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PowerPoint® Lecture Slides
prepared by
Janice Meeking,
Mount Royal College
CHAPTER
16
The Endocrine
System:
Part A
Copyright © 2010 Pearson Education, Inc.
•
The term hormone is derived from a Greek verb meaning – to
excite or arouse
•
Hormone is a chemical messenger that is released in one tissue
(endocrine tissue/gland) and transported in the bloodstream to
reach specific cells in other tissues
•
Regulate the metabolic function of other cells
•
Have lag times ranging from seconds to hours
•
Tend to have prolonged effects
•
Hormone actions must be terminated – how?
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Intercellular communication types
• Autocrine - the cell signals itself through a chemical that it
synthesizes and then responds to. Autocrine signaling can
occur:
• solely within the cytoplasm of the cell or
• by a secreted chemical interacting with receptors on the
surface of the same cell
• Paracrine - chemical signals that diffuse into the area and
interact with receptors on nearby cells (cells within the same
tissue).
• Endocrine - the chemicals are secreted into the blood and
carried by blood and tissue fluids to the cells they act upon.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/Hormones.html
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Bloodstream
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Endocrine versus Nervous system
• Both use chemical communication
• Both are being regulated primarily by negative feedback
Neurotransmitters
Hormones
• Released in synapse
• Released to bloodstream
• Close to target cells
• Can be distant from target
cells
• Signal to release by
action potential
• Different types of signal
• Short live effect
• Long term effect
• Crisis management
• Ongoing processes
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Endocrine System: Overview
• Acts with the nervous system to coordinate and
integrate the activity of body cells
• Influences metabolic activities by means of
hormones transported in the blood
• Responses occur more slowly but tend to last
longer than those of the nervous system
• Endocrine glands: pituitary, thyroid, parathyroid,
adrenal, and pineal glands
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Endocrine System: Overview
• Some organs produce both hormones and exocrine
products (e.g., pancreas and gonads)
• The hypothalamus has both neural and endocrine
functions
• Other tissues and organs that produce hormones
include adipose cells, thymus, cells in the walls of
the small intestine, stomach, kidneys, and heart
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Hormone structure - based on chemical structure
• Two main classes
1.Amino acid-based hormones
Amino acid derivatives
• Structurally similar to amino acids
• Derivative of tyrosine : thyroid hormones
catecholamines (Epinephrine, norepinephrin,
dopamine),
• Derivative of tryptophan - melatonine.
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Hormone structure
• Peptide hormones – 2 groups
• Short polypeptides and small proteins – hormones
secreted by heart, thymus, digestive tract, pancreas,
hypothalamus (ADH and OT) and anterior pituitary
(ACTH, GH, MSH, PRL)
• Glycoproteins – consist more than 200 amino acids
and have carbohydrate side chains.
•
anterior pituitary (TSH, LH and FSH), kidneys
(erythropoietin), reproductive organs (inhibin)
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Hormone structure
2.Steroids (Lipid derivatives)
• Synthesized from cholesterol
• Gonadal and adrenocortical hormones
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A Structural Classification of Hormones
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Distribution of Hormones in bloodstream
• Hormones that are released into the blood are being
transported in one of 2 ways:
• Freely circulating
• Bound to transport protein
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Distribution of Hormones in bloodstream
• Freely circulating (most hormones)
• Hormones that are freely circulating remain functional for less
than one hour and some as little as 2 minutes
• Freely circulating hormones are inactivated when:
* bind to receptors on target cells
* being broken down by cells of the liver or kidneys
* being broken down by enzymes in the plasma or
interstitial fluid
• Bound to transport proteins – thyroid and steroid hormones
(>1% circulate freely)
• Remain in circulation longer
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Hormone Concentrations in the Blood
• Concentrations of circulating hormone reflect:
• Rate of release
• Speed of inactivation and removal from the body
(clearance rate)
• Hormones are removed from the blood by:
• Degrading enzymes
• The kidneys
• Liver enzyme systems
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Metabolic clearance rate (MCR)
• Defines the quantitative removal of hormone from
plasma
• The bulk of hormone is cleared by liver and kidneys
• Only a small fraction is removed by target tissue
• protein and amine hormones bind to receptors and are
internalized and degraded
• Steroid and thyroid hormones are degraded after
hormone-receptor complex binds to nuclear chromatin
• 99% of excreted hormone (!) is degraded by enzyme
systems
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Mechanisms of Hormone Action
• Hormone action on target cells
1. Alter plasma membrane permeability of
membrane potential by opening or closing ion
channels
2. Stimulate synthesis of proteins or regulatory
molecules
3. Activate or deactivate enzyme systems
4. Induce secretory activity
5. Stimulate mitosis
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Receptors for hormones are located:
• The hormone must interact with a specific receptor in
order to affect the target cell
• In the cell membranes of target cells
• In the cytoplasm or nucleus
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Mechanisms of Hormone Action
•
Two mechanisms, depending on their chemical nature
1. Water-soluble hormones (all amino acid–based hormones
except thyroid hormone)
•
Cannot enter the target cells
•
Act on plasma membrane receptors
•
Coupled by G proteins to intracellular second
messengers that mediate the target cell’s response
2. Lipid-soluble hormones (steroid and thyroid hormones)
•
Act on intracellular receptors that directly activate
genes
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Indirect effect – through G-protein and 2nd messenger
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Receptors on the cell membrane
• Hormones do not induces changes in cell activity
directly but via the induction of the appearance and
action of other agents
• Hormones are referred to as first messengers and the
agents that are activated by the hormones are called
second messengers.
