACKLHTIMEPITUITARY GLANDOVARYLHE2

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*POSITIVE FEEDBACKLHTIMEPITUITARY GLANDOVARYLHE2

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*POSITIVE FEEDBACKLHTIMEPITUITARY GLANDOVARYLHE2

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*POSITIVE FEEDBACKLHTIMEPITUITARY GLANDOVARYLHE2

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Factors Affecting a Hormones Plasma ConcentrationSecretionTransportMetabolismExcretion

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*Secretion:Pulsatile SecretionTonic vs EpisodicRhythmsUltradianCircadianMonthlySeasonalDevelopmental

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*SCNM, PHYS 612, Introduction*TransportPolar/Water soluble:Non-Polar/Lipid SolubleTransport ProteinsEx: Thyroid Binding GlobulinNon-Specific Protein BindingEx: AlbuminFree Hormone LevelsWhat Counts is the Amount of Hormone Available to the Cell

SCNM, PHYS 612, Introduction

*SCNM, PHYS 612, Introduction*MetabolismLiverOther

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*SCNM, PHYS 612, Introduction*ExcretionKidneyFece