Transcript Document

The endocrine system
Chapter Readings
Chapters 74-77;
Chapter 79 pgs 979-980;
985-992
Lecture outline
I.
Overview of basic hormone action
A. Receptors
B. Fate of hormones
II. Hormone classification
A. Steroid
1. Characteristics
2. Mode of action
B. Protein/peptide/amines
1. Characteristics
2. Examples of amines
3. Mode of action
2
“Trigger” mechanisms for hormone release
A. Neural
B. Humoral
C. Hormonal –H-P-X axis
1. Review of H-P relationship
a. Hormones of anterior pituitary
b. Hormones “from” the posterior
pituitary
c. Hypothalamic-hypophyseal
connections
IV. H-P-T axis
A. Negative Feedback mechanisms
B. Negative feedback at ALL levels
C. Disruption of pathway—what happens to
hormone levels?
III.
3
V.
Thyroid Gland
A. Microscopic structure/follicles
B. Synthesis of TH
C. Actions of TH
D. Disorders of the thyroid gland
1.Diagnosing the problem
2. Hyperthyroidism
3. Hypothyroidism
E. Review of thyroid pathology
4
VI.
VII.
VIII.
Adrenal glands- H-P-A- axis
A. Anatomical review
B. Adrenal cortex
1. Glucocorticoids
2. Mineralcorticoids
a. Aldosterone (TBC- unit 4)
C. Corticosterone follows HPA axis neg. feedback control
D. Effects of corticosterone
E. Pathophysiology of HPA
1. Deficiencies
a. Addison’s- primary adrenal insufficiency
b. Secondary adrenal insufficiency (pit. problem)
2. Excess
a. Cushing’s disease (Pit is problem)
b. Cushing’s syndrome (ectopic tumor/iatrogenic)
i. Primary hyperadrenalism (tumor on
adrenal glands)
3. CAH- excess and deficiency
Growth Hormone
Parathyroid Hormone/ calcium regulation
5
• The endocrine system is a series of glands that
release a hormone into the plasma, where it is
dissolved and transported throughout entire body
within 60 seconds. Every cell is exposed to the
hormone, but not every cell responds to it. The cell must
have a functional hormone receptor. A cell that
responds will do so in various ways. The cells in the
heart, pancreas, and brain respond to epinephrine
differently. One thing that always happens is that a cell
will change its physiology in response to a hormone.
It will do something different, depending on the genes of
the cell in that organ.
6
• Hormones can be synergistic; aldosterone and
ADH both help increase volume of fluid in body.
Some hormones are antagonists; Atrial
natriuretic peptide (ANP, produced by heart
cells) is the opposite of ADH, and makes you
urinate more. Some hormones are permissive;
you need one around in order for a second to do
its job well. Thyroid hormone is permissive for
growth hormone. Not enough thyroid hormone
can cause stunted growth, even if enough
growth hormone is present.
7
Basic hormone action
– Made by the gland’s cells, possibly
stored, then released
– Circulate throughout the body
vasculature, fluids
• Basic hormone action
– Influences only specific tissues:
–target
Circulate
throughout
the body
cells that
have receptor
for
in blood vessels
hormone
only
specific
tissues
– –A Influences
hormone can
have
different
effects
on different
target
cells:
– target
cells that
have
depends
onfor
thehormone
receptor
receptor
– –Effects
dependcan
on the
A hormone
have different
preprogrammed
response
the
effects on different
targetofcells
target cells- hormones are merely
–molecular
Effects depend
on the
“triggers”
preprogrammed
of
– Some
hormones areresponse
“permissive”
cellshormones
forthe
thetarget
actions
of another
(T3 forare
GH)
molecular
“triggers”
Ultimatemerely
goal: alter
cell activity
by
altering protein activity through gene
expression or through altering
phosphorylation
Hormones
What would happen if there
was a defect in the gene code
for a particular hormone, or a
defect in the cell’s machinery
to make the hormone?
http://www.megalo-media.com/art/ccolor3.html
•
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• A target cell is only a target cell if it is has a
functional receptor (a protein). At home, you may
watch TV with either a cable or satellite dish. Satellite
waves are exposed to those homes with cable, but only
those with dishes receive the signal. The target cell’s
receptor serves to transduce (convert) the signal into a
response. Receptors are proteins, which can be inside
the cell or on its membrane. What would happen if there
were a gene defect in the DNA code for a receptor? The
receptor becomes faulty. The receptor will also not
function properly if the cell is exposed to excess salt,
heat, or pH.
9
What is a “receptor”?
• It is a protein made by the target cell
(protein synthesis, gene expression)
• Inserted into plasma membrane, or
found in cytoplasm or nucleoplasm
• Active site “fits” the hormone
• Acts to convert or “transduce” the
signal into a response
What would happen if there were a gene defect in the DNA
code for a receptor?
What would happen if the receptor protein was denatured?
10
• Endocrine glands secrete hormones into
the plasma. Then, several different events
could occur. It could bind to its receptor on
the target cell, causing a change. Or, it
could be destroyed by enzymes in the
plasma. It could land in the kidneys and be
filtered out before reaching its target.
11
What happens to a hormone once it’s secreted?
