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    Mechanism of Hormone Action

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    Mechanism of Hormone Action

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    Hitha
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    Mechanism of Hormone action

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    4 views38 pages

    Mechanism of Hormone Action

    Uploaded by

    Hitha

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 38

    HORMONE ACTION

    Specific Learning
    Objectives
    Hormones – Definition, Types &
    Classification with egs.
    Mechanism of action of Group 1
    and Group 2 hormones in detail.
    Hormone
    A hormone is a:
    chemical substance produced in the
    body
    by an organ
    Binds to receptors on cell surface or
    within
    Types of signalling
    Important organs producing
    hormones
    Pituitarygland
    Adrenal gland
    Thyroid gland
    Parathyroid gland
    Pancreas
    Testes and ovaries
    Classification
     Based on Chemical nature & solubility
    properties:
    1. Polypeptide or Protein hormones
    2. Steroid hormones
    3. Derivatives of amino acids
     Based on Mechanism of Action:
    1. Group I Hormones
    2. Group II Hormones
    Polypeptide vs Steroid
    POLYPEPTIDE HORMONES STEROID HORMONES
    1 hormones
    Water soluble, Hydrophilic Lipid soluble, lipophilic
    .
    2 Circulate freely in plasma Circulate in plasma,
    . as a active whole reversibly bound to
    molecule or as inactive transport proteins. For
    fragments eg: TBG, TBPA, CBG
    etc..
    3 Half life is very short – 10 - Half life is longer – 30 -
    . 30 mins. 90 mins.
    4 Acts through cell surface Acts by binding to
    . receptors. intracellular receptors
    either in
    cytoplasm/nucleus.
    5 Egs: Glucagon, ADH, Egs: Glucocorticoids,
    . Calcitonin, Estrogens, Androgens,
    Amino Acid Related
    hormones
    Thyroid hormones &
    Catecholamines are the
    hormones that are derived from
    amino acid tyrosine.
    Group I Hormones
    1. Hormones that bind to intracellular receptors.
    2. Lipophilic in nature
    3. Bind to certain carrier proteins like albumin
    while being transported in the blood.
    4. Biological t1/2 is longer (few hrs –few days).
    5. Their receptors are located within the cell –
    cytoplasm/nucleus.
    6. Hormone receptor (HR) complex enters into
    the nucleus and binds to the DNA and causes
    selective gene expression.
    7. Egs: Steroid hormones, Thyroid hormones etc..
    Mechanism of action
    Hormone response occurs in 4
    stages:
    1. Binding to intracellular receptors
    2. Activation
    3. Binding to Hormone responsive
    elements
    4. Gene expression and protein
    synthesis.
    Group II Hormones
    1. Hormones that bind to cell surface
    receptors
    2. Hydrophilic in nature.
    3. Transported in circulation in free form.
    4. Biological t1/2 is very short (few seconds
    to few minutes).
    5. HR complex stimulates the release of
    certain molecules known as second
    messengers within the cell which exert the
    biological actions.
    6. Group II hormones are further classified
    nd
    GROUP II HORMONES
    1. Hormones that use cAMP as 2nd
    messenger: FSH, LH, TSH, ACTH, calcitonin
    ,CRH, Beta HCG, ADH, Glucagon,
    Epinephrine, MSH, PTH etc..
    2. Hormones that use cGMP as 2nd
    messenger: Atrial natreuretic factor, Nitric
    Oxide, Visual Pathway.
    3. Hormones that use phosphatidyl
    inositol or calcium as 2nd messenger:
    TRH, GnRH, Oxytocin, Vasopressin, Gastrin
    etc..
    4. Hormones that use kinase/phosphatase
    cascade as the 2nd messenger:
    GH, INSULIN, PROLACTIN.
    Mechanism of Action
    Hormone response occurs in four
    stages:
    1. Binding of hormone to receptor.
    2. Activation of G- proteins
    3. Generation of 2nd messengers
    4. Protein phosphorylation.
    G protein receptor
    GPCRs have extracellular hormone
    binding domain, transmembrane
    domain and intracellular domain.
    It’s a 7 transmembrane helix
    receptor also called serpentine
    receptor.
    G Protein
    Its composed of three subunits, α,β
    .
    and γ subunits which are linked to a
    GDP when in inactive state.
    When activated it gets bound to GTP,
    to form α GTP and βγ subunits.
    The dissociated α GTP subunit with
    bound GTP alters the activity of ion
    channels or enzymes such as
    adenylate cyclase, guanylate cyclase
    , phospholipase- C, which generates
    variety of second messengers like
    Activator is switched off when
    GTP is hydrolyzed to GDP by
    GTPase activity of the α subunit.
    G proteins can be either
    stimulatory or inhibitory.
    Stimulatory / inhibitory activity
    resides in the α subunit- Gs or Gi.
    Gs protein stimulates adenylate
    cyclase activity ↑ cAMP.
    Gi protein inhibits adenylate
    cyclase activity ↓ cAMP.
    cAMP
    cAMP as second messenger
    Protein kinase A
    Phosphorylation usually
    takes place on OH
    groups of serine,
    threonine/ tyrosine
    residues of the
    substrates.
    Glycogen synthase
    Phosphorylase kinase
    Hormone sensitive lipase
    Acetyl coA carboxylase
    Phenylalanine
    Adenylate cyclase
    Activated by –
    glucagon,
    epinephrine,
    calcitonin, ACTH,
    FSH,LH, hCG,
    ADH, GRH,PTH.
    Inhibited by-
    acetyl choline,
    angiotensin II &
    somatostatin.
    Phosphodiesterase
    Inhibited by caffiene and
    theophylline.
    Activated by Insulin.
    Clinical application- Cholera
    toxin
    ADP ribosylation of alpha subunit
    of Gs protein.
    cGMP as Second messenger
    ANF and Nitric oxide
    Involved in contractile function of
    smooth muscles, visual signal
    transduction (Rhodopsin) and
    maintenance of blood volume.
    cGMP as Second messenger
    ANF and Nitric oxide

