Download Introduction to Endocrinology

Introduction to the Endocrine System
General Features and Definitions
Types of Hormones
Functions of the Endocrine System
Components of the Endocrine System
Chemical Structure of Hormones
Homeostasis
Endocrine vs. Nervous Systems
Control of Endocrine Activity
Regulation of Hormone Secretion
Transport and Distribution of Hormones
Mechanism of Hormone Action
Regulation of Hormone Receptors
General Features of the Endocrine System
1. Endocrine glands are ductless
2. Endocrine glands have a rich supply of blood.
3. Hormones, produced by the endocrine glands are
secreted into the bloodstream.
4. Hormones travel in the blood to target cells close
by or far away from point of secretion.
5. Hormones receptors are specific binding sites on
the target cell.
Important Definitions:
Endocrine System
• Endocrine--endo means within. This is a
system which controls body function through
hormones.
• Endocrine System is composed of a number of
glands.
• Glands are specialized tissues that produce a
hormone or product.
Important Definitions
• What are hormones?
Hormones are organic chemical messengers produced and
secreted by endocrine cells into the bloodstream. Hormones
regulate, integrate and control a wide range of physiologic
functions.
Silverthorn, Human Physiology, 3rd
edition Figure 6-1&2
Important Definitions
• What are endocrine glands?
Endocrine glands are ductless glands comprised of
endocrine cells. This means that these glands do not
have ducts that lead to the outside of the body. For
example, sweat glands are NOT endocrine glands
(they are instead exocrine glands) because sweat
glands have ducts that lead to the outside surface of
your skin (that’s how the sweat gets out). The fact
that endocrine glands are ductless means that these
glands secrete hormones directly into the blood
stream (instead of to the outside of your body).
Important Definitions
• What are target cells?
Target cells refer to cells that contain specific receptors (binding
sites) for a particular hormone. Once a hormone binds to
receptors on a target cell, a series of cellular events unfold
that eventually impact gene expression and protein synthesis.
Silverthorn, Human Physiology, 3rd
edition Figure 6-1&2
Important Definitions
• What are hormone receptors?
Hormone receptors are binding sites on the target cell (either on
the surface or in the cytoplasm or nucleus of the target cell)
that are activated only when specific hormones bind to them.
If a hormone does not/cannot bind to it’s receptor, then no
physiologic effect results.
See next slide for a picture of a hormone bound to its receptor
Growth hormone regulates cell growth by
binding to growth hormone receptors on target
cells.
Types of Hormones
Steroid Hormones
• These are all derived from
cholesterol.
• Examples: testosterone,
estrogen, progesterone,
mineralicoids,
glucocorticoids.
• Steroids can cross the
plasma membrane!
Other kinds of lipids.
Protein Hormones
• These are made of
amino acids.
• Examples: Insulin,
hypothalmus-signaling
hormones.
• Protein hormones
cannot cross the plasma
membrane!
Chemical Structure of Hormones
•
•
•
•
Two general classes of hormones: water soluble
and lipid soluble.
Water soluble (polar): proteins, glycoproteins,
polypeptides, amino acid derivatives.
Lipid soluble (nonpolar): steroids, amino acid
derivatives, fatty acids.
Different classes have different mechanisms of
action, different modes of transport through the
body, and differing stability in the circulation.
Examples of Water Soluble Hormones
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•
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Proteins: growth hormone, prolactin, insulin
Glycoproteins: follicle-stimulating hormone (FSH),
luteinizing hormone (LH) , thyroid-stimulating
hormone (TSH)
Polypeptides: arginine vasopressin, oxytocin,
somatostatin
Amino acid derivatives:epinephrine, melatonin
Examples of Lipid-Soluble Hormones
•
Steroids: estrogen, progesterone, testosterone,
glucocorticoids, mineralocorticoids
•
Amino acid derivatives: Thyroid hormones (T3, T4)
•
Fatty acids: prostaglandins, thromboxanes
Classes of Hormones
• Steroids vs. Peptide Hormones
Hormones fall into 2 general classes based on
their molecular structure and synthesis.
