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Receptors Functions and Signal
Transduction- L4- L5
Faisal I. Mohammed, MD, PhD
University of Jordan
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Tyrosine Kinase Receptors:
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 Receptors superfamilies:
Ionotropic receptors (ligand-gated channels)
Metabotropic receptors (G protein-coupled receptors)
Tyrosine Kinase
Almost all neurotransmitters discovered so far have more
than one kind of receptor -- called receptor subtypes.
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Epinephrine Can Act Through Two 2nd
Messenger Systems
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Free hormone
Blood capillary
1 Lipid-soluble
Transport
protein
hormone
diffuses into cell
2 Activated
Nucleus
Receptor
receptor-hormone
complex alters
gene expression
DNA
Cytosol
mRNA
3 Newly formed
mRNA directs
synthesis of
specific proteins
on ribosomes
Ribosome
New
protein
4 New proteins alter
Lipid-soluble
Hormones
cell's activity
Target cell
Hormones That Bind to Nuclear Receptor
Proteins
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
Lipophilic steroid and
thyroid hormones are
attached to plasma
carrier proteins.
 Hormones dissociate
from carrier proteins
to pass through lipid
component of the
target plasma
membrane.
Receptors for the
lipophilic hormones are
known as nuclear
hormone receptors.
Nuclear Hormone Receptors
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Steroid receptors are located in cytoplasm and in the
nucleus.
Function within cell to activate genetic transcription.
 Messenger RNA directs synthesis of specific
enzyme proteins that change metabolism.
Each nuclear hormone receptor has 2 regions:
 A ligand (hormone)-binding domain.
 DNA-binding domain.
Receptor must be activated by binding to hormone
before binding to specific region of DNA called HRE
(hormone responsive element).
 Located adjacent to gene that will be transcribed.
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Mechanisms of Steroid Hormone Action

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Cytoplasmic receptor
binds to steroid hormone.
Translocates to nucleus.
DNA-binding domain
binds to specific HRE of
the DNA.
Dimerization occurs.
 Process of 2 receptor
units coming together at
the 2 half-sites.
Stimulates transcription of
particular genes.
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Blood capillary
1 Binding of hormone (first messenger)
to its receptor activates G protein,
which activates adenylate cyclase
Water-soluble
hormone
Adenylate cyclase
Receptor
Second messenger
G protein
ATP
cAMP
2 Activated adenylate
cyclase converts
ATP to cAMP
Protein kinases
6 Phosphodiesterase
inactivates cAMP
3 cAMP serves as a
second messenger
to activate protein
kinases
Activated
protein
kinases
4 Activated protein
Protein
kinases
phosphorylate
cellular proteins
ATP
ADP
Water-soluble
Hormones
Protein— P
5 Millions of phosphorylated
proteins cause reactions that
produce physiological responses
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Target cell
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Hypophysiotropic Hormones
Hormone
Predominant
hypothalamic
localization
Structure
Actions on Anterior Pituitary
Thyrotropin-releasing
hormone (TRH)
Paraventricular
Peptide consisting of Stimulates secretion of TSH by
3 amino acids
thyrotropes; stimulates expression
of genes for  and ß subunits of TSH
thyrotropes; stimulates synthesis of
PRL by lactotropes
Gonadotropin-releasing
hormone (GnRH)
Arcuate
Single chain of 10
amino acids
Stimulates secretion of FSH and LH
by gonadotropes
Corticotropin-releasing
hormone (CRH)
Paraventricular
Single chain of 41
amino acids
Stimulates secretion of ACTH by
corticotropes; stimulates expression
of gene for POMC in corticotropes
Growth hormone-releasing
hormone (GHRH)
Arcuate
Single chain of 44
amino acids
Stimulates secretion of GH by
somatotropes; stimulates expression
of gene for GH in somatotropes
Single chain of 14
amino acids
Inhibits secretion of GH by
somatotropes
Dopamine
Inhibits biosynthesis and secretion
of PRL by lactotropes
Growth hormone-inhibiting Anterior
hormone (somatostatin) periventricular
Prolactin-inhibiting
hormone (PIH)
Arcuate
Mechanism of Thyroid Hormone Action
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
T4 passes into cytoplasm and is
converted to T3.
Receptor proteins located in
nucleus.
 T3 binds to ligand-binding
domain.
 Other half-site is vitamin A
derivative (9-cis-retinoic)
acid.


