2402 : Anatomy/Physiology
Dr. Chris Doumen
Lecture 1
The Endocrine System
Introduction
TextBook Readings
♦ Pages 594 through 605.
♦ Make use of the figures
in your textbook ; a
picture is worth a
thousand words !
♦ Work the Problems and
Questions at the end of
the Chapter
Together with the N.S., the endocrine
system coordinates functions of all
body systems
Nervous system :
• operates via electrical impulses
and neurotransmitters
• excites or inhibits neurons, muscles
and glands
• nerve impulses produce their
effect quite rapidly, within
millisecond
• the lingering effect of the N.S.
stimulus is very short
Endocrine System :
• releases messenger molecules
called hormones into the
bloodstream
• bloodstream transports this to
virtual all cells to see
• action of the messenger depends
on the presence of specific
receptors for these hormones
• Hormones act slower; over a period
of seconds to several hours
• Lingering effect of the Endocrine
system is longer lasting
Both systems use chemical messengers
to transmit signals between cells, the
intercellular messengers. These
messengers can only have an effect if
the target cell has a receptor for this
messenger.
In the nervous system, these receptors
are found on the post-synaptic
membranes.
In the endocrine system, these receptors
are proteins located on specific target
cells and can be found
• In the plasma membrane: used by
messengers that can not pass
directly through the membrane.
Membrane bound Receptors are
trans-membrane proteins
• Within the cell's nucleus ( used by
messengers that are lipid soluble and
can zip right though membranes)
Messengers can alter cellular activity by
decreasing or increasing the rate of
cellular processes. However, as
mentioned above, for a target cell to
respond, it must have receptors on that
the messenger can bind to. No receptors
... no response.
Paracrine factors versus Hormones
Collin County
Community
College District
•
Both chemicals enter the bloodstream.
•
Paracrine agents are usually low in concentration and only affect nearby cells
( influence their own tissue of origin).
•
Hormones are released by one cell/tissue group and affect cells in other
tissues.
These definitions sometimes become blurred as some paracrine agents act more
like hormones and some hormones act more like paracrine agents !
2402 : Anatomy/Physiology
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Cellular responses
The response eventually prompts the cell to turn on or turn off some cellular process.
Hormones can thus be viewed as molecular triggers. The binding of the hormone (ligand) to the
receptor initiates membrane events that are transduced internally into the cell, resulting in
some change within the cell. Studies have shown that the interplay between messenger and
receptor can take on different forms.
Cell specific receptors - cell specific events
• A specific messenger (e.g. hormone ) may come in contact with several types of cells
but only have an effect one type of cell. This indicates that only that type of cell has
the specific required receptor to bind this ligand. Only that cell will show a response
Common receptors - cell specific events
• Two cells may posses the same kind of receptor and bind the same kind of hormone but
produce a different result. This indicates that both hormone and receptor switch on an
event; the event is however cell specific. Thus something must be different at a point
beyond the receptor
Different receptors - same hormone
• A single cell may have different types of receptors that bind the same hormone. The
binding of the hormone results in a different effect, depending on the receptors to
which it binds to; once again indicating some different way things are handled after
binding to the receptor.
As will become evident later, the event that occurs within a cell is dependent on how the
receptor is connected to other specific membrane proteins and not on the hormone The hormone
(messenger ) just switches on the event. Think of a two similar looking switches ( receptors).
One turns on a fan, the other a light-bulb. It is not your finger ( the messenger) that
determines what event will occur; the wiring from the switch to the event ( let there be light
or let there be a breeze) determines the action. Your finger is just there to start the event.
Cut the wire to the fan and your finger becomes useless.
In the diagram on the right, a hormone is
produced by a certain secretory (endocrine) cell.
After traveling within the bloodstream the
hormone will only affect type A-cells because
these kind of cells have the membrane receptor
that binds this specific hormone. Cell types B
and C will have no response; they are virtually
“blind” to the existence of this circulating
hormone because they have no receptor for this
hormone.
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2401 : Anatomy/Physiology
The Endocrine System
The Endocrine system includes all cells and tissues which produce and secrete hormones or
paracrine agents that have an effect beyond their tissue of origin. (see Fig. 16-1)
Hormones are produced in the cells of Endocrine Glands. The product is released into the
extracellular space where it diffuses into a rich network of capillaries and lymph vessels.
The endocrine tissues are usually very small and scattered throughout the body.
The following endocrine glands make up the Majority of the Endocrine System with respect to the
hormones released
• Pituitary gland and Hypothalamus
• Pineal gland
• Thyroid and parathyroid glands
• Adrenal glands
In addition
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, several organs contain pockets of hormone producing tissues
Pancreas, Gonads
Kidneys, stomach, small intestine
Liver, heart
Hormone Chemistry
In principal, most hormones can be classified into 2 main categories. Different textbooks consider the
classes in slightly different ways. The categories below are as outlined in the textbook.
1.
Amino Acid Hormones
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Derivatives of the amino acids (thus relatively small hormones)
They include tyrosine derivatives
• Thyroid hormones ( see fig. 18-2)
• The catecholamines Epinephrine, norepinephrine and dopamine
Also includes melatonin and histamine
Peptide and protein hormones
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consist out of a small chain of amino acids (from 3 up) to small proteins
synthesized on ribosomes in rough E.R., packaged by Golgi and secreted via vesicles
many hormones go through stages of first being synthesized into a pre-pro-hormone form ,
becoming a pro -hormone and eventually the actual active hormone after cleavage by certain
enzymes.