Carrier-bound
hormone
Endocrine
cell
•
•
•
•
Degraded in bloodstream
May be activated (e.g. T4)
May be excreted by kidneys/ liver
May reach a target cell and cause
a cell response
• May need carrier to reach target
cell
Free
Hormone
Hormone
Degradation or
removal
Hormone
receptor
Biological
effects
12
Classes of Hormone
•
•
•
•
•
•
•
Steroids (the only one that is
hydrophobic)
Amino Acid Derived
Peptides (<100 AA)
Proteins (>100 AA)
The smallest categories are the
AA derived and steroids.
The largest categories are the
peptides and proteins.
Study Tip: You don’t have to
memorize which hormones are in
which category, just memorize
those in the smallest category,
and the rest are peptides and
proteins. “DENTONE” stands for
those in the short categories:
DENT stands for the AA derived
hormones: Dopamine,
Epinephrine, Norepinephrine, and
Thyroid hormone . “ONE” stands
for hormones that end in “one”,
such as testosterone,
progesterone. They are all steroid
derived. The only steroid hormone
that does not end in “one” is
estrogen.
13
Steroid
hormones
are synthesized
from cholesterol, are
lipids
Hydrophobic,
lipophilic
Require a transport
protein to be carried
in bloodstream

• Long lasting effects: dissolve in body fat stores,
long “half life”
• Can “go all the way” across cell and nuclear
membranes to bind receptor
• Act directly on gene transcription
14
Steroid Hormones
• Steroid hormones are synthesized from cholesterol,
are hydrophobic, and require a transport protein in
plasma. They all have rings, which make it lipophylic
(hydrophobic). Examples of steroid hormones are
cortisol, aldosterone, testosterone, and estradiol. Steroid
hormones have long-lasting effects, dissolve in body
fat stores, and a long half life. Their receptor will be
inside of cell since they are the only class of hormone
that can get through cell membranes by themselves. A
steroid receptor is usually all the way in the nucleus,
although it may have a receptor in the cytoplasm, in
which case, it will then continue on into the nucleus. How
does it change the physiology of the cell? Steroid
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hormones act directly on DNA (gene) transcription.
• There is one other hormone (Thyroid hormone)
that has its receptor all the way in the nucleus,
yet it is not a steroid. Thyroid hormone is AA
derived, but its side chain has a hydrophobic
ring made out of two Tyrosine amino acids,
making thyroid hormone hydrophobic as
well. Thyroid hormone also effects DNA (gene)
transcription. Thyroid hormone is AA derived,
but it behaves like a steroid. Steroids effect
the genes.
16
Figure 74-6; Guyton & Hall
Steroid hormones and Thyroid Hormone
• These use intracellular receptors
• Steroid hormones enter cells, bind to cytoplasmic receptor and
together, these enter nucleus to have direct effects on DNA
transcription. Result: new cell proteins are made.
• Thyroid hormone “goes all the way” to the nucleus, binds to nuclear
receptor, and has direct effects on DNA transcription. Result: new cell
proteins are made.
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Protein/Peptide/AA-Derived Hormones
(except Thyroid hormone)
• Hydrophilic, don’t need a plasma protein carrier.
Their receptors are not inside of cells, they are
an integral protein that goes through the cell
membrane. The hormone binds to the outside,
signal is sent into the cell. A series of second
messengers are involved in this signal
transmission. Second messer systems are not
the first chemical messenger (that is the
hormone). There are three common ones: Cyclic
ATP, IP3-DAG, and Enzyme-linked type. You
will learn the details of these in the second unit.
18
• Second messengers change the physiology of a
cell by this: a protein called a kinase is activated.
The kinase adds phosphate groups onto the
protein. This alters the protein’s activity, usually
by supercharging it, like drinking 6-pack of Red
Bull. Very efficient. Not all of them become
supercharged, sometimes they are suppressed.
When a protein is phosphorilated, its activity is
changed. The cells activity will then change. All
hormones have the same end result, it alters the
physiology of the cell.
19
Protein/peptide/ Amine -based hormones
• Hydrophilic/ lipophobic
• May not require a
transport protein, soluble
in water (usually).
• Must bind receptor on the
target cell membrane and
trigger second
messengers to change
physiology of target cell.
• Exception is TH! Behaves
like a steroid.....
Figure 74-2;
Guyton & Hall
20
Synthesis of Amine Hormones
• Tyrosine can be turned into Dopamine,
norepinephrine, epiniephron, and thyroid
hormone. Norepi is primarily used as a
neurotransmitter. It is also used as a
hormone. Epi is primarily used as a
hormone, but it can be used as a
neurotransmitter. The diff between the two
is a methyl group. They are similar in
effect on a target cell.
21
Synthesis of Amine Hormones
tyrosine
hydroxylase
Tyrosine
L-Dopa
dopa decarboxylase
Dopaminergic
Dopamine
Neurons In
hypothalamus
dopamine  hydroxylase
Adrenergic Neurons
in adrenal medulla Norepinephrine
phenylethanolamineN-methyltransferase
Epinephrine
Adrenal Glands
Thyroid Hormones
Thyroid Gland
22
Signal Transduction systemsgive amplification
These are just some examples!
Scientists continue to discover more
pathways
23
What triggers hormones to be released?
HUMORAL
NEURAL
HORMONALH-P-X acis
Insulin and glucagon
24
What triggers hormone release?
There are three different mechanisms
• Neuronal Trigger
• The hormone is made in a neuron, is
transported down the axon and stored in
the synaptic knob. It is released from there
into the bloodstream, where it is carried to
the target cell. Examples are oxytocin,
ADH, Epinephrine.