• All steroid hormones are made initially from
the precursor (precursor = first step in
biosynthetic pathway) cholesterol.
See next slide for a diagram of the biosynthetic pathway of steroid hormones
from cholesterol.
Steroid Hormones
• Steroid hormones are produced by the gonads
and adrenal cortex.
• Thyroid hormones are not steroids, but will be
categorized with steroids for simplicity.
• Steroid hormones are made from cholesterol
in the smooth endoplasmic reticulum and
mitochondria of endocrine cells.
Steroid Hormones
• Steroid hormones cannot be stored in vesicles
in the endocrine cells that produce them. As
soon as steroid hormones are produced, they
diffuse out of the endocrine cell and enter the
bloodstream.
• Steroid hormones are lipid soluble and their
receptors are located inside their target cell.
Peptide Hormones
• Peptide hormones are comprised of chains on
amino acids.
• Like most proteins, peptide hormones are
synthesized on ribosomes of the (rough)
endoplasmic reticulum of endocrine cells.
• Peptide hormones can be stored in vesicles in
endocrine cells until they are needed at some
later point.
Peptide Hormones
• Peptide hormones do not readily pass through
cell membranes (lipid bilayers) and they are
referred to as water soluble.
• Receptors for peptide hormones are found on
the cell surface of their target cells.
Some General Actions of Hormones
• Hormones cause cells to change.
• Hormones can result in changes in gene
expression (DNA-RNA-Protein).
• Hormones can result in enzyme cascades
which control our metabolism.
• Hormones drive our reproductive systems.
Some Specific Actions of Hormones
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Fetal development and differentiation
Cell growth and cancer
Metabolism
Cardiovascular function
Renal function
Skeletal function
Reproductive function
Immune function
Central nervous system function
Homeostasis
• Definition: the maintenance of a constant
environment (internal).
• Parameters regulated: Temperature, osmolarity,
pH, nutrient levels, hormone levels, etc.
• Homeostasis is critical for cell viability and proper
functioning.
• Loss of homeostasis results in disease/death.
• Homeostasis is maintained by feedback
mechanisms (primarily negative feedback).
Another Example: Regulation of LH Release in
the Male
• LH increases production of testosterone from the
testis.
• Testosterone feeds back upon the pituitary to inhibit
LH release.
pituitary
(-)
LH
testis
testosterone
Another Example of Homeotasis:
Regulation of Blood pH Levels
Blood
pH
7.5
7.3
Feedback control
• Negative feedback is most common: for example, LH
from pituitary stimulates the testis to produce
testosterone which in turn feeds back and inhibits LH
secretion
• Positive feedback is less common: examples include
LH stimulation of estrogen which stimulates LH surge
at ovulation
Negative feedback effects of cortisol
Substrate-hormone control
• Glucose and insulin: as glucose increases it
stimulates the pancreas to secrete insulin
Feedback control of insulin by
glucose concentrations
Endocrine overview
• Hormones are released by glands.
• Hormones are released by feedback.
• Our body works to carefully regulate hormone
levels.
• Negative feedback usually controls hormone
secretion.
Homeostasis and Controls
• Successful
compensation
– Homeostasis
reestablished
• Failure to compensate
– Pathophysiology
• Illness
• Death
Figure 1-5: Homeostasis
Feedback Loops
Figure 6-26: Negative and positive feedback
Negative Feedback Controls:
Long & Short Loop Reflexes
Endocrine Reflex Pathways: Overview
Pathologies: Over or Under Production
Pathologies: Due to Receptors
Endocrine vs. Nervous System
• Major communication systems in the body
• Integrate stimuli and responses to changes in
external and internal environment
• Both are crucial to coordinated functions of
highly differentiated cells, tissues and organs
• Unlike the nervous system, the endocrine
system is anatomically discontinuous.
Nervous system
•The nervous system exerts
point-to-point control through
nerves, similar to sending
messages by conventional
telephone. Nervous control is
electrical in nature and fast.
