ERD Biochemistry Lecture 1

Hormones
Intended learning outcomes (ILOs):
By the end of this lecture the student will be able to :

A1: Define hormones and point out endocrine glands.
A2. Describe mode of action of hormones.
A3: Point out classification and groups of hormones.
Definition
A hormone is a chemical messenger secreted in small
amounts by one type of tissue (called endocrine glands) and
carried directly by the blood to act in another tissue (called
target tissue) elsewhere in the body.
Endocrine glands have no ducts. they include:
- Hypothalamus , Pituitary, Thyroid , Islets of langerhans
, Parathyroid , Adrenals, Ovaries and testis.
Classification of hormones:
Hormones can be classified according to:
A-According to their chemical composition:
1- Amino acid derivatives: these include thyroid hormones
( T3 & T4) from tyrosine amino acid , also epinephrine and
norepinephrine from tyrosine and melatonin from
tryptophan amino acid .
2- Protein hormones: for example insulin, parathyroid and
growth hormone.
3- Steroid hormones: These include adrenocortical and sex
hormones.
B-According to location of receptor and nature of signal that
mediate hormone action within the cell:
Hormones are classified into 2 groups: I and II.
Group I hormones Group II hormones
1- Lipophilic, readily traverses the 1- Hydrophilic, (water soluble), can not
plasma membrane. penetrate plasma membrane.
2- After secretion, they bind to 2- do not bind to transport proteins.
transport proteins.
3- They bind to intracellular receptors 3- These bind to cell surface receptors.
(in cytosol or nucleus).
4- The intracellular messenger is the 4- Communicate with the intracellular
hormone - receptor complex. metabolic processes through
intermediary molecules called second
messenger.
5- Examples: steroid, thyroid 5- Examples: protein hormones and

hormones and calcitriol. catecholamines.
Mechanism of hormone action
A- Mechanism of action of group I hormones
✓ This group includes steroid hormones, T3 and T4 and
calcitriol.
✓ Group I hormones are lipophilic molecules that diffuse
through the plasma membrane of all cells.
✓ They bind to receptors present either in the cytoplasm or
nucleus of target cells. The hormone-receptor complex
then binds to specific region of DNA and activates or
inactivates specific genes, resulting in changes in the
amounts of specific proteins, which influence the
metabolic processes.
✓ Hormone -receptor element is a region in DNA that binds
hormone-receptor complex more avidly than other
regions of DNA.
1- Intracellular receptor:
Mechanism of action of group II hormones
➢ Group II hormones constitute the largest number of
hormones, which are water-soluble and initiate their
response by binding to receptors located on the
plasma membrane.
➢ These hormones communicate with intracellular
metabolic processes through second messengers,
which are generated as a consequence of ligand -
receptor interaction.
➢ The second messenger may be one of the following:
1- Cyclic adenosine monophosphate ( cAMP).
2-Cyclic guanosine monophosphate (cGMP)
3- Calcium and phosphoinositides.
4- Protein- kinase cascade as in mechanism of insulin
action .
1- Cyclic adenosine monophosphate (cAMP)
1- cAMP is derived from ATP by the action of the
enzyme adenylate cyclase, which is located on the
inner surface of the plasma membrane.
2- The interaction of the hormone with its receptor
results in the activation or inactivation of the adenyl
cyclase. This process is mediated by GTP- dependent
regulatory proteins (G proteins).
Gs ( stimulatory) and Gi ( inhibitory).
4- Hormones that stimulate adenylate cyclase include ACTH,
ADH, FSH, glucagon, LH, MSH, PTH and TSH.
5- Hormones that inhibit adenylate cyclase include:
acetylcholine, angiotensin II and stomatostatin.
6- The activated adenylate cyclase catalyzes formation of cAMP
from ATP.
7- cAMP binds to a protein kinase which consists of 2 regulatory
subunits (R) and 2 catalytic subunits (C). The binding of cAMP by R
dissociates R from C leading to the activation of C.
8- The active protein kinase catalyzes phosphorylation of a protein,
which exerts physiologic effects.
9-The actions caused by hormones that increase cAMP
concentration can be terminated by one of the following ways:
A- Hydrolysis of cAMP by phosphodiesterases.
B- Phosphoprotein phosphatases which cause dephosphorylation
of phosphoproteins.
2- Cyclic guanosine monophosphate (c
GMP)
Cyclic GMP is formed from GTP by the
action of the enzyme guanylate cyclase
cGMP activates cGMP-dependent protein
kinase which in turn phosphorylates a
number of smooth muscle proteins,
including myosin light chain cause
vasodilation and smooth muscle relaxation.
Example of hormones act through cGMP as a second messenger:

Atrial natruritic factor (ANF), and nitric oxide, These compounds are
vasodilators.
Calcium and Phosphoinositides
✓ The calcium or phosphoinositides are second messengers for
a number of hormones including: Oxytocin, Gonadotropin -
releasing hormone (GnRH) and Vasopressin.
✓ These hormones enhance membrane permeability to Ca2+
and thereby increase Ca2+ influx. Calcium binds to a
regulatory protein called calmodulin which has 4 Ca2+-binding
sites. When all these sites are occupied by Ca2+, marked
conformational change of calmodulin occurs, leading to
activation or inactivation of certain enzymes as Adenylcyclase
, Pyruvate kinase, Glycogen synthase and Guanylate cyclase.
✓ Phosphoinositide metabolism
affects Ca2+- dependent
hormone action.
The binding of the hormone
e.g. acetylcholine, antidiuretic
hormone to their cell surface
receptors activates the
enzyme phospholipase C. This
enzyme catalyzes the
hydrolysis of
phosphatidylinositol 4,5
bisphosphate to inositol
triphosphate and 1,2
diacylglycerol
✓ The diacylglycerol activates protein kinase, which
phosphorylates proteins whereas inositol triphosphate
releases calcium from intracellular storage sites such
as the sarcoplasmic reticulum and mitochondria.
References
· Textbooks of Medical Biochemistry, 7th edition by Chatterjea
MN. and Shinde R.
JAYPEE BROTHERS. New Delhi, India, 2007.
· Text book of Biochemistry with Clinical Correlations 5th Ed,
Devlin TM Ed.Wiley -Liss
New York 2002
Harper's Illustrated Biochemistry: 28th edition by Murray RK,
Granner DK, Mayes PA,
Rodwell VW, McGraw-Hill companies New York, 2009.
Lippincott's Reviews of Biochemistry, 4th edition by Champe PC,
Harvey RA, Ferrier DR,
Lippincott William & Wilkins London, 2008.

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Hormones

Intended learning outcomes (ILOs):

By the end of this lecture the student will be able to :

5- Examples: steroid, thyroid 5- Examples: protein hormones and

Example of hormones act through cGMP as a second messenger:

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