25
• Humoral Trigger
• Something in the blood is being monitors,
stimulates the relese of the hormone. Insulin,
glucagon, parathyroid hormone. When you eat,
glucose gets high, releases insulin. Glucose is
low, glucagon released. Low calcium in blood for
parathyroid gland, targets intestinal cells to
absorb more calcium, and kidneys to reabsorb
more ca, and stimulates osteoclasts to degrade
bone matrix and ca goes into blood.
26
• Hormonal Trigger
• One endocrine gland releases a hormone
that stimulates another endocrine gland to
release its hormone.
27
•
• The hypothalamus is like a mom, her small child is like
the pituitary gland, her older child doing homework is like
the thyroid gland. None can move, only their
messengers can take their message from one to the
other. Mom sends the young child to tell the older one to
get his homework done. She hears the young child
passing the message, but after a while, the homework is
not presented to her, so tension builds up in her, and she
sends the messages more loudly until she is presented
with the finished homework.
28
• This is what happens in the body.
• Hypothalamus makes TSH-RH (thyroid
stimulating hormone releasing hormone)
• Pituitary makes TSH (thyroid stimulating
hormone)
• Thyroid gland makes TH (thyroid
hormone)
29
• The hypothalamus releases its hormone (TSH-RH) to the pituitary,
telling the pituitary to release its hormone (TSH), which tells the
thyroid gland to release thyroid hormone (TH). When thyroid
hormone is released, some of it will bind to receptors in the
hypothalamus, and the hypothalamus will stop releasing TSH-RH.
Until the receptors in the hypothalamus are bound with the resulting
thyroid hormone, the hypothalamus is not satisfied that there is
enough thyroid hormone present. The pituitary tells the
hypothalamus that it sent its signal to the thyroid gland, so they
hypothalamus is appeased for a while. But, until the target cell
(thyroid gland) changes its physiology (releases thyroid hormone),
the hypothalamus will continue to release its signal (TSH-RH).
When Thyroid levels are high enough, it will turn off its signal.
30
Hypothalamic Control of Hormone Secretion
Neural and hormonal control
ACTH adrenocorticotropic H
TSH thyroid-stimulating H
GH growth hormone
PRL prolactin
FSH follicle-stimulating H
LH luteinizing H
MSH melanocyte-stimulating H
Neural control
hormonal
31
Hypothalamic Control of Hormone
Secretion from the Adenohypophysis
•
•
•
Hypothalamus regulates secretion of
hormones
Almost always controlled by negative
feedback loops
– Blood concentration declines below a
minimum
• More hormone is secreted
– Blood concentration exceeds
maximum
• Hormone production is halted
Secreted like neurotransmitters from
axon terminals
– Secretes releasing factors to
release hormones
– Can also secrete inhibiting
hormones to turn off secretion of
hormones
32
What if the hypothalamus released its signal and the
thyroid released too much hormone?
• The hypothalamus will stop releasing its
hormone. This is a negative feedback
signal.
• When very few TH receptors are bound
on the hypothalamus, it will keep releasing
its hormone. When its thyroid receptors
are saturated, will stop.
33
• All cells respond to thyroid hormone,
increasing their metabolic rate (more gene
expression, heart speeds up, beats with
greater force, etc). Too much thyroid
hormone is hyperthyroidism; these
people are thin and active. When levels of
TH are too low, it is called
hypothyroidism; these people are
overweight, move slowly, have no energy.
34
• The posterior pituitary is an extension of
the hypothalamus. The cell bodies of
some neurons are in the hypothalamus,
while their axons are within the posterior
pituitary.
• The adrenal gland releases epinephrine
and some norepinephrine. The anterior
pituitary makes 7 hormones that can be
released after a signal by the
hypothalamus.
35
Study Tip to remember the hormones
secreted by the pituitary gland
• “Melons grow and produce through late fall” stands for the hormones
made in the anterior pituitary.
• Melanocyte stimulating hormone (MSH)
• MSH is created by a larger protein precursor, which also makes
ACTH
• Growth Hormone (GH).
• Adrenal corticotropic Hormone (ACTH).
• Prolactin (stimulates the production of breast milk)
• Thyroid stimulating hormone (TSH)
• Luteinizing Hormone (LH)
• Follicle stimulating Hormone (FSH)
36
• For the anterior pituitary to release a hormone, it
needs a hormone from the hypothalamus. If the
hypothalamus releases GH-RH, then the
pituitary will release GH. Some of the cells in the
pituitary are somatotrops, some are corticotrops,
some are thyrotrops. The somatotrops have
receptors only for GH. They only respond to the
one receptor they have. GN-RH is gonadotropic
releasing hormone, which stimulated luteinizing
and follicle stimulating hormones (LH and FSH).
37
• HPT axis is the pathway that goes from the
hypothalamus to the pituitary gland, to the
thyroid.
• HPA axis is the pathway that goes from the
hypothalamus to the pituitary gland, to the
adrenal gland.
• HPG axis is the pathway that that goes from the
hypothalamus to the pituitary gland, to the
gonads.
• The other hormones go straight to their target
38
cells with no intermediate target.
HPT Axis
•
•
•
•
•
•
Neuronal cell body is in hypothalamus, and the axons go to posterior
pituitary. Some synapse onto a blood vessel. Some of the capillaries
continue to another capillary bed (two capillary beds connected by a vessel
is called a portal system). The hypothalamus can release hormones into the
bloodstream directly (humeral mechanism) or release hormones just to the
pituitary (neuronal mechanism). If the signal goes to the second capillary
bed, and if the cells there have a receptor for the hormone, the pituitary will
release its hormone, which will be carried to all cells in body.
