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Chapter 17:. Functional Organization of the Endocrine System. Pg 586. Chapter 17 Outline. General Characteristics of the Endocrine System Chemical structure of hormones Control & secretion rate Transport & distribution in the body Metabolism & Excretion - PowerPoint PPT Presentation
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AP2 Chapter 17 1
Chapter 17:Functional Organization of
the Endocrine System
Pg 586
AP2 Chapter 17 2
Chapter 17 Outline
I. General Characteristics of the Endocrine System
II. Chemical structure of hormones
III. Control & secretion rate
IV. Transport & distribution in the body
V. Metabolism & Excretion
VI. Interaction of hormones with their target tissue
VII.Classes of Receptors
AP2 Chapter 17 3
I. General Characteristics of the Endocrine System
AP2 Chapter 17 4
I. General Char. of the Endocrine Syst.
Greek:• Endo: within• Krino: to secrete• Hormone: to set in motion
Endocrine System:• Composed of endocrine
glands that typically secrete chemical signals (a.k.a. hormones) into the cardiovascular system– Exocrine glands secrete
their products onto a surface
• Hormones are:a) Prod’d in small amounts
by a collection of cells
b) Secreted in interstitial spaces
c) Enters the cardiovascular system where it is transported some distance
d) Acts on specific tissues (target tissues) at another site in the body to influence the activity of these tissues in some specific fashion
5
I. General Char. of the Endocrine Syst.Endocrine System
• Hormones can be described as Amplitude-modulated Signals
• & in [ ] of hormones in body fluids over periods ranging from minutes to hours
• Responses are also or based on [ ]
Nervous System
• All or none potentials carried along axons can be described as frequency-modulated signals.
• These vary in frequency but not amplitude
• Low frequency weak stimulus• High frequency strong stimulus
• FX last only 1 to a few milliseconds
• Local actions
Regulate activities of structures in body but do so differently Intimate relationship btwn these 2 syst’s is now recognized
As always there are exceptions
AP2 Chapter 17 6
I. General Char. of the Endocrine Syst.Intercellular chemical signals (Table 17.1 pg 588)
1. Autocrine
2. Paracrine
3. Hormones
4. Neurohormones (AKA hormone)
5. NT/Neuromodulator
6. Pheromone
allows 1 cell to communicate w/ another Coordinate & regulate the activities of most cells
NT’s & neuromodulators play essential roles in fxn of the NSHormones are secreted by the Endocrine System
AP2 Chapter 17 7
I. G
ener
al C
har.
of th
e E
ndoc
rine
Sys
t.In
terc
ellu
lar
chem
ical
sig
nals
1. Autocrine
– Secreted by cells in a local area & influences the activity of the same cell type from which it was secreted
2. Paracrine– Prod’d by a wide variety of
tissues & secreted into tissues spaces; usually has a localized effect on others
3. Hormones– Secreted into the blood by
specialized cells; travels some distance to target tissues; influences specific activities
AP2 Chapter 17 8
I. G
ener
al C
har.
