Download Chapter 18 Endocrine system

Chapter 18 Endocrine system
Intercellular communication
there are several trillion cells in the human body
these cells are organized into the four basic tissues of the body
the four tissue types are organized into the organs of the body
each organ performs vital functions that support the life of the
organism
the vital functions that are performed by each organ depends on several
forms of communication
1. chemical synaptic communication
occurs across a synapse
is mediated by neurotransmitters
is very limited to specific postsynaptic cells
target cell must have receptor for the neurotransmitter
and form a synapse with presynaptic cell
is the major mechanism for rapid long-distance
communication between the nervous system and the
peripheral organs and tissues
is rapid (milliseconds) but is short-term (lasts seconds
to minutes)
2. electrical synaptic (direct) communication
occurs across gap junctions
is mediated by small molecules like ions
is a rapid form of communication
effect is limited only to cells attached by gap junctions
and typically is a local effect
sometimes effect travels a long distance as seen in glia
and smooth muscle etc..
used to:
coordinate ciliary movement
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facilitate propagation of action potentials
coordinate contractions of the heart
3. autocrine communication
occurs when chemical signals are released by cells and have a
local effect on the same cell type even the very same cell
mediated by chemicals called cytokines (local
hormones) which are released into the extracellular
fluid
effect is limited to cells located in the small area near the release
of factors
target cells must possess the specific cytokine
receptor
thus not all cells will respond
is a moderately rapid form of communication
4. paracrine communication
occurs when chemical signals are released by cells and have a
local effect on other types of cells
mediated by chemicals called cytokines (local
hormones) which are released into the extracellular
fluid
effect is limited to cells located in the small area near the release
of factors
target cells must possess the specific cytokine
receptor
thus not all cells will respond
prostaglandins are the most common type of cytokine
for both auto and paracrine communication
is a moderately rapid form of communication
5. endocrine communication
Occurs when chemical signals are released by cells into the
blood stream
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is mediated by factors called hormones
the major hormones are released from specialized tissues called
endocrine glands or endocrine cells
most tissues produce hormones
has a wide spread effect on numerous target cells typically
located at distant tissues and organs
theoretically all cells in the body are exposed to the
hormones but to be a target cells of the hormone the
cell must possess the specific hormone receptor
is the major mechanism for slow but sustained
communication between organs
characteristics of the endocrine system
endocrine system along with the nervous system are the two major, interrelated,
controlling systems of the body
neural control operates almost instantaneous
endocrine system provides a slower but long-lasting control
Endocrine tissue is typically organized into endocrine glands
these are ductless glands that release chemicals,
1. the chemicals are called hormones, or ligands
2. they are released in minute amounts into the interstitial spaces
3. the hormone enters the blood stream, via large permeable
fenestrated capillary bed, where it is dispersed throughout the body
* entering the blood stream is a definitive characteristic of a
hormone
4. the hormone will exit the blood stream at permeable capillary beds
some distance from the production site
5. the hormone next binds to target tissues which is any cells
expressing a specific high affinity receptors for the hormone
6. hormone binding to it’s receptor alters the production of second
messenger molecules (stimulate or inhibit) within the cell will alter the
activity of the target tissue
the second messengers will alter cell structure and/or function
by changing the
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1. types of proteins made by the cell (enzymes and the
structural proteins)
2. and/or amount or proteins made by the cell
3. and/or activity (on or off) of the enzymes and the
structural proteins when in the cell
because the target cells can be in several locations a single
hormone can affect the metabolic activities of
multiple tissues and organs simultaneously
a particular type of cell will have receptors for numerous hormones and
cytokines
thus control of cell function results from the interactions of numerous
hormones and cytokines
Target cells sensitive to several hormones may show interactive effects.
1.Permissive effects - first hormone enhances the effect of a later
hormone action. The effects are additive
a. estrogen up-regulates progesterone receptors in uterus
b. thyroid increases effect of epinephrine on breakdown of
triglycerides in adipocytes
2.Synergistic effects - two hormones acting together have a greater
effect than the sum of the effects of each hormone acting independently.
The effects are more exponential
a. both FSH and estrogen necessary for normal oocyte
development
b. FSH and testosterone together produce more sperm than
alone
3.Antagonistic effects - one hormone opposes the action of the other
hormone
a. insulin and glucagon
What types of cellular functions do the hormones of the endocrine system control?