Example: Hypothalamus  anterior pituitary  thyroid gland  target cells.
TSH-RH
TSH
TH
NOTE: You have to have enough TH for GH to work; helps prevent
gigantism.
39
• How many controls are there over the thyroid? Three:
TH, TSH, TRH.
• Thyroid hormone goes to all cells of the body, including
the thyroid gland itself, as well as the pituitary and the
hypothalamus. As it does so, the receptors are bound,
inhibiting the release of more hormones. The last
hormone released is the one with the most
significant role in feedback. In this case, the last
hormone released is thyroid hormone. Therefore, the
presence of thyroid hormone is what will stop the
hypothalamus from wanting more. This is negative
feedback, which is what most hormones have.
40
• The one hormone that uses positive
feedback is luteinizing hormone (LH).
When LH is released, it stimulates the
release of more LH, and more LH, until it
reaches a maximum level, then negative
feedback kicks in.
41
What if a gland disobeys the negative feedback?
•
•
•
•
Example: Thyroid gland is impaired by a tumor.
A thyroid tumor might cause it to over-secrete or under-secrete TH.
Under-secreting thyroid tumor: what happens to the other hormone
levels? Start with the problem area (in this case, the thyroid is the place with
the tumor), and then evaluate the other glands.
– TH will be low (hypothyroidism)
– TSH-RH will be high, since only a few hypothalamus receptors are
bound
– TSH levels will be high.
Over-secreting thyroid tumor:
– TH will be high (hyperthyroidism)
– TSH-RH will be low
– TSH levels will be low. This combination tells you the source of the
problem is the thyroid.
42
Example: Pituitary tumor
•
Under-secreting pituitary tumor (Start with the problem area,
the pituitary)
– TSH is low
– TH is low (hypothyroidism)
– TSH-RH is high
• Over-secreting pituitary tumor
– TSH is high
– TH is high (hyperthyroidism)
– TSH-RH is low
•
• NOTE: If the problem is the TSH, we don’t bother injecting TSH, we
just give the hormone that is lacking: Thyroid hormone.
43
Example: Hypothalamic Tumor
• Under-secreting hypothalmic tumor (Start
with the problem area, the pituitary)
– TSH-RH is low
– TSH is low
– TH is low (hypothyroidism)
• Over-secreting hypothalamic tumor
– TSH-RH is high
– TSH is high
– TH is high (hyperthyroidism)
44
• The adrenal cortex has the same cycle as
thyroid hormone; it needs ACTH-RH
(adrenalcorticotropic releasing hormone),
ACTH, CH.
• You always palpate the thyroid during a
physical exam. If it is too large, it is called
a goiter. But you cannot just look at it and
say its hyperthyroidism; it might be
hypothyroidism. You have to measure the
45
hormone levels.
Maintaining homeostasis:
Hypothalamohypophyseal-Thyroid Axis (HPT)
Now let’s use negative feed back to understand the Controls over the
thyroid and how these controls can be disrupted:
Hypothalamus
does not “know”
when to stop
secreting!
Continued
release of TRH
unless it is
signaled to slow
down.
KEY to ARROWS:
Green= stimulates
Red = inhibits
Hypothalamus
Thyrotropin releasing hormone, TRH
Adenohypophysis (AnteriorPituitary)
Thyroid stimulating hormone, TSH
Thyroid
Thyroid hormone, TH
Target Cells = all body cells
46
Controls over the thyroid:
Hypothalamus
Thyrotropin releasing hormone, TRH
Adenohypophysis
Thyroid stimulating hormone, TSH
Thyroid
Thyroid hormone, TH
KEY to ARROWS:
Green= stimulates
Red = inhibits
Target Cells = all body cells
47
Controls over the thyroid:
Hypothalamus
Thyrotropin releasing hormone, TRH
Adenohypophysis
Thyroid stimulating hormone, TSH
Thyroid
Thyroid hormone, TH
KEY to ARROWS:
Green= stimulates
Red = inhibits
Target Cells = all body cells
48
Controls over the thyroid:
Hypothalamus
Thyrotropin releasing hormone, TRH
Adenohypophysis
Thyroid stimulating hormone, TSH
Thyroid
Thyroid hormone, TH
KEY to ARROWS:
Green= stimulates
Red = inhibits
Target Cells = all body cells
49
What happens to hormone levels when…..
…when thyroid function is impaired by either
too much
or
too little activity?
Hypothalamus
TRH
Adenohypophysis
TSH
Thyroid
TH
Target Cells = all body cells
50
What happens to hormone levels when…..
…when ant. Pituitary function is impaired by either
too much
or
too little activity?
Hypothalamus
TRH
Adenohypophysis
TSH
Thyroid
TH
Target Cells = all body cells
51
What happens to hormone levels when…..
…when hypothalamic function is impaired by either
too much
or
too little activity?
Hypothalamus
TRH
Adenohypophysis
TSH
Thyroid
TH
Target Cells = all body cells
52
• The functional unit of the thyroid gland is the
thyroid follicle. The cells making up the
perimeter of the follicle are called follicular
cells. They make and secrete the light purple
liquid within the follicle, called colloid. Colloid is
water, filled with a lot of protein called
thyroglobulin, which is made by the follicular
cells. Since thyroglobulin is a protein, there is a
gene that codes for it. TSH is what stimulates
the follicular cells to make thyroglobulin.