Also includes the larger protein hormones with carbohydrate side chains (glycoprotein hormones
with over 200 AA’s)
2401 : Anatomy/Physiology
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2. Lipid derivative hormones
a. Steroid hormones
• derived from a cholesterol backbone ( see Fig. 2-15 and Table 16-3)
• synthesized on smooth E.R.
• differences are in side groups which results in a variety of different functions
• most steroid hormones are produced by the gonads (testosterone, estrogen) and the cortex
area of the adrenal glands (aldosterone, cortisol,…)
• since steroids are lipid soluble, they tend to diffuse out of the cell into the blood stream
the moment they are synthesized
We will return to steroid hormones and the adrenal glands later.
b. Eicosanoids
• lipid derivatives of arachidonic acid, a plasma
membrane lipid
• they function as important paracrine agents
• important examples are
o leukotrines : released by activated white
blood cells
o prostaglandins : coordinate local cellular
activities
Hormone transport in blood
Most peptides and the catecholamines are water soluble. They are transported by the fact that
they dissolve into the aqueous environment of the blood plasma
The steroid hormones and thyroid hormones are not water-soluble. Their transport depends on being
bound to specific plasma binding proteins (BP). Not 100% of a specific hormone binds to the binding
proteins, but there is an equilibrium between available free hormone and bound hormone, which in
part depends on the concentration of binding hormone, the concentration of free hormone and the
binding affinity of the binding protein for the free hormone.
Free Hormone + BP <====> Hormone-BP complex
Only the free hormone can diffuse through membranes and cause an effect. Thus the concentration
of free hormone is of physiological importance and not the total concentration of hormone ( free +
bound)
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2401 : Anatomy/Physiology
Hormone action and Signal Transduction
The binding of the hormone (chemical messenger) to the receptor results in an action by the
receptor. This is referred to as receptor activation.
The receptor then sets in motion a series of cellular events that can be quite diverse. This
combination between {signal - receptor - cellular events } is called a signal transduction pathway.
From our previous discussion, we can make a distinction between two general kinds of hormones.
• Those that are lipid soluble : these will zip right into the cell without the need for a
membrane bound receptor. The receptor for this messenger is located inside the cell
• Those that are lipid insoluble : these messengers need to bind to a plasma membrane receptor
before they can exert and effect.
The Receptors are linked to cellular response systems.
• Hydrophobic signals typically change gene expression, leading to slow but sustained responses.
• Hydrophilic signals typically activate rapid, short-lived responses that can be of drastic
impact
We will first look at the signal transduction of hydrophobic messengers/hormones.
Hormones and Intracellular Receptors
Most lipid-soluble messengers are steroid hormones, thyroid hormones, or steroid derivatives. They
are usually transported in the blood bound to a carrier protein ( increases their solubility in the
blood and makes transport easier).
They can diffuse into the cell (simple transmembrane diffusion) according to their concentration
gradient and don’t need specific transporters to enter. However they do need receptors to exert
their effect
• once inside, they bind to an intracellular receptor. This receptor can be in the cytosol but
most are already in the nucleus
• binding of the hormone dissociates a chaperone molecule from the receptor, turning the
receptor in an activated state
• the activated hormone-receptor complex allows binding of the receptor to a DNA associated
acceptor protein ( thus the hormone receptor complex becomes a transcription factor)
• this turns on the transcription, producing mRNA for a specific gene and thus eventually
produces a specific protein (enzyme, structural protein, ...)
• activation of the receptor occurs via a phosphorylation mechanisms
See Fig. 16-4 in your textbook
2401 : Anatomy/Physiology
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Hormone action at the cell membrane
Hormones and Chemical messengers that cannot diffuse right through the plasma membrane need to
interact first with a membrane receptor before the signal transduction pathway can be started
This chemical messenger is called the first messenger
They bind to external membrane receptors and exert their internal effects by the production
of intracellular second messengers
A second messenger usually activates other pathways within the cell
Sometimes it results in the production of a third messenger , which in turn activates other
processes.
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Most such receptors interact with G-proteins to exert their effects. (see also Fig. 3-16)
Largest known group of plasma membrane
receptors
Receptor is a transmembrane protein
Bound to this receptor is a heterotrimeric
( contains 3 different subunits) protein
complex known as G-proteins
The G-proteins are located on the
cytosolic side but reside in the membrane
o The G - protein contains 3
subunits
o α subunit binds GTP and has and
has GTPase activity
o a tight complex of β and γ which
anchors the G protein to the
membrane
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Example of a muscarinic receptor that
interacts with a potassium channel via Gproteins.
When the receptor is not activated by binding of a hormone ( the first messenger) , the 3 G-protein
subunits cling together and are attached to the receptor. GDP is bound to the alpha subunit
Binding of hormone to the receptor, causes a conformational change in the receptor such that the
cytoplasmic part of the receptor binds to the alpha subunit of the G-protein complex
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This binding allows the alpha subunit to release GDP and bind GTP
The binding of GTP causes conformational changes in the α subunit such that it dissociates
from the receptor and from the beta-gamma subunits
It also promotes the dissociation of the hormone from the receptor
The α subunit can now link up with a membrane bound enzyme; activation of this enzyme will
produce the intracellular second messenger.
We will emphasize two examples that generate different kinds of intracellular messengers ( the
second messengers) .