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Chemistry of
Hormones
Definition
Organic substances produced in small
amounts by specific tissues
(endocrine glands) secreted into
blood stream to control the
metabolic & biological activities
in target cells
Chemical Messengers
Endocrine Glands
Secrete their product directly into
bloodstream
Known as ductless glands
The Players
Characteristics
of Hormone
Role of Hormones
Organ #1 Organ #2
Hormones are the e-mail messages of the body
The Bodys Long-Distance Regulators
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I have a receptor,
so we just click!
Hormones affect target cells with
specific receptors
Hormones have a specific
pattern and rate of secretion
Endocrine Rhythms:
0800 2000 0800
ACTH
0800 2000 0800
Cortisol
0800 2000 0800
TSH
0800 2000 0800
GH
0800 2000 0800
Testosterone
0800 2000 0800
LH
"It don't mean a thing if it ain't got that swing!"
Insect metamorphosis
Is regulated by hormones
Hormones are constantly
deactivated by the liver or cellular
metabolism and excreted by the
kidneys
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Hormones work in conjunction
with the nervous system
Hormones resemble enzymes
in three ways-
1. Act as catalyst
2. Needed in small amounts
3. Not used up in the reaction
Difference between Enzyme &
Hormone
Discharged in blood prior
to use
Synthesized at cellular
level where they perform
their function
All are not protein. Only
some are protein
All are protein
Produced in one organ &
perform action in other
(target organs)
Utilized at the site where
they are produced
Hormone Enzyme
Other Categories of Hormones
1. Paracrine hormones act
on adjacent cells from
where they are released
E.g. Prostaglandins & GF
(GF controls cell
proliferation)
2. Autocrine hormones act
on same cell where
produced E.g. IL-2
produced by T-cells are
responsible for stimulation
of their proliferation
Figure 6-2b, c: Long distance cell-to-cell communication
3. Neurotransmitters released by
nerve cells & usually act on adjacent
cells. Similar to hormones wrt
synthesis, transport & mechanism of
action
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Classification
1. Based on chemical nature
2. Based on mechanism of action
1. Based on chemical nature
1. Protein or peptide hormone
E.g. Insulin, ADH, Oxytocin, Glucagon,
etc.
2. Steroid hormone
E.g. Sex hormones, Glucocorticoids,
Mineralocorticoids etc.
3. Amino acid derivative
E.g. T3, T4, Epinephrine,
Norepinephrine etc.
2. Based on mechanism of
action
Based on location of receptors to which
they bind & signals used to mediate
their action
1. Group I Hormones bind to
intracellular receptors
2. Group II Hormones bind to cell
surface receptors & release second
messengers
Table 19.1
TRH
GRH,
GRIH
PRIH
GnRH
GnRH
CRH
Mechanism
of Action
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Receptor locations
Cytosolic or Nuclear
Lipophilic ligand enters
cell
Often activates gene
Slower response
Cell membrane
Lipophobic ligand can't
enter cell
Outer surface receptor
Fast response
Target cell receptors
Group I Hormones
Lipophilic & can pass across plasma
membrane
Derivatives of cholesterol e.g. estrogen,
androgen, glucocorticoids, calcitriol etc.
(except T
3
& T
4
)
Act thru intracellular receptor located in
cytosol or nucleus
Group I Hormones
Hormone + Intracellular Receptor
Hormone-Receptor Complex (HRC)
Binds specific region on DNA (HRE/ Hormone Responsive
Element)
Transcription
Translation
Biological function
Steroid Hormones: Action
Steroid hormone action
Hormone Action
Steroid, Thyroid
T-3
TBG
-receptors
Increased HR
T-3
T-3
R T-3
T-3
R
R
Group II Hormones
Hormones themselves are first
messengers
Hydrophilic
Transported in free form
Possess short half-lives
Bind to cell surface receptors
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Group II Hormones
Hormone + Cell Surface Receptor
Release second messengers
Perform biological function
Hormone Action
peptide and cathecolamines
TSH
R
effect
2nd
messenger
T-4
I
I I
I
TSH
TSH R
protein
Sub-divided into three groups-
1. Second messenger is cAMP ACTH,
FSH, LH, PTH, Glucagon & Calcitonin
2. Second messenger is PI/ Ca
2+
TRH,
Gastrin, GnRH etc.