• All amino-acid hormones (with exception of the thyroid
hormone) exert their signals through a second messenger
system:
• cAMP
• PIP
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Receptors on the cell membrane
• Second messengers function as enzyme activator,
inhibitor or cofactor
• A small number of hormone molecules induce the
appearance and activity of many 2nd messenger
molecules – amplification
• one single hormone can induce the activation of
more than one 2nd messenger
• Activation of a 2nd messenger can start a chain of
reactions – receptor cascade
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Amino Acid-Based Hormone Action: cAMP Second Messenger
• Hormone (first messenger) binds to its receptor, which
then binds to a G protein
• The G protein is then activated
• Activated G protein activates the effector enzyme
adenylate cyclase
• Adenylate cyclase generates cAMP (second messenger)
from ATP
• cAMP activates protein kinases, which then cause cellular
effects
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Amino Acid-Based Hormone Action: PIP-Calcium
• Hormone
G protein
binds
to
the
receptor
and
activates
• G protein binds and activates phospholipase
• Phospholipase splits the phospholipid PIP2 into
diacylglycerol (DAG) and IP3 (both act as second
messengers)
• DAG activates protein kinases; IP3 triggers release of
Ca2+ stores
• Ca2+ (third messenger) alters cellular responses
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Intracellular Receptors and Direct Gene
Activation
• Steroid hormones and thyroid hormone
1. Diffuse into their target cells and bind with intracellular
receptors
2. Receptor-hormone complex enters the nucleus
3. Receptor-hormone complex binds to a specific region of
DNA
4. This prompts DNA transcription to produce mRNA
5. The mRNA directs protein synthesis
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Location of
Receptor
Classes of
Hormones
Principle
Mechanism of Action
Cell surface
receptors (plasma
membrane)
Proteins and
peptides,
catecholamines
and eicosanoids
Generation of second
messengers which
alter the activity of
other molecules usually enzymes within the cell
Intracellular
receptors
(cytoplasm and/or
nucleus)
Alter transcriptional
Steroids and
activity of responsive
thyroid hormones
genes
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/moaction/change.html
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Target Cell Specificity
• Hormones circulate to all tissues but only activate cells referred to
as target cells
• Target cells must have specific receptors to which the hormone
binds
• These receptors may be intracellular or located on the plasma
membrane
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Interaction of Hormones at Target Cells
• Three types of hormone interaction
• Permissiveness – one hormone cannot exert its effects without
another hormone being present
• For example, thyroid hormone increases the number of
receptors available for epinephrine at the latter's target cell,
thereby increasing epinephrine's effect at that cell. Without
the thyroid hormone, epinephrine would only have a weak
effect
• Synergism – more than one hormone produces the same
effects on a target cell
• Antagonism – one or more hormones opposes the action of
another hormone
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Target Cell Activation
• Hormone exert their effects on target cells at very low blood
concentrations (ng-10-9 gr; pg-10-12 gr)
• Target cell activation depends on three factors
• Blood levels of the hormone
• Relative number of receptors on the target cell
• The affinity of those receptors for the hormone
• The time required to effect target cells depends on the
hormone - some influence immediately and some (steroids;
why?) require hours or days
• Hormone effect duration also varies and can range between
seconds to hours
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Receptors number on target cell
• down regulation – the presence of the hormone induces a decrease in
the receptors concentration;
• high levels of hormone – cell less sensitive
• Up regulation – absence of the hormone induces the increase in
receptors concentration;
• Low levels of hormone – cell more sensitive
• In most systems the maximum biological response is achieved at
concentrations of hormone lower than required to occupy all of the
receptors on the cell (spare receptors).
• Examples:
• insulin stimulates maximum glucose oxidation in adipocytes with
only 2-3% of receptors bound
• LH stimulates maximum testosterone production in Leydig cells
when only 1% of receptors are bound
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Control of Hormone Release
• Blood levels of hormones:
• Are controlled by negative feedback systems
• Vary only within a narrow desirable range
• Hormones are synthesized and released in response to:
• Humoral stimuli
• Neural stimuli
• Hormonal stimuli
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Humoral Stimuli
• Secretion of hormones in
direct response to changing
blood levels of ions and
nutrients
• Example: concentration
calcium ions in the blood
of
• Declining
blood
Ca2+
concentration stimulates the
parathyroid glands to secrete
PTH (parathyroid hormone)
• PTH
causes
Ca2+
concentrations to rise and
the stimulus is removed
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Neural Stimuli
• Neural stimuli – nerve fibers
stimulate hormone release
• Preganglionic sympathetic
nervous system (SNS) fibers
stimulate the adrenal medulla
to secrete catecholamines
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Figure 16.5b
Hormonal Stimuli
• Hormonal stimuli – release of
hormones in response to
hormones produced by other
endocrine organs
• The hypothalamic hormones
stimulate
the
anterior
pituitary
• In turn, pituitary hormones
stimulate targets to secrete
still more hormones
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