    GTP
    Guanylate cyclase
    cGMP +PPi

    Protein kinase G

    Phosphorylates important proteins


    that regulate calcium dependent
    contraction or by modulating calcium
    influx-Smooth muscle relaxation and
    Cyclic GMP induces smooth muscle
    relaxation by multiple mechanisms
    including
    increased intracellular cGMP, which
    inhibits calcium entry into the cell,
    and decreases intracellular calcium
    concentration.
    activates K+ channels, which leads to
    hyperpolarization and relaxation.
    stimulates a cGMP-dependent protein
    kinase that activates
    myosin light chain phosphatase, the
    cGMP as Second
    messenger

    Drugs- Nitroglycerine used in Angina


    ANF- induces natriuresis , diuresis
    and a fall in blood pressure.
    NO- relaxes the smooth muscle
    tissues leading to vasodilatation
    and increased blood flow.
    Phototransduction- presence of light
    activates PDE which degrades cGMP
    to 5’GMP. This causes sodium
    channels to close, hyperpolarization
    of photoreceptor’s plasma
    membrane and ultimately to visual
    Hormones that use
    phosphatidyl inositol or
    calcium as 2nd messenger
    This system generates two
    intracellular messengers
    Inositol triphosphate and
    Diacylglycerol.
     PIP2 Phospholipase C IP3 and
    DAG

    IP3 Increases
    intracellular calcium stores.
    Calcium mediates its action by
    Calmodulin Ca2+ Ca2+-
    calmodulin
    complex

    protein kinase, myosin


    kinase

    PDH, Phosphorylase Kinase, Ca2+


    DAG
    DAG Ca2+ Protein kinase C

    Phosphorylates
    various proteins
    HMG CoA reductase, Tyrosine
    Hydroxylase.
    KINASE/PHOSPHATASE CASCADE PATHWAY

    Hormones of this group interact


    with receptors whose C terminal
    intracellular domains have tyrosine
    kinase activity.
    After binding of the hormone to
    extracellular domain, the
    intracellular domain of these
    receptors get autophosphorylated
    on tyrosine side chains.
    Initiates multistep phosphorylation
    KINASE/PHOSPHATASE CASCADE
    PATHWAY

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