Functions of the Endocrine System
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Contributes to and interacts with the control and
integration functions of the nervous system
Important in the maintenance of homeostasis (set
points), usually through negative feedback
Occasionally involved in processes with controlled
movement away from set point (positive feedback)
Why Two Systems? Comparison of Nervous
and Endocrine Systems
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The nervous system responds to changes in the
environment quickly, the endocrine system more gradually.
The effects of nervous system action are short-lived, while
the effects of endocrine changes persist longer.
The nervous signal (neurotransmitter) is highly localized (at
the synapse), the endocrine signal (hormone secretion) is
systemic.
The magnitude of nervous system effects are dependent
upon the frequency of action potentials (frequency
modulated); the magnitude of endocrine effects are
dependent upon the amount of hormone released
(amplitude modulated).
Hormones travel via the
bloodstream to target cells
•The endocrine system
broadcasts its hormonal messages
to essentially all cells by secretion
into blood and extracellular fluid.
Like a radio broadcast, it requires a
receiver to get the message - in the
case of endocrine messages, cells
must bear a receptor for the
hormone being broadcast in order
to respond.
A cell is a target because is has a specific
receptor for the hormone
Most hormones circulate in blood, coming into contact with essentially all
cells. However, a given hormone usually affects only a limited number of
cells, which are called target cells. A target cell responds to a hormone
because it bears receptors for the hormone.
Principal functions of the endocrine
system
• Maintenance of the internal environment in the body
(maintaining the optimum biochemical
environment).
• Integration and regulation of growth and
development.
• Control, maintenance and instigation of sexual
reproduction, including gametogenesis, coitus,
fertilization, fetal growth and development and
nourishment of the newborn.
Types of cell-to-cell signaling
Classic endocrine hormones
travel via bloodstream to target
cells; neurohormones are
released via synapses and
travel via the bloostream;
paracrine hormones act on
adjacent cells and autocrine
hormones are released and act
on the cell that secreted them.
Also, intracrine hormones act
within the cell that produces
them.
Response vs. distance traveled
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.
Major hormones and systems
• Top down organization of endocrine system.
• Hypothalamus produces releasing factors that
stimulate production of anterior pituitary hormone
which act on peripheral endocrine gland to stimulate
release of third hormone
– Specific examples to follow
• Posterior pituitary hormones are synthesized in
neuronal cell bodies in the hypothalamus and are
released via synapses in posterior pituitary.
– Oxytocin and antidiuretic hormone (ADH)
Regulation of hormone secretion
 Sensing and signaling: a biological need is sensed,
the endocrine system sends out a signal to a target
cell whose action addresses the biological need. Key
features of this stimulus response system are:
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receipt of stimulus
synthesis and secretion of hormone
delivery of hormone to target cell
evoking target cell response
degradation of hormone
Some Specific Types of Chemical Signaling
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Hormones: chemicals released into the blood
stream, act at a distant site
Autocrine factor: chemical signal is released from
a cell type, and acts upon that same cell type
chemical
Some Specific Types of Chemical Signaling
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Paracrine factor: chemical is released from one
cell type, and acts locally on another cell type (in
same tissue)
chemical
Some Specific Types of Chemical Signaling
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Pheromone: chemical is released into the
environment, can affect other individuals
Some Specific Types of Chemical Signaling
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Neurotransmitter: chemical released into synaptic
cleft, influences postsynaptic cell
Neurohormone: chemical released from neuron into
bloodstream, acts at distant site
What determines the size of hormone effects?
1) The amount of hormone in the circulation
(reaching the target tissue)
- the more hormone, the greater the effect
2) The presence and number of receptors for that
hormone on the target tissue.
- no receptor, no response
- some receptors, some response
- many receptors, higher response
How do you regulate hormone levels?
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Hormones are generally not secreted at a constant
rate.
Regulation of hormone levels involves:
- regulation of hormone production
- regulation of hormone secretion (often a
separate step)
- sometimes, regulation of hormone metabolism
Mechanisms of Hormone Regulation
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Neural Regulation: neurons synapse with cells
producing hormone (ie, norepinephrine release from
the adrenal gland).