of th
e E
ndoc
rine
Sys
t.In
terc
ellu
lar
chem
ical
sig
nals
4. Neurohormones (AKA
hormone)– Produ’d by neurons but
function as hormones
5. NT/Neuromodulator– Prod’d by neurons & secreted
into extracellular spaces by presynaptic nerve terminals; travels short distances; influences postsynaptic cells
6. Pheromone– Secreted into the environment;
modifies the physiology and behavior of other individuals of the same species
AP2 Chapter 17 9
II. Chemical Structure of Hormones
Pg 589
Table 17.2 (Examples listed)
Figure 17.3
AP2 Chapter 17 10
II. Chemical Structure of Hormones
A. Proteins
B. Short sequences of aa’s called polypeptides
C. Derivatives of aa’s
D. Lipids
E. Glycoproteins
AP2 Chapter 17 11
III. Control of Secretion Rate
AP2 Chapter 17 12III. C
on
tro
l of S
ecr
etio
n R
ate
• Negative Feedback loops are used to help maintain the body in a state of homeostasis
• Positive Feedback loops is also used in a very limited capacity
Figure 17.7
AP2 Chapter 17 13
III. Control of Secretion Rate
3 major patterns of regulation1. Non-hormonal Regulation of hormone secretion
2. Nervous System regulation of hormone secretion
3. Hormonal regulation of hormone secretion
• As with everything in the body, it can be much more complicated involving multiple mechanisms
• Some hormones:– Are in circulatory system at relatively constant levels– D suddenly in response to stimulation– D in a relatively constant cycle
AP2 Chapter 17 14
III. Control of Secretion Rate3 major patterns of regulation
1. Non-hormonal Regulation of hormone secretion– Changes in the extracellular [ ] of a substance other than a
hormone effect the function of the endocrine gland
AP2 Chapter 17 15
III. Control of Secretion Rate3 major patterns of regulation
1. Neural Control of the endocrine gland– Neuron is synapsed with an endocrine gland and the neuron
influences the activity of the gland
AP2 Chapter 17 16
III. Control of Secretion Rate
3 major patterns of regulation3. Hormonal regulation of hormone secretion
– Control of the secretory activity of one gland by a hormone or neurohormone secreted by another gland.
AP2 Chapter 17 17
IV. Transport & Distribution in the body
AP2 Chapter 17 18
IV. Transport & Distribution in the body
1. Unbound Hormones 2. Bound Hormones
2 main ways to transport hormones in the blood
• Water soluble and travel in the blood
• Lipid soluble and do not like the watery environment of the blood thus it must be bound to a transport protein
Pg 594Fig 17.9
AP2 Chapter 17 19
IV. Transport & Distribution in the body
2. Bound Hormones• These are bound in a reversible
fashion• Equilibrium is established btwn
bound and their unbound counterparts
• Bound are also trapped within the confines of the capillary because they are to big to filter thru– These serve as a reservoir. Thus
when one in tissue is used there are replacements that only need to be released from the blood stream
– These can also remain in the blood longer without being destroyed
AP2 Chapter 17 20
IV. Transport & Distribution in the body
a. Lipid soluble hormones
• Pass thru capillary walls readily
• Typically travel bound to binding proteins
• Binding prevents their rapid diffusion from the circulatory system into the tissues
• Reservoir also gives a relatively constant rate of diffusion of the unbound hormone from circ.systm.
b. Water soluble hormones
• Must go thru the pores of the capillary walls (fenestrae)
• The capillaries of the organs regulated by and glands secreting these hormones usually have these large pores.
• These usually get into tissue at a slow rate
Hormones go thru the bld & thus distributed quickly throughout the body They diffuse thru the capillary wall & enter interstitial spaces and the rate of that movement varies by hormone
AP2 Chapter 17 21
V. Metabolism & Excretion
AP2 Chapter 17 22
V. Metabolism & ExcretionDestruction & elimination of hormones limit the time that they are active in the body. The body’s activities can or dependent on how long the hormone remains in the body
• Length of time it takes for ½ the dose of a substance to be eliminated from the circulatory system. (RATE)
• Time to eliminate entire amount isn’t helpful b/c it all depends on what you start with.
• Times vary dependent on specific hormone
Ways to lengthen half-life
• Binding them to binding proteins
• Their structures may also protect the hormone– Example– Glycoproteins: their carb