DNA-binding domain
can then bind to the halfsite of the HRE.
Two partners can bind to the
DNA to activate HRE.

Stimulate transcription
of genes.
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Cyclic Monophasphate (cAMP) Second Messenger
Mechanism
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Cell Membrane Phospholipid Second Messenger
System
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Tyrosine Kinase
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Tyrosine Kinase
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Insulin receptor consists of 2 units that dimerize
when they bind with insulin.
 Insulin binds to ligand–binding site on plasma
membrane, activating enzymatic site in the
cytoplasm.
Autophosphorylation occurs, increasing tyrosine
kinase activity.
Activates signaling molecules.
 Stimulate glycogen, fat and protein synthesis.
 Stimulate insertion of GLUT-4 carrier proteins.
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Tyrosine Kinase
(continued)
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The Insulin Receptor & Mechanisms
of Insulin Action
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Protein Hormones –
Mechanisms of Action
Adenylyl Cyclase
Mechanism
ACTH
LH
FSH
TSH
GHRH
Somatostatin
ADH (V2 receptor)
HCG
MSH
CRH
Calcitonin
PTH
Glucagon
Phospholipid
Mechanism
Guanylate Cyclase
Mechanism
GnRH
TRH
PTH
Angiotensin II
ADH (V1 receptor)
Oxytocin
ANP
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Tyrosine Kinase
Mechanism
Insulin
IGF-1
GH
Prolactin
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Steroid & Thyroid Hormones - Mechanism of
Action
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Determinants of Free Hormone Receptor
Binding
Carrier-bound
hormone
Endocrine
cell
Free
Hormone
Hormone
receptor
Hormone
degradation
Biological
effects
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Correlation of Plasma Half-Life & Metabolic Clearance
of Hormones with Degree of Protein Binding
Hormone
Protein
Plasma half-life
binding (%)
Metabolic clearance
(ml/minute)
Thyroid
Thyroxine
Triiodothyronine
99.97
99.7
6 days
1 day
Steroids
Cortisol
Testosterone
Aldosterone
94
89
15
100 min
85 min
25 min
140
860
1100
Proteins
Thyrotropin
Insulin
Antidiuretic hormone
little
little
little
50 min
8 min
8 min
50
800
600
0.7
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MCR = (mg/minute removed) / (mg/ml of plasma) = ml cleared/minute
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Circulating Transport Proteins
Principle Hormone
Transported
Transport Protein
Specific
Cortisol, aldosterone
Corticosteroid binding globulin
(CBG, transcortin)
Thyroxine binding globulin (TBG) Thyroxine, triiodothyronine
Testosterone, estrogen
Sex hormone-binding globulin
(SHBG)
Nonspecific
Albumin
Transthyretin (prealbumin)
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Most steroids, thyroxine,
triiodothyronine
Thyroxine, some steroids
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Feedback Mechanisms
Positive Feedback
Negative Feedback
+
+
Endocrine
cell
_
Target
cell
Endocrine
cell
Target
cell
+
Biological effects
Biological effects
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Steroid & Thyroid Hormones - Receptors
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Actions of Thyroid Hormones
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Insulin Action on Cells:
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Signaling molecule
(hormones)
Receptor of target cell
Signal
transduction
Intracellular molecule
(second messengers)
biological effect
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Third messengers:
Third messengers are the molecules which
transmit message from outside to inside of
nucleous or from inside to outside of nucleous,
also called DNA binding protein.
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Effect by
membrane
receptors
Extracellular
molecules
Effect by
intracellular
receptors
Signal
molecules
Intracellular
molecules
Proteins and peptides:
Hormones, cytokines
Amino acid derivatives:
Catecholamines
Fatty acid derivatives:
Prostaglandins
Steroid hormones,
Thyroxine, VD3
cAMP, cGMP, IP3, DG, Ca2+
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