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SUDAN INTERNATIONAL UNIVERSITY

FACULTY OF MEDICINE

HORMONE SIGNAL
TRNSDUCTION
Tutorial no 1

Nagi Moh, Elfatih


Definitions
Hormones are chemical messengers secreted
by specialized cells (glands) to coordinate
metabolic activity of different cells in
multicellular organisms
Receptors are protein molecule that receives
and responds to a hormones, or other
substance
Cell surface receptor, a receptor on the
outer surface of a cell membrane
Nuclear receptor, a receptor found inside
the cell
Functions of hormones
coordinate metabolic activity of different
cells in multicellular organisms
Cell and tissue growth
Regulation of heart rate, blood pressure,
kidney function, motility of the GIT,
secretion of digestive enzymes and of other
hormones,
Regulation of lactation
Regulation of the activity of the reproductive
systems.
Classification of
hormones
According to chemistry
According to the distance between the
secreting and target cells
According to the secreting glands
According to the type of receptors
According to chemistry
Peptide hormones and proteins
Amino acids derived hormones
Steroid hormones
Eicosanoids
According to the
distance between the
secreting and target
cells Autocrine
Paracrine
Endocrine
According to the
secreting glands
According to the the
location of specific cellular
receptor hormones
Group I hormones interact with an
intra cellular receptor
Group II hormones with membrane
bound receptors
Hormonal signal
transduction
External or internal stimuli
General adaptive response to stimuli
Hormones are released
Target tissue
Hormones binds to specific receptors on/in
target tissues
Hormone receptor interaction
Generation of intracellular signal
Hormonal signal
transduction
The response to intracellular signal that can
either regulation the activity of a select set of
genes, or affection the activity of specific
proteins ( enzymes and transporter or
channel proteins).
The final outcome of the signal result in
protein synthesis, replication and cell
growth.
Hormonal signal
transduction
Other signaling molecules using the same
mechanisms include; cytokines, growth
factors, metabolites
Hormonal signal
transduction
Group I and Group II
Hormones
According to the location of specific cellular
receptor hormones are classified into two
groups:
1) Group I interact with an intra cellular
receptor
2) Group II with membrane bound receptors
Group I and Group II
Hormones
Group I and Group II
Hormones
Group I
Hormones
Group I hormones
(lipophilic hormones)
(hormones with intra-cellular receptors)
Group I hormones includes:
1. Steroid hormones and vit D
2. Thyroid hormones
3. Retinoic acid
group I hormones diffuse through the plasma
membrane to encounter intracellular receptors.
The receptor can be located in the cytosol or
the nucleus.
group I hormones have delayed
response ( hours to days )

group I hormones modulate the rate of


gene transcription.
Regulation of gene
transcription by
hormones
There are two types of gene:
Regulated genes
a) Positive regulation (inducer, enhancer or
positive effecter). Result in increased
expression of genetic information.
b) Negative regulation (repressor, suppresser
or negative effecter). These result in
diminished expression of genetic
information.
Housekeeping genes (un regulated):
constitutively expressed
Positive regulated genes
Steroid
hormones
mechanism of
action
1. Glucocorticoids
diffuse across the
plasma membrane
and encounter their
receptors in the
cytosol.
2. Binding of
Glucocorticoids to
their receptor in the
cytosol results in
release of heat shock
protein from the
receptor
3. then the complex is
transferred to the
nucleus . the receptor
also contains nuclear
localization sequences
assist in the transfer
from the cytosol to the
nucleus.
4.In the nucleus
the complex binds
with high affinity
to DNA sequence
(HRE).
The DNA-bound, hormone receptor complex
serves as a high affinity binding site for one
or more coactivator proteins
This results in accelerated gene transcription.

HRE HRE
HRE
Hormone receptor complex

accelerated gene transcription


Hormone response
element (HRE)
short sequence of DNA, within the promoter
of a gene. that is able to bind a specific
hormone receptor complex and therefore
regulate transcription.
Thyroid
hormones
mechanism of
action
1. The thyroid hormones
and retinoids diffuse
across the plasma
membrane and reach the
nucleus
The receptor for these is
already bound to
Hormone response
elements in DNA .
The DNA bound receptor
in the absence of the
hormone is bound to co-
repressor protein and
inhibit transcription.
binding of the hormone to
receptor lead to releases
the corepressor , and the
receptor-hormone
complex then binds to
coactivators resulting in
activation of gene
transcription.
Comparison
between
steroid and
thyroid
hormones
Thyroid hormone

Steroid hormone
Case senario
A 39-year-old female presents to the clinic for a routine health
check. The patient reports she is feeling nervous and anxious
all the time with frequent palpitations. On further questioning
she reports having diarrhea, has been losing weight and
frequently feels warm while others are cold or comfortable.
She denies any history of depression or anxiety disorder and is
not taking any medications.
On examination, her heart rate is 110 beats/min. She has a
slight tremor and has increased reflexes in all extremities. A
non tender thyroid enlargement is appreciated in the thyroid
region
Questions:
Define this terms:
Hormone.
Receptor.

Write about classification of hormones ? give examples

What we mean by the term (hormone signaling process)?

What is the most likely diagnosis?

What is the biochemical mechanism for this disorder?


1. Hormones that bind intracellular
receptors :
a. Also known as group II hormones
b. Water soluble hormones
c. Include insulin and glucagon
d. Usually regulate gene expression
e. All of the above is correct
2. Characteristic features of
receptors for steroid hormones
include
a. They can bind to heat shock protein
b. They are bound to DNA with out
ligand binding
c. They recruit co repressor molecules
d. Act rapidly when bind to the
hormone
e. None of the above
3. Hormones:
a. coordinate activities of different cell in
mammals.
b. action is mediated by binding to specific
receptor.
c. may act via stimulation of gene expression.
d. control tissue proliferation and differentiation.
e. All of the above is correct
4. Autocrine molecules
a. Act on cells far away from their
secreting cell
b. Act on cells near their secreting cell
c. Act on their secreting cell
d. Include thyroid hormones
e. All of the above is true
Thank You

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