component protects them from proteolytic enzymes in circulatory system
Half-Life
AP2 Chapter 17 23
V. Metabolism & Excretion
4 major ways to remove hormones from bld
1. Excretion– Excreted into the urine by the kidney or the bile by the liver
2. Metabolism– Enzymatically degraded in the bld, liver, kidney, lungs, or
target tissues– Byproducts are excreted in the bile & urine
3. Active Transport– Actively transported into cells and used again later as a NT
or hormone
4. Conjugation– Substances are attached to hormones primarily in the liver.
These normally make the hormone less active & increase its rate of excretion
AP2 Chapter 17 24
VI. Interactions of hormones with their target tissues
25
VI. Interactions of hormones w/their target tissues
Hormones (a.k.a. Ligands)• Bind to receptors (proteins or glycoproteins)• Bind at the receptor site (binding site)
Binding Site:• Chemical characteristics of
the site allow only a specific type of chemical signal to bond to it
• “Specificity” can’t get growth hormone to bind to insulin site
• Hormone receptors have a high affinity for the hormones that bind them, thus only a small [ ] results in a significant # of receptors being bound
• Presence or absence of receptor determines wh/cells will react to the hormone’s release, thus it can travel throughout the body, but will only activate the proper cells
AP2 Chapter 17 26
VI. Interactions of hormones w/their target tissues
• Drugs can be designed to have a similar structure to a natural hormone & may compete for the receptor’s binding site
• Agonist:– Chemical that will bond to a receptor & activate it (Histamine)
• Antagonist:– Chemical that will bind to a receptor but inhibits its action
(antihistamine)
Taking advantage of hormone
shape to make drugs
AP2 Chapter 17 27
VI. Interactions of hormones w/their target tissues
• Can be constant or variable.• Rxns can decrease rapidly with time.
One Explanation:• Fatigue after prolonged stimulation of
targeted cells
Response to Hormone
AP2 Chapter 17 28
VI. Interactions of hormones w/their target tissues1. Down-regulation
– # of receptors can also decrease over time after exposure
– Tissues that down regulate are usually designed to respond to short term hormone increases
– Tissues that respond to constant levels of hormones do not exhibit down-regulation
2. Up-regulation– Periodic increases in
sensitivity of some cells to hormones
– Results from an increase in rate of receptor molecule synthesis
Fig
ure
17.
12 P
g 5
96
AP2 Chapter 17 29
VI. Interactions of hormones w/their target tissuesDown-regulation continued
2 ways of down regulation
1. Synthesis rate of the receptor are reduced
– Most hormone receptor complexes are degraded over time. If they are not replaced because of no synthesis the ultimate result is less cell surface receptors
2. Increased rate of receptor degradation
– Receptor hormone complexes are sometimes degraded more quickly than the receptor alone
AP2 Chapter 17 30
VII. Classes of Receptors
• 2 Major Categories of Hormones• 2 Major Categories of Receptors
(Figure 17.13 pg 597)
AP2 Chapter 17 31
VII Classes of ReceptorsA. Hormones that bind to
membrane bound receptors
• Include large molecules & water soluble molecules both can’t pass thru the plasma membrane
• Examples:– Proteins, glycoproteins,
polypeptides, smaller molecules (epi/norepi)
• When the receptor is bound it initiates a response inside the cell
• Thus they interact w/the outside of the cell with membrane bound receptors– Transmembrane receptors
w/their receptor sites exposed to the outer surface of the plasma membrane
32
VII Classes of ReceptorsB. Hormones that bind intracellular receptors
• These include lipid-soluble and relatively small hormones.
• Examples:– Thyroid hormones, steroid
hormones (testosterone, estrogen, progesterone, aldosterone, & cortisol)
• Diffuse thru the plasma membrane & bind to Intracellular Receptors.– These are receptors in the
cytoplasm or even the nucleus of the cell
• Thus the hormone-receptor complex interacts with the DNA directly to prod. a response.