TSH also increases the size of the follicular cells
53
to accommodate all this protein.
• When thyroglobulin is made, it is exocytosed
from the follicular cell and stored outside of the
cell, in the follicle. As it moves across the cell
membrane, a peroxidase enzyme attaches
iodine to the tyrosine (amino acid) portion of
the thyroglobulin. This process is iodination.
After TSH stimulation, the follicular cells drink it
back into the cell, and another enzyme comes
along and chops up the long thyroglobulin
protein into smaller pieces, each with some
iodine on them.
54
• If a segment has two iodines, it is called
T2. If there are 3 iodines attached, it is
called T3 (Triiodothyronine). If it has 4
iodines it is T4 (thyroxine). The T3 and
T4 are then released into the bloodstream.
Those thyroglobulin segments that have
only 1-2 iodines are recycled for parts and
are not released.
55
• T4 is the most abundant form, but it is inert (inactive). T3 has
robust activity in the cell. So, T3 gets used first by the body cells.
T4 takes longer to be ready; one iodine has to drop off. As T3 is
used up, T4 is being converted to more T3. Read page 938 in the
book about what TSH does to the thyroid.
•
• To make thyroid hormone, you need iodine in your body. Iodized salt
has enough to meet this need. Iodine is brought into the follicular
cells, gene expression occurs, thyroglobulin is made. Without
enough iodine in the diet, thyroid hormone cannot be made, no
matter how much TSH is present.
56
Thyroid Gland,
Chap 76
• Thyroid follicles- hollow structures
surrounded by follicular and
parafollicular cells
• Follicular cells produce
Thyroglobulin (TG)- large
glycoprotein made by follicular
cells (~3300 aa of which ~70 are
tyrosine.)
• Building block of TH, chemically
attaching I- to tyrosine.
• In plasma, TH needs a “carrier
molecule” or it will be cleared from
body
Tyrosine: a bulky amino acid
containing a large benzyl ring.
57
Thyroid Hormone Synthesis & Secretion
• Link two tyrosine aa’s
together and add
iodine
• Thyroid hormone
(TH)- controls
metabolic rate and
protein synthesis
– Thyroxine – T4 :
(93%)
– T3:
triiodothyronine
(7%); 4x as potent
• Active form
Figure 76-3 Chemistry of thyroxine and triiodothyronine formation. 58
•TG is booted out of the cell (exocytosis) and stored inside the hollow chamber
of the follicle. “Colloid”
•When follicular cells receive signal to secrete (TSH), they take up TG
(endocytosis), cleave off the TH from TG, and secrete it into blood (exocytosis.)
•Page 938- know what TSH does to the thyroid!
Figure 76-2; Guyton & Hall
PTU blocks the
peroxidase and
organification
process.
Pg 939
59
What are the
“actions” of TH?
Incr GI motility
Incr mental and endocrine
activity
Promotes growth and brain
dvlpmt in fetal life, and early
postnatal life.
Stim fat metab, lipid mobilization
from fat stores
Excites CNS (B-adrenergic
stimulant), muscle activity
Sleep difficulty
Na/K+ ATPase activitythermogenic affect
60
• Know what would happen to the three
hormone levels (TSH, TSH-RH, TH) in the
following conditions:
• Antibodies attacking thyroid gland,
destroying the gland
• Antibodies binding to the TSH receptor,
stimulating it
• Graves Disease
• Hashimoto’s Thyroiditis
61
• The TS ratio is the amount of iodine in
thyroid /iodine in serum. There are 30x
more iodine ions in the thyroid gland than
in the plasma. ATP is used to bring iodine
into cells against its electrical gradient.
62
• A protease is an enzyme that chops up
proteins. In the case of thyroglobulin, the
protease cleaves it into T1 (called MIT), T2
(called DIT), T3, T4, or sometimes it
creates a segment called R-T3, a mirror
image of T3, which is inert, not used. MIT
and DIT are also recycled, not used.
63
• If someone has excess TSH, thyroid will
get larger, called a goiter.
• You can have a goiter with decreased TH
also. The cause of this is PTU (propyltriouracil), which inhibits TH production by
blocking the peroxidase enzyme that joins
the iodine to the tyrosine. It results in low
thyroid hormone levels, and a goiter
develops.
64
• What happens when TSH is released? Every step in the
process of making TH is increased: Follicular cells
become larger, more columnar. Metabolism increases:
increase in O2 use (especially in mitochondria), a large
sodium gradient is outside, and a large K gradient is
inside, requires ATP to keep them from diffusing across
their concentration gradients; this process generates
heat. The NA-K ATP gene is expressed. There are
sympathetic (beta) receptors in the heart that become
stimulated. The heart increases in force of contraction
and rate.
65
• TH also stimulates neurons; the person feels more alert,
observing their environment with more interest. With not
enough TH, they lose interest, become sluggish. When
there is too much TH, they get muscles tremors, liver
cleaves stored glycogen to increase blood glucose
levels, gluconeogenesis increases in the liver, body cells
grow. Remember, you need TH present for GH to work.
TH is also important for brain development in fetal life.
• We can measure hormones in the blood by
radioimmunoassay (RIA) or ELISA (enzyme-linked
immunosorbent assay).