Endocrine Regulation: hormones bind to endocrine
cells, regulating release of another hormone (ie, FSH
stimulates estrogen release)
Regulation by other factors (humoral): endocrine
cells respond to levels of other factors in the
circulation (ie, glucose causes increased insulin
secretion from the pancreas)
Role of Feedback in Secretion
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The secretion of hormones is usually dependent
upon feedback mechanisms
Negative feedback: a stimulus causes an
endocrine response (hormone secretion) which
will decrease the level of that stimulus
Positive feedback: a stimulus causes a response
which will increase the level of that stimulus
Patterns of Hormone Secretion
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There are three basic patterns of secretion: pulsatile,
acute, and cyclic.
Pulsatile: relatively constant level of hormone, over a
long period
Acute: rapid increase in hormone level for a short
time in response to a stimulus
Cyclic: hormone increases and decreases in a
constant pattern
Patterns of Secretion
Pulsatile
Acute
Cyclic
Cyclic Increases in Reproductive Hormones
Rat Ovulatory Cycle
LH
Hormone
Level
E2
FSH
Diestrus Diestrus
Day 1
Day 2
Proestrus Estrus
How are hormones transported through the
body to their target cells?
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Some hormones are bound to proteins (binding proteins)
in the bloodstream
hormone + binding protein <----> complex
- hormone must unbind to act on tissues: binding affects
activity of hormone
- binding proteins may increase the time the hormone
stays in the circulation
-some binding proteins highly specific, some less specific
Other hormones circulate freely in the blood (no binding
proteins)
Where are Hormones Distributed to?
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Hormones are distributed in the general circulation
to all parts of the body that receive blood flow.
What is a half-life?
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Hormones are eventually broken down (metabolized)
and/or excreted from the body.
The rate of removal from the circulation is fairly
constant for a given hormone.
The length of time it takes to remove half of the
amount of hormone from the circulation is the halflife of that hormone.
Amount of Hormone
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100%
50%
0%
Time
What is a half-life?
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In general, water-soluble hormones have shorter halflives than lipid soluble hormones (rapid degradation in
kidney, liver, lungs)
Hormones with short half-lives exhibit rapid changes
in hormone levels.
Lipid soluble
0
30
Water soluble
60
0
TIME
30
60
Conjugation of Hormones
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Some hormones (ie, steroids) are modified by the
liver (conjugation).
Water-soluble groups are added on (sulfate,
glucuronic acid),decreasing activity and increasing
the water solubility of the hormone.
Increasing water solubility increases the rate at
which the hormone is excreted by the kidney.
Mechanism of Hormone Action: Receptors
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For hormones to act on a cell, that cell must have a
receptor for that hormone.
Receptors bind the hormone, resulting in a biological
response.
Receptors are found only in target tissues for that
hormone.
Receptors are very specific (they only bind a specific
hormone, not all hormones)
Receptors have high affinity for their hormone (bind
hormone at very low hormone concentration).
What Receptors Do
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Activate second messenger systems (cyclic AMP,
cyclic GMP).
Phosphorylate cellular proteins, affecting their
activity.
Control ion channels.
Regulate gene transcription.
Types of Membrane-Bound Receptors
Types of Receptors
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Membrane Bound: For hormones which do not enter
the cell, the receptor is on the surface of the cell
membrane. These typically affect second messengers,
kinases, and ion channels.
FSH
FSH
cAMP
protein
kinase
A
Types of Receptors (the other kind)
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Intracellular Receptor: Steroid hormones, thyroid
hormone, and vitamin D cross the plasma
membrane and bind to receptors within the cell.
This hormone:receptor complex binds DNA,
regulating gene expression.
E2
E2:R
E2:R:DNA
+,mRNA
protein
Regulation of Receptors
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The responsiveness of a target cell to a hormone is
dependent upon the number of receptors present.
By increasing or decreasing receptor number, you can
regulate the hormonal activity on the target cell.
Up-regulation: increase in receptor number due to
increased synthesis.
Down-regulation: decrease in receptor number due
to decreased synthesis and/or increased degradation.
More about receptors in the next lecture…
Next Lecture..…
Hormone Survey