AP2 Chapter 17 33
VII. Classes of Receptors2 Major Categories
Membrane Bound Receptors Intracellular Receptors
AP2 Chapter 17 34
VII. Classes of ReceptorsMembrane Bound Receptors
1. Receptors that activate G-proteins
2 major categories
Mechanisms for membrane bound receptors
2. Receptors that directly alter the activity of intracellular enzymes
AP2 Chapter 17 35
1. Receptors that activate G-proteins
• These have 3 subunits: , , a b& g
• Called G-proteins because a binds to guanine nucleotides
• Result #1:• Activated a-
subunit can alter the activity of molecules inside the cell prod’ing cellular responses
Fig 7.14 pg 599
AP2 Chapter 17 36
1. Receptors that activate G-proteins• Result #2:
• Activated a-subunit can combine w/ion channels causing them to open & close
• Some ions or molecules can act as intracellular modulators
• Enter or are synthesized w/in the cell that regulate enz activity in the cell
Fig 7.15 pg 600
AP2 Chapter 17 37
1. Receptors that activate G-proteins
• Result #3:• Activated a-subunit can also alter the activity of enz’s
inside the cell
Fig 7.16 pg 601
AP2 Chapter 17 38
1. Receptors that activate G-proteins
• Result #4:• Alter the [ ] of
intracellular mediators other than Ca2+ & cAMP
Fig 7.17 pg 602
AP2 Chapter 17 39
VII. Classes of Receptors
1. Receptors that activate G-proteins– When the hormone separates from the receptor
additional G-proteins are no longer activated– Inactivation of a-subunit occurs when phosphate
is removed from the GTP-leaving GDP with the a-subunit
– Then the subunits of the G-protein recombine
• Membrane Bound Receptors
AP2 Chapter 17 40
VII. Classes of ReceptorsMembrane Bound Receptors
1. Receptors that activate G-proteins
2 major categories
Mechanisms for membrane bound receptors
2. Receptors that directly alter the activity of intracellular enzymes
AP2 Chapter 17 41
2. Receptors that directly alter the activity of intracellular enzymes
• These receptor when bound directly alter the activity of an intracellular enzymes (mediators) w/no 2nd messenger needed
• Altered enz’s can be membrane bound or not
• Mediator enz’s act as chemical signals that move from where they are altered into the cytoplasm where they activate processes that prod a cellular response
Fig 7.18 pg 602
AP2 Chapter 17 42
2. Receptors that directly alter the activity of intracellular enzymes
• Altered enzyme activity can:a) or the activity of
intracellular mediator molecules
b) Results in the phosphorylation of intracellular proteins
c) Intracellular mediators (Phosphoylated proteins) activate processes that prod the response of the cell
Fig 7.18 pg 602
43
2. Receptors that directly alter the activity of intracellular enzymes
• Some are bound & a portion of the receptor on the inner surface of the membrane acts as a phosphorylase enzyme that phosphorylates several specific proteins– Phosphorylated proteins:
• Can be part of the membrane bound protein or not
• Influence the activity of other enzymes in the cell
AP2 Chapter 17
Fig 7.19 pg 603
44
2. Receptors that directly alter the activity of intracellular enzymes
Cascade Effect– Most hormones act
exponentially causing a pyramid effect that result in rapid responses
– Few mediator molecules activate several enz’s & each enz activates several other enz’s that prod a response
– An amplification system exists in wh/a few molecules can control the activity of many enz’s w/in the cell
AP2 Chapter 17
Fig 7.20 pg 604
AP2 Chapter 17 45
VII. Classes of Receptors2 Major Categories
Membrane Bound Receptors Intracellular Receptors
AP2 Chapter 17 46
VII. Classes of Receptors
• Lipid soluble hormones cross the plasma membrane into the cytoplasm or nucleus & bind to intracellular receptors by the process of diffusion
• Thus receptor location is in the cytoplasm or nucleus
Fig 7.21 pg 605
AP2 Chapter 17 47
VII. Classes of Receptors• Fxns of receptor-
hormone complex:a. Alter the activity of enz’s
of the cell
b. Bind to DNA to prod a response:• Via gene expression• DNA is transcribed into
mRNA then translated into a protein
• Thus it increases the synthesis of a specific protein.
Fig 7.21 pg 605
AP2 Chapter 17 48
VII. Classes of Receptors
• These types of rxns are not instant, they usually take several hours btwn hormone release & response is observed– To make mRNA & protein
• Hormone influence is limited via hormone-receptor complex degradation Fig 7.21 pg 605
AP2 Chapter 17 49
VII. Classes of ReceptorsIntracellular Receptors
Fig 7.21 pg 605