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Mechanisms of hormone actions

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Title: Mechanisms of hormone actions


1
Mechanisms of hormone actions
  • Endocrine 412

2
Objectives
  • Defining hormones and their classifications.
  • Listing the general characteristics of hormones.
  • Identifying factors determining the response of
    target cells to hormones.
  • Describing the different mechanisms of action of
    hormones.
  • Listing hormones that bind to cell surface
    receptors.
  • Listing hormones that bind to intracellular
    receptors.

3
General characteristics of hormones
  • Hormones
  • are molecules that are produced by special cells
    (not by all cells of the body)
  • are secreted directly to blood (with no ducts)
  • are available in very low concentrations in blood
  • are transported in blood to work in distant sites
  • have systemic actions
  • have specific receptors (either intra- or
    extra-cellular ) in target tissues
  • have different special mechanisms of actions

4
Receptors of hormones
  • Hormones are present in very low concentrations
    in extracellular fluids (e.g. blood)
  • In order to initiate their biologic effects,
    target cells must recognize hormones by binding
    to specific receptors
  • A target cell is defined by its ability to bind
    selectively a given hormone via a receptor
  • Receptors have at least 2 DOMAINS
  • 1- Recognition domain binds to the
    hormone
  • 2- Coupling domain couples hormone
    recognition to some intracellular function by
  • generating a signal
  • Generally, COUPLING occurs by two ways
  • 1- Polypeptide hormones, protein hormones
    catecholamines binding of hormones to
  • plasma membrane receptors (extracellular
    receptors).
  • 2- Steroid thyroid hormones interact with
    intracellular receptors, form complexes that
  • generates a signal.

5
The concentration of hormone as seen by target
cells is determined by three factors
  • 1-Rate of production
  • Synthesis and secretion of hormones are the
    most highly regulated aspect of
  • endocrine control. Such control is mediated by
    positive and negative feedback circuits

6
The concentration of hormone as seen by target
cells is determined by three factors (cont.)
  • 2-Rate of delivery
  • An example of this effect is blood flow to a
    target organ or group of target cells
  • high blood flow delivers more hormone than low
    blood flow.
  • 3-Rate of degradation and elimination
  • Hormones, like all biomolecules, have
    characteristic rates of decay, and are
  • metabolized and excreted from the body
    through several routes.
  • Hormones are cleared by
  • 1- Metabolic destruction by tissues
  • 2- Binding with tissues
  • 3- Excretion by the liver into bile
  • 4- Excretion by the kidney into urine
  • 5- Clearance of protein bound hormones is slower
    than clearance of peptide hormones

7
Classifications of hormones
  • Hormones are classified according to
  • 1- Chemical composition (protein or others)
  • 2- Solubility (hydrophilic or lipophilic)
  • 3- Location of receptors (intra- or
    extra-cellular)
  • 4- Nature of signal used to mediate hormone
    action within cells
  • According to their classifications, hormones are
    classified into
  • Group I Group II (according to mechanism of
    action)

8
Classification of hormones according to
mechanism of actionGroup I
  • Hormones that bind to intracellular receptors
    (cytosolic or nucleus)
  • 1- Solubility lipophilic (to pass cell membrane
    which is mainly lipid)
  • 2- Chemical composition
  • Derived from cholesterol (except thyroid
    hormones retinoic acid)
  • 3- Transport in blood
  • Associate with transport proteins (to
    tackle solubility problem)
  • Long plasma half-life
  • 4-Mechanism of action
  • 1- Free hormone traverses plasma membrane
    of cells binds to receptor in cytosol or
    nucleus of target cells.
  • 2- Hormone-receptor complex binds to
    specific region in DNA of gene (hormone-response
    element, HRE)
  • 3- Binding causes activation or
    inactivation of specific gene(s) transcription
    (production of mRNA)
  • 4- Accordingly, amount of protein synthesis
    (production) is changed (protein may be enzymes
    of metabolic react.)
  • 5- Accordingly, certain metabolic
    processes are affected.