1. reproduction
2. growth
3. development
4. activates body defenses
5. maintenance of electrolytes and water
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6. nutrient balance
7. cellular metabolism
Endocrine tissue s:
1. most endocrine glands are made of glandular epithelium
2. a few glands in the brain are made of modified neurons these are called
neurosecretory tissue or neuroendocrine tissue
the major endocrine glands include;
1. pituitary
2. thyroid
3. parathyroid
4. adrenal
5. pineal
6. thymus
other organs with major endocrine functions
7. ovaries and testes
8. pancreas
9. hypothalamus:
also has important neuronal functions
thus is called a neuroendocrine organ
most organs have a small amount of endocrine tissue producing hormones
certain tumor cells will produce high levels of hormones. This is more common
in cancers of the lung, pancreas, and some brain tumors
chemical classes of hormones:
three classes
1. lipid derivatives
a) Steroid hormones
made from cholesterol
1. gonadal hormones (sex hormones)
estrogens & progestins androgens
2. adrenocortical hormones
cortiosteroids
3. kidneys
calcitriol
b) eicosanoids
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derived from arachidonic acid-- a 20 carbon
fatty acid. has a five carbon ring at one end
primary role is as a autocrine and paracrine factor
secondary role as a hormone
leukotrienes
released by leukocytes to activate the
bodies defenses and coordinate tissue
response to injury
prostaglandins
produced by most tissue to coordinate
local cellular activity
have many roles including
clotting of blood and
regulation of blood flow
2. amino acid derivatives or biogenic amines
are constructed from the amino acids tyrosine and tryptophan
tyrosine derivatives includes
catecholamines
epinephrine
norepinephrine
dopamine
thyroid hormones
tryptophan derivatives include
melatonin
3. Peptide hormones
are constructed of chains of amino acids
typically synthesized as an inactive prohormone that is
converted to the active hormone just before or shortly
after secretion
two major groups
glycoprotein hormones
are larger (over 200 amino acids)
have carbohydrate side chains
includes
thyroid-stimulating hormone
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luteinizing hormone
follicle-stimulating hormone
others
none glycosolated peptide and protein homones
are smaller 9 amino acids to 198
are simple chains of amino acids
includes
antidiuretic hormone
oxytocin
growth hormone
prolactin
all hormones from
hypothalamus
heart
thymus
digestive tract
pancreas
Hormone transport in the blood steam
in the blood most hormones are bound to carrier or transport proteins including albumin
or specific globulins synthesized by the liver
this is not a requirement for hydrophilic hormones
steroid hormones, thyroid and eicosanoids are hydrophobic and must bind to a
carrier protein
typically the bloodstream will contain a substantial reserve of these
bound hormones
hormones that don’t have a carrier or are not bound to the carrier last only minutes and
are quickly broken down by the liver or kidneys or are broken down by enzymes in the
plasma or interstitial fluids
liver disease can have great impact on endocrine function due to a lack of
production of transport proteins
liver and kidney disease can reduce the clearance rate of hormones
typically damage to one organ is offset by increased removal by the
other
Factors that trigger the release of hormones
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1. humoral stimuli
release in response to changing of blood levels of
certain ions or nutrients (humoral stimuli).
example insulin and blood glucose levels
2. neural stimuli
some glands are innervated by nerve fibers
example: stimulation of the sympathetic
nervous system causes release of nor and
epinephrine from the adrenal medulla
the nervous system can undergo extreme conditions
and override all other systems controlling hormone
release
example: blood glucose is normally at 80 120 mg per 100 mls glucose but under high
sympathetic tone, glucose levels can rise
much higher
the nervous system is the
over-all controller of the endocrine system
3. hormonal stimuli
most endocrine glands release their hormones in
response to other hormones
example: most of the hormones released
from the pituitary gland act to stimulate the
release of hormones from other glands
regulation of hormone release by hormonal stimuli
Control of hormone production is carefully regulated so that there
tissues are not over stimulated (hypersecretion) of under stimulated
(hyposecretion)
1. negative feedback loop controls the amount of hormone
release for most hormones
1. stimulus results in hormone release
2. as hormone levels rise in the blood stream the release of
more hormones is inhibited
3. results in hormone levels varying only slightly
example:
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1. stress increases CRH from hypo
2. this increases ACTH release form pituitary
3. next the adrenal cortex will release glucocorticoids
4. as glucorticoid levels rise they inhibit the release of
more ACTH and CRH
2. positive feed back loops example estrogen and luteinizing hormone
ever increasing estrogen levels prior to ovulation stimulate an
increase in LH levels until ovulation occurs and a sharp rise in
progesterone inhibits LH