66
Diagnosing the etiology
of hypo/hyperthyroidism
• Methods of measuring
plasma concentration of
hormones:
– RIA
(radioimmunoassay)
– ELISA (enzyme-linked
immunosorbent assay)
• Sample a small amount
of patient’s blood; to lab
• Concentration: picomolar
concentration
67
RIA
• In a dish are antibodies against a hormone we want to
measure. Before adding blood, add the hormone with a
radioactive tag that can be recognized by those
antibodies. It forms a complex; wash away the unreacted
hormone. Then measure the radioactivity that is given
off, this is the saturation point (the starting point). Now
add the patient’s blood sample. If it has a lot of the
hormone that is already attached, it will compete to push
off the radioactive hormone, and the radioactive signal
will drop proportionally. If the patient does not have
much hormone, there is not much decrease in
radioactivity. This is an inverse relationship. The RIA test
is expensive and dangerous, so ELISA is preferred.
68
ELISA
•
•
•
Pregnancy test is an example of an ELISA test.
On the strip are antibodies. If pregnant, a hormone binds to the receptor.
When the strip gets wet, a second set of antibodies move over the
pregnancy hormone. The substrate, when cleaved, precipitates out of
solution; it gives you a color, and a new line appears, turning the negative
into a plus sign. If no hormone is present, there is no second set of
antibodies, the enzyme is not cleaved, no color change.
Is she a little or a lot pregnant? Well, there is no in-between, so is this test
not considered quantitative? Actually, it can be quantitative: Suppose she
had sex only a few hours ago. The test would be negative, since it takes 7
days for zygote to implant into uterus, which is when hormone levels are
high enough for detection. If she is 6 months pregnant, the response time is
faster. Since the response time is faster in the presence of higher hormone
levels, we can quantify the pregnancy also. The parasite chomping into
uterine artery can cause bleeding, seems like a period. She may be
shocked to find out she’s pregnant.
69
Hyperthyroidism
(Most commonly caused by Graves Disease)
• Signs include thinness, eyes that stick out
like a bug (exophthalmoses).
• Graves Disease is a person who has
antibodies against TSI. These antibodies
bind to thyroid gland, tricks it into making
excess TH, while TSH-RH and TSH
levels are decreased. You can also get
hyperthyroidism from over-secreting
tumors.
70
Disorders of the thyroid-- hyperthyroidism
•Graves disease/ TSI
•Tumor (hypothalamic/hypophyseal/thyroid)
Hypothalamus _
TRH
+
Thyrotrope _
Figure 76-8 Patient with exophthalmic
hyperthyroidism. Note protrusion of the eyes and
retraction of the superior eyelids. The basal
metabolic rate was +40. (Courtesy Dr. Leonard
Posey.)
TSI
Draw the disrupted pathways!
TSH
+
+
Thyroid
T3, T4
71
There are two ways to treat this disease
• You can have the thyroid oblated (killed off) by drinking radioactive
iodine; it kills just thyroid tissue. As metabolic rate slows, gains
weight again. They set off Geiger counters for months afterwards.
Then start on artificial thyroxin, need to figure out what their set point
is for normal.
•
• The other way (not so good) is to have the thyroid gland surgically
removed. However, the parathyroid glands are often damaged or
removed during this surgery. They often intentionally leave some
thyroid tissue behind, in hopes of leaving enough parathyroid glands
there. If too many of the parathyroid glands are removed, calcium
levels go down, can go into cardiac arrest. Now the patient has to
have two hormones replaced.
72
Hypothyroidism
This can be caused by
• Hashimoto’s thyroiditis
• Iodide deficiency
• Tumor
• Defective enzyme in thyroid.
Know the difference between cretinism and
congenital hypothyroidism.
73
Disorders of Thyroid
• Hypothyroidism
– Hashimoto’s thyroiditis
– Iodide deficiency
– Tumor (undersecreting)
– Defective thyroid (enzyme
problem)
• Draw the disrupted pathway!
• Goiter?
• Thyromegaly-TSH stimulation
leads to increased number and
size of thyroid cells
• Cretinism- mental defects due
to maternal deficiency
• Myxedema
• Hashimoto’s and idiopathic
hypothyroidism are similar in
symptoms
74
Figure 76-9 Patient with myxedema. (Courtesy Dr. Herbert
Langford.)
Cretinism
Goiter
Cretinism (diminished mental ability)
• This term describes babies whose
MOTHER had the lack of iodine. Baby
now cannot get iodine, and the baby will
have reduced growth and intellectual
ability. Once it is born and gets a healthy
diet, it still won’t go back to normal
because TH is necessary for proper
myelination and synaptic formation.
75
Congenital hypothyroidism
• Congenital hypothyroidism is the term
for a baby whose thyroid gland is not
working correctly, the problem is only with
baby, not with the mom. Congenital
hypothyroidism and cretin babies have
similar symptoms. Child will stay tiny
because GH does not work without TH.
76
Hashimoto’s thyroiditis
• Hashimoto’s thyroiditis is an autoimmune disorder,
where antibodies attack and destroy the thyroid gland,
and TH goes down while TSH-RH and TSH are
elevated. The healthy remaining thyroid tissue will
enlarge.
• Myxedema is non-pitting edema. Touch it, feels solid,
and does not leave a fingerprint when you push on it.
People with Hashimoto’s thyroiditis have depressed
mental and emotional activity, may have psychosis, not
in touch with reality, detached. They gain weight easily,
are tired and sleep a lot.