3. Second messenger is unknown
GH, Insulin, Oxytocin, Prolactin etc.
Action of
cAMP
cAMP
Cyclic AMP is most common second
messenger
Hormones bind receptors, and membrane-
bound adenylyl cyclase is activated via the G
protein
Adenylyl cyclase catalyzes the conversion of
ATP to cAMP
cAMP activates protein kinases
Protein kinases catalyze the phosphorylation
of a specific protein, which triggers a chain of
reactions leading to the particular metabolic
effect of the hormone
Protein kinases are very specific in action
cAMP is rapidly inactivated and converted to
AMP
Synthesis & Degradation of
cAMP
Adenylate Cyclase System
Action of cAMP
Dephosphorylation of protein
Degradation of cAMP
ATP cAMP 5`AMP
Membrane-bound enzyme
Adenylate Cyclase
Phosphodiesterase
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G Proteins
G-protein linked receptors are
transmembrane proteins that loop 7 times
through the plasma membrane
Receptor activates G protein, which binds
GTP
When inactive, G protein is bound to GDP
G proteins interact with adenylyl cyclase,
which makes cAMP
G
s
stimulates adenylyl cyclase
G
i
inhibits adenylyl cyclase
When the hormone binds to a stimulatory
receptor, the G protein releases GDP and
binds to GTP
Binding of the G protein to GTP enables it to
activate adenylyl cyclase
Protein Kinases
Protein kinases
phosphorylate proteins
i.e. they add one or more
phosphates
cAMP is inactivated by
phosphodiesterases,
which quickly act to
downregulate its activity
GTP
GDP
GDP
GTP

4 ATP
4 cAMP
Cell response
AT
Protein
kinase
ADP
P
Inactive
protein
Active
protein
hormone
Adenylate cyclase
Signaling System
AC
R
S
Inhibitor
R
i


Action of
PI/ Ca
2+
IP
3
and
DAG
Phospholipid products can act
as second messengers
Phosphatidyl inositol 4,5
bisphosphate is split into
inositol trisphosphate (IP
3
)
and diacylglycerol (DAG)
IP
3
causes the release of Ca
++
from the ER
DAG goes on to activate
protein kinase C (PKC) along
with the Ca
++
- CaM complex
PKC in turn phosphorylates
protein that go on to generate
various cellular effects
Calcium Ions
Calcium ions can act as second
messengers
The non-stimulated cytoplasmic
calcium concentration is very low;
some stimulation events cause
transient elevation of intracellular
calcium
Calcium can bind proteins and
regulate cellular function as a result
One example of such calcium
protein binding is the calcium-
calmodulin (CaM) complex
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Ca
++
Based
Regulation
Calcium entry can
occur in response to a
G-protein stimulated
event
The calcium may bind
CaM and activate a
protein kinase that
may go on to regulate
other cellular events
Second Messenger
is Unknown
Tyrosine Kinase Receptors
Ligand
N
C
Cross
phosphorylation
Hormone Signal Amplification
Hormone signals can be amplified
A single hormone-receptor complex can
induce the production of many cAMP
molecules; this amplifies the strength of
the response
Conclusions
Hormones are essential for normal
growth, development, metabolism,
energy, reproduction etc.
Hormones are tightly regulated by
multiple systems
Both over and underproduction of
hormones leads to clinical disease
Pearls of Wisdom
If you think its over active try to suppress
If you think its under active try to
stimulate
Never get imaging before biochemical
diagnosis
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Finally
Hormones
You cant live without them but
You cant even live with them!