Modulation of hormone sensitivity
up-regulation
a cell can increase the number of hormone receptors and become more
sensitive
mechanism
increased synthesis of receptors
reduced rate of degradation of receptors
for example: oxytocin receptors are up-regulated at the time of
childbirth
also when a specific hormone’s levels drop it’s receptor numbers may
up-regulate
down-regulation
a cell can decrease the number of hormone receptors and become less sensitive
to a hormone
mechanism
1. reduce synthesis of receptors
2. increase rate of degradation of receptors
common when cells are exposed to chronically high concentrations of a
hormone
for example: high levels of insulin down regulate the insulin
receptor on adipocyte cells
Mechanisms of hormones actions
To affect a target cell a hormone must first interact with an appropriate receptor
Each cell has receptors to several different hormones
cells in different tissues have different combinations of receptors
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There are two types of hormone receptors
Membrane-bound receptors
Work by stimulating second messenger production
Intracellular hormone receptors
Work by direct gene activation
1. Membrane -bound receptors
some hormones (ligands) can not cross the through the plasma membrane they
are to large and water-soluble
they have receptors located in the plasma membrane and utilize second
messenger systems to convey their signal into the cell
cAMP second messenger cascade
cAMP serves as a second messenger in two ways
1. some hormones stimulate it’s production
2. some hormones inhibit it’s production
stimulation of cAMP production
1. hormone binds to specific high affinity receptor (ex: beta 1
epinephrine receptor)
hormone is called the first messenger
2. hormone-receptor complex activates Gs-protein (stimulatory)
3. the G-protein is temporarily activated when it exchanges GDP + Pi
for GTP
4. activated Gs-protein binds to a plasma membrane bound protein
called Adenylate cyclase activating the cyclase
5. the activated cyclase takes ATP and produces many cAMP
molecules
cAMP is called the second messenger
is the first substance free to move into the cell’s interior
6. cAMP binds to Protein Kinase A and activates the kinase
7. the Kinase A will add phosphate groups to target proteins within the
cell
this may activate enzyme
inactivate an enzyme
may open an ion channels (increases its activity)
close ion channels
activate a transcription fact to turn on protein synthesis
etc.
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cells respond differently to the cAMP because they contain different
types of target proteins that are phosphorylated by PKA
how to turn off the system
1. first must remove the hormone from the receptor
this occurs when the hormone is no longer being
released and is removed by the liver and kidneys
2. cAMP is brokendown by phosphodiesterase (PDE) in the
cell
3. phosphate groups on target proteins are removed by
phosphotases
4. GTP that bound to G-protein will be breakdown to GDP +
Pi so can’t stimulate the cyclase
why such a complicated method
several steps of amplification
several places for regulation
hormones that increase cellular levels of cAMP
beta 1 epinephrine receptor
ADH
ACTH
FSH
LH
TSH
Decrease levels of cAMP (inactivation of adenylate cyclase)
1. hormone binds to receptor (alpha 2)
2. receptor activates G-protein (inhibitory)
3. G-protein I binds to GTP and is temporarily activated
4. active G-protein I binds to adenylate cyclase and blocks its
ability to make cAMP
hormones that decrease cellular levels of cAMP
alpha 2 type of norepinephrine receptor
beta 2 type of epinephrine receptor
3. IP3/ calcium second messenger cascade
1. hormone binds to its receptor
2. receptor activates G-protein
releases GDP binds to GTP
3. G-protein activates the enzyme phospholipase C (PLC)
4. PLC generates two second messengers by cleaving phosphatidly inositol
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1. diacylglycerol
2. inositol triphosphate (IP3)
role of IP3
5. IP3 triggers the release of calcium from the endoplasmic reticulum
6. Calcium binds to calmodulin and activates it
7. activated calmodulin can bind to and activate specific enzymes
role of diacylglycerol
8. diacylglycerol along with calcium activate protein kinase C (PKC)
9. PKC phosphorylates target proteins
used by
oxytocin
epinephrine and norepinephrine alpha 1 receptors
2. Intracellular hormone receptors
Direct gene activation
lipid soluble hormones like steroid hormones and thyroid hormone
(not lipid soluble) can diffuse into their target cell
these types of hormones have their receptors located in the cytoplasm
or inside the cell nucleus
direct gene activation cascade
1. hormone diffuses into the cell and binds to receptor
2. hormone-receptor complex is translated to the nuclear
chromatin
3. the complex binds to a specific acceptor protein associated
with the DNA called a hormone-responsive element which is
attached to the promoter region of a gene
4. this interaction turns on a specific genes producing a
mRNA molecule
5. the mRNA is translated to a protein
protein maybe a structural protein or an enzyme
the hormone/receptor complex is broken down by enzymes
which will terminal the response
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