77
Iodide deficiency
• Iodide deficiency has decreased TH,
other hormones increased.
• Other things that cause hypothyroidism
are defects in any parts of the gene
expression of thyroglobulin in follicular
cells; TH not released in proper amounts.
78
symptoms
Symptom of
Hyperthyroidism
Affected molecule or
system
Symptom of
hypothyroidism
Decreased weight
Increased BMR
Mitochondrial enzymes
Increased weight
Decreased BMR
Heat intolerance
Na/K ATPase
Cold intolerance
Increased heart rate
B1-adrenergic receptor
Decreased heart rate
Irritable
Sympathetic B-adrenergic Sluggish (increased
receptors
somnolence)
Exophthalamos
TSI (thyroid stimulating
immunoglobulin)
__________
Goiter
TSI or TSH
goiter
Myelin
Decreased mental
development
Growth Hormone
Decreased growth
79
A summary of disrupted Hormonal
pathways
Hyperthyroid
(excess T4)
TRH from over-secreting tumor in
hypothalamus-leads to
(increased downstream
hormones)
TSH from over-secreting
tumor in pituitary- leads to
decreased TRH but elevated
TSH and TH
TSI –Graves disease, autoimmune
activator of the TSH receptor- leads
to increased TH, but decreased TRH
and TSH
Hypothyroid
(decreased T4)
Nutritional iodine deficiency (leads to
increased TRH and TSH)
Defective thyroid
•Iodide uptake
•Peroxidase
•Deiodinase
• leads to elevated TRH and TSH
Hashimoto’s Thyroiditis
(autoimmune destruction)
•Leads to Elevated TRH and TSH
80
Adrenal glands
• They are neuronal and hormonal, like the pituitary.
• Both adrenal medulla glands together weigh only one
gram! The adrenal medulla is an extension of the
nervous system. If the chromatin cells there are
detached, they will differentiate into a neuron! The
adrenal cortex suppresses the full development of the
nervous system development of the adrenal medulla.
The adrenal glands release catecholamines, such as
norepinephrine, and especially epinephrine. These
catecholamines are released when the sympathetic
nervous system is activated (“fight or flight”).
81
Epinephrine is antagonistic to insulin
• When you run from a predator, is that when you
want insulin to take glucose from blood? No, you
want to keep it there so the brain can get the
glucose. The brain needs to think of a way to
escape, and thinking burns glucose. Fatty acids
are broken down as another source of ATP.
Heart rate and force increases. Digestion slows,
respiratory passages open, bronchiole dilation
occurs. BP goes up from vasoconstriction in less
needed organs.
82
• The bulk of the adrenal gland is the adrenal cortex. It
has layers, from superficial to deep: “GFR”
• G = Zona glomerulosa: makes aldosterone
• F = Zona fasciculate: makes androgens and
glucocorticoids (cortisol and corticosteroids)
• R = Zona reticularis: makes androgens and
glucocorticoids (cortisol and corticosteroids)
• (Don’t confuse this pneumonic with GFR in the kidney,
which stands for glomerular filtration rate)
83
The Adrenal Glands- chapter 77
•
•
Located on the superior surface of the
kidneys
Two endocrine glands in one (different
embryological origin)
– Adrenal medulla – a knot of
sympathetic nervous tissue
• Chromaffin cells – modified
postganglionic sympathetic
neurons
• Secrete epinephrine (mostly).
• Active in “fight, flight, and
fright” response
• Glycogen broken down to
glucose for ATP production
• Fats broken down to fatty
acids for ATP production
• Heart rate and force increases
– Adrenal cortex – bulk of the
adrenal gland
84
The Adrenal Cortex
• Secretes a variety of
hormones- all are steroids
made from cholesterol and are
grouped into two main classes:
– Glucocorticoids
• Cortisol – secreted in
response to ACTH and
stimulates fat and
protein catabolism and
gluconeogenesis.
– Mineralocorticoids
• Aldosterone Sodium/water
reabsorbed and loss of
potassium
85
Androgens- small amount but still important
• In the Z. glomerulosa, aldosterone (a
mineral corticoid) is released. It targets the
cells of kidney, increases the amount of
salt and water that is reabsorbed. The
other two zonas make glucocorticoids and
androgens. Glucocorticoids are cortisol
and corticosteroids.
86
• Androgens (DHEA; Dehydroepiandrosterone), is a
testosterone-like steroid hormone, but is not the primary
hormone responsible for the male characteristics;
testosterone from the testes does that. However, since
females do not have testes, they are sensitive to
androgens present in their body, and the androgens in
females cause them to have pubic and axillary hair. If
that part of the adrenal cortex hypersecretes androgens,
it won’t impact a male, because the testes makes more
than that already. However, in females, hypersecretion
causes masculinization.
87
• Aldosterone
• The Z. Glomerulosa makes aldosteone, but it does not follow a
typical HPA axis; it is a humeral release mechanism. A few things
trigger it, especially high potassium plasma levels. That signals the
kidneys to reabsorb sodium, and water comes with it. But potassium
is secreted and then excreted. Potassium is secreted by the cells of
nephron, sodium and water are regained, and that increases blood
volume. A2 is angiotensin 2 (studied more in unit 4); there is a blood
plasma protein called angiotensinogen. Any word that ends in –
ogen means they are zymogens, the proteins are released in an
inactive form. When activated, cascade events occur. When the
kidney detects BP is too low, it releases rennin, which cuts
angiotensinogen into its active form. Here is the process:
88
• Angiotensinogen  angiotensin 1, travels
through blood and ends in pulmonary
capillary bed, cells have angiotensin
converting enzyme, cuts A1 into A2,
stimulates adrenal cortex to make more
aldosterone, and hypothalamus to release
ADH. If BP drops, this cascades into
events that lead to water and salt
retention, blood volume and BP goes up.
89
Cholesterol
ACTH
CH3
C
O
K+, A II
Hormone
Pregnenolone
Biosynthesis
HO
CH3
C
O
in the Zona
Progesterone
Glomerulosa
O
CH2OH
O
C
11-Deoxycorticosterone
O
CH2OH
C
O
HO
Corticosterone
O
+
Aldosterone K , A II
Synthase
HO
O
CH3
HC C
O
Aldosterone
Copyright © 2006 by Elsevier, Inc.
O
Aldosterone does
not follow a typical
HPA axis-it’s a
humoral release
mechanism
90
Hypothalamohypophyseal-Adrenal Axis (HPA)
Hypothalamus _
CRH
+
_
Corticotrope
ACTH
+
Adrenal Cortex
Glucocorticoid
s
91
• Potassium and A2 are humeral mech.
• ACTH is released by pituitary, is part of APH pathway.
ACTH is required for adrenal to release CTH,
corticotropic hormone. Need ACTH to get the cholesterol
to be processed into aldosterone. Need it to start the
biochemical pathway, but if you raise ACTH, you do not
get a matching increase in aldosterone; it goes up, but
not proportionally. Aldosterone is a humeral
mechanism.
• The HPA axis is a classic pathway; the same rules apply
as the TH pathway. CRH is released by the
hypothalamus, pituitary releases ACTH, adrenal cortex
92
releases corticoids, effects almost all cells in body.
Increase in glucocorticoids
causes things:
•
•
•
•
•
•
•
Cortisol is called a stress hormone; it does several things:
Cortisol stimulates protein and triglyceride catabolism
Stimulates gluconeogenesis in the liver
Inhibits glucose uptake by the body but not the brain
It elevates blood glucose (diabetogenic effect)
It inhibits non essential functions like reproduction and growth
It suppresses the immune response, Inhibition of inflammation
also
• It is prescribed to suppress inflammation and the immune system.
93
Metabolic Effects of Cortisol
Glycogen
Glucose
Protein
Amino
acids
Glucose-P
Glucose
precursors
Stimulate
Muscle
•
•
•
•
•
•
Inhibit
Liver
Glucose
Free fatty
acids
+
Glycerol
Adipose
tissue
Plasma
Glucose
Free fatty acids
Amino acids
Stimulates protein and triglyceride catabolism
Stimulates “gluconeogenesis” in liver
Inhibition of glucose uptake by body (insulin antagonism) but not by brain.
Elevates blood glucose levels, “diabetogenic effect.” Nervous system
becomes primary user of glucose during stress.
Inhibition of non-essential functions (reproduction; growth)
Cortisol tames immune response
Inhibition of inflammation and immune responses (pharmacologic doses
used to suppress immune system.)
94
• The gene code you got from parents is
different from theirs, but not a lot. But the
expression of your genes can be very
different because of how they lived their
life. How much activity, smoking, and
weight gain has gone on before puberty
will damage stem cells, and can silence or
activate a gene. The children of these
people can have genetic differences
because of this.
95
• Children exposed to severe physical
abuse are more likely to commit suicide
later; their DNA is methylated, causing a
reduced number of glucocorticoid
receptors. They cannot bind cortisol,
cannot deal with stress like other people. If
you don’t eat a lot, your children and
grandchildren will live 30 years longer, and
live healthier lives.
96
• Cortisol (also known as corticosterol and also
known as hydrocortisone)
• The hypothalamus portion of the HPA axis releases
ACTH-RH, pituitary releases ACTH, adrenal gland
releases cortisol. The adrenal gland also can release
androgens, which also follow this classic HPA pathway.
When the HPA axis is over-stimulated because of an
intense need to make cortisol in response to stress,
and if the body cannot keep up with the demand for
cortisol, excess ACTH might be shunted into the
androgen production pathway.
97
• What is “stress” that causes cortisol production? Stress
can be emotional or physical. Examples of physical
stress can range from fighting an infection to just a little
paper cut that needs to remodel tissue. Cortisol tells
tissues to stop using glucose (except brain), but will
mobilize fatty acids to release energy for the other
tissues. It tells the skeletal muscle to start breaking down
actin, myosin, and other proteins to release the free
amino acids into bloodstream. The liver takes in these
free amino acids and fatty acids and converts them into
new glucose molecules that you did not acquire from
your food. Since these are new glucose molecules being
formed, this process is called gluconeogenisis
(“generation of new glucose”). The new glucose
molecules are released back into the blood (blood
glucose levels rise) so the other tissues can have some
98
energy.
• If a person has a lot of cortisol or prednisone in their
body, blood sugar levels rise too much, and sugar spills
out in the urine. They have symptoms of diabetes,
although that is not their disease. You have some
cortisol in you now to help maintain blood glucose
levels between meals, and glucocorticoids stimulate
smooth muscle in the vasculature to maintain BP.
• In high doses only, prednisone may be given for
asthma because it suppresses smooth muscle from
constricting, and bronchioles cannot close up. What
would you predict their hormone levels to