9
Example of Group I hormones Steroid hormones
via cytoplasmic receptors
10
Example of Group I hormones Retinoic acid
(active product of vitamin A) via nuclear
receptors
11
List of Group I hormones
  • Thyroid hormones
  • Steroid hormones
  • Glucocorticoids (e.g.
    cortisol hormone)
  • Mineralocorticoids
    (e.g. aldesterone)
  • Androgens (e.g.
    testosterone hormone)
  • Estrogens
  • Progestins (e.g.
    progesterone hormone)
  • Retinoic acid (active metabolite of vitamin A)
  • Calcitriol (1, 25 DHCC, active metabolite of
    vitamin D)

12
Classification of hormones according to
mechanism of actionGroup II
  • Hormones that bind to plasma membrane
    (extra-cellular) receptors
  • 1- Solubility hydrophilic
  • 2- Chemical composition
  • Polypeptides, proteins, glycoproteins
    catecholamines
  • 3- Transport in blood No transport protein-
    short plasma half-life
  • 4-Mechanism of action
  • Hormone binds to plasma membrane receptor
  • Hormone -receptor interaction leads to
    generation of second messenger intracellularly
    that communicates (couples) hormones binding
    with intracellular metabolic processes
  • Second messengers
  • 1- cyclic AMP (cAMP)
  • 2- cyclic GMP (cGMP)
  • 3- Calcium or phosphaitdyl inosiltol (or both)
  • 4- Kinase cascade

13
Second Messenger cAMP
14
List of Group II hormones
  • 1- Second messenger is cAMP
  • a2 b adrenergic Catecholamines
  • Adrenocorticotropic Hormone (ACTH)
  • Angiotensin II
  • Antidiuretic Hormone (ADH)
  • Calcitonin
  • Human Chorionic Gonadotropins (hCG)
  • Corticotropin-releasing hormone (CRH)
  • Follicle Stimulating Hormone (FSH)
  • Leutinizing Hormone (LH)
  • Glucagon
  • Ipotropin (LPH)
  • MSH (Melanocyte Stimulating Hormone)
  • Parathyroid Hormone (PTH)
  • Somatostatin
  • Thyroid Stimulating Hormone (TSH)

15
List of Group II hormones
  • 1- Second messenger is cGMP
  • Atrial natriuretic peptide (ANP)
  • Nitric Oxide (NO)
  • There are two isoforms of guanylate cyclase
    involved in production of cGMP
  • A membrane-bound guanylate cyclase ( for ANP
    bacterial endotoxin)
  • A cytosolic guanylate cyclase (for NO)

16
Second messenger cGMPAtrial Natriuretic Peptide
17
NO signaling in physiology
Nitric Oxide Synthase NO Binds to heme moiety of
guanylate cyclase Conformational change of the
enzyme Increased activity (production of
cGMP) Modulation of activity of other proteins
(protein kinases, phospho-diesterases, ion
channels) Physiological response (relaxation of
smooth muscles, inhibition of platelet
aggregation, etc.)
O2-
ONOO-
18
Second Messenger Phosphatidyl inositol calcium
19
List of Group II hormones
  • Second messenger is phosphatidyl inositol or
    calcium (or both together)
  • Acetylcholine
  • a1 adrenergic catecholamines
  • Angiotensin II
  • Antideuretic Hormone (ADH)
  • Cholecystokinin
  • Gastrin
  • Gonadotropin Releasing Hormone (GnRH)
  • Oxytocin
  • Platelet Derived Growth Factor (PDGF)
  • Substance P
  • Thyrotropin Releasing Hormone (TRH)

20
Second Messenger Kinase cascade (for
insulin hormone)
21
List of Group II hormones
  • Second messenger is kinase cascade
  • Chorionic somatomammotropin (CS)
  • Epidermal Growth factor (EGF)
  • Erythropoeitin (EPO)
  • Antideuretic Hormone (ADH)
  • Fibroblast Growth Factors (FGF)
  • Growth Hormone (GH)
  • Insulin
  • Insulin-like Growth factors (IGF-I IGF-II)
  • Nerve Growth Factor (NGF)
  • Platelet Derived Growth Factor (PDGF)
  • Prolactin (PRL)
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