Endocrinology
Endocrinology is concerned with the
study of the biosynthesis, storage,
chemistry, and physiological function
of hormones and with the cells of the
endocrine glands and tissues that
secrete them.
Hormones
• Hormones are the chemical messengers
of the body. They are defined as organic
substances secreted into blood stream to
control the metabolic and biological
activities.
• These hormones are involved in
transmission of information from one
tissue to another and from cell to cell.
These substances are produced in small
amounts by various endocrine (ductless)
glands in the body.
They are delivered directly to the blood in •
minute quantities and are carried by the blood
to various target organs where these exert
physiological effect and control metabolic
activities. Thus frequently their site of action is
away from their origin. Hormones are required
in trace amounts and are highly specific in
their functions.
The deficiency of any hormones leads to a •
particular disease, which can be cured by
administration of that hormone.
The similarities and differences of
hormone with enzyme.
• Hormones act as body catalysts resembling
enzymes, like enzymes they are required in small
quantities, and they are not used up during the
reaction.
• While they are differ with enzymes:
• 1-They are usually produced in an organ other
than that in which they ultimately perform their
action.
• 2-They are usually secreted in blood prior to use.
• 3-Structurally, they are not always proteins.
Enzymes
Hormones
1-They are only proteins in nature and may have a
metallic group.
1-They are proteins, amino-acids, steroids etc.
2-Enzymes have vitamins and inorganic element are
prosthetic groups. Without which, they do not act.
2-They have no prosthetic groups.
3-Relatively large in size
3-Small in size.
4-Catalysts to enhance rate of reactions
4-Signal passers from one cell to other or between organs.
5-They stay as such after their function.
5-They are damage during the process and hence cannot be
reused
6-They function under strict conditions of temperature
and pH in body.
6-They are not limited by temperature or pH but controlled by
brain or external factors.
7-They are formed and also act at the site of action
7-They are formed and act at a distant site
8-They have limited but essential functions
8-They have diverse functions to control body growth,
reproduction and physiology
Endocrine action:- The hormone is distributed in blood and
binds to distant target cells.
Paracrine action:- The hormone acts locally by diffusing from
its source to target cells in the neighborhood.
Autocrine action:- The hormone acts on the same cell that
produced it.
Target tissue:- For a given hormone is a tissue
contains specific receptor proteins that bind the
hormone and initiate a cellular response
• Receptors :- Are specific molecules within the cell
membrane , cytoplasm or nucleus of the target cell
that are necessary for recognition and binding of extra
cellular messenger (hormone)
Target tissue must have two characters in responce
to the hormone
– 1-The tissue should recognize the hormone by a
receptor.
– 2-The tissue should have intracellular capacity of
translating the massage of the hormone to
biochemical event or reaction.
Regulation of target tissue activity.
The hormones regulate the activities of their
target tissues in two ways:1-By regulating the activities of already
present proteins in the cells, this takes place
rapidly within minutes.
2-By regulating the synthesis or
degradation of proteins, taking place more
slowly requiring hours or days.
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• Hormones as a signal
Hormonal signaling involves the following:
1-Biosynthesis of a particular hormone in a particular
tissue.
2-Storage and secretion of the hormone.
3-Transport of the hormone to the target cell(s).
4-Recognition of the hormone by an associated cell
membrane or intracellular receptor protein.
5-Relay and amplification of the received hormonal
signal via a signal transduction process: This then leads
to a cellular response. The reaction of the target cells
may then be recognized by the original hormoneproducing cells, leading to a down-regulation in hormone
production. This is an example of a homeostatic negative
feedback loop.
6-Degradation of the hormone.
Interactions with receptors
• Hormone-receptor complex concentrations
are effectively determined by three
factors:
• 1-The number of hormone molecules
available for complex formation.
• 2-The number of receptor molecules
available for complex formation.
• 3-The binding affinity between hormone
and receptor
Characteristics of Receptors
Classification according to the
mechanism of action
• There are 2 groups:• Group I :- includes H. that bind
the intracellular receptors
• Group II: - includes H. that bind
to cell surface receptors.
Mechanism of action
Group I (H.that bind to intracellular receptors)
Mechanism of action of group II (Hormone
that bind to cell surface receptor)
Clinical Significance of G-Protein
The factors that regulate hormone action
• Action of a hormone at a target organ
regulated by four factors: _
1-Rate of synthesis and secretion of hormone.
2-Specific transport systems in plasma.
3- Hormone-specific receptors in target cell
membrane which differ from tissue to Tissue.
4-Ultimate degradation of the hormone
usually by the liver or kidneys.
Hormonal Regulation
• The ability of a cell to respond to a hormone
depends on two properties of the receptor
molecule:
• 1- How many of them are on a particular
cell.
• 2- How well they bind the hormone.
• The first property is called the receptor
number, and the second is called the affinity
of the receptor for the hormone. The
biochemical responsiveness of a cell to a
hormone
Hormones Receptor Interaction
• Hormone + receptor  hormone – receptor
complex
• This complex usually undergoes
conformational changes resulting from
interaction with the hormonal ligand.
These changes allow for a subsequent
interaction with a transducing protein
(G-protein) in the membrane or for
activation to a new state in which active
domains become available on the
surface of the receptor.
Activation of Adenylate cyclase
• Adenylate cyclase is a membrane-bound enzyme
that is found in the plasma membranes of most
mammalian cells. The system works as follows:• Hormone binds to the membrane receptor protein
(R).
• This binding produce a conformational change
which allows the bound GDP to exchange for GTP.
As long as the site contains GTP, adenylate cyclase
will be activated.
• When GTP is hydrolysed by the GTP ase activity of
the guanine nucleotide binding protein leaving
GDP on the binding site, activation is reversed.
• The enzyme can only be activated by the addition
of hormone together with GTP or analogue of GTP.
Action of cAMP in cells.
• Kinase is a tetramer made up of two types of subunit: - two
regulatory and two catalytic subunits (C). Each R contains
two binding sites for cAMP .
• The liberated catalytic subunits ( C ) are able to
phosphorylate proteins to produce a cellular effect of
specific enzymes.
• The enzymes may be either activated or inhibited by
phosphorytation.
• cAMP is inactivated by phosphodiesterase, which catalyze
the conversion of cAMP to AMP.
• The activity of phosphodiesterase may also be regulated by
hormone.
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Adenylate cyclase
phosphodiestrase
AMP +  cAMP ------------------------ATP ------------------------- •
Pi
Phosphatidylinositol or Calcium Second
Messenger
• Certain hormone receptor interaction result in the activation
of the enzyme phospholipase C attached to the inside
projections of the receptors. The receptor binding and
activation of phospholipase C are coupled by a specific G –
protein
• Certain hormones enhance membrane permeability to Ca ²
influx, this is probably accomplished by:• Na +1 - Ca +² exchange mechanism.
• Ca +² – 2H ATP ase – dependent pump..
Calcium Calmodulin Second Messenger
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It is the calcium – dependent regulatory protein,
which is homologous to the muscle protein
troponin C in structure and function.
It has four Ca +² binding sites, and full occupancy of
these sites leads to a marked conformational
change.
This conformational change is presumably linked to
calmodulins ability to activate or inactivate
enzymes.
The hypothetical sequence of interactions between
Ca +², calmodulin and target enzyme as follows:•
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Calomdulin binds 2Ca +² at the high- affinity sites.
Conformational chang in calmodulin
Calmodulin / 2Ca +² complex binds to target
enzyme
Conformational change in enzyme.
Second change in calmodulin conformation
consequent upon change in enzyme conformation
increase in Ca +² affinity of site 3 and 4.
Association of 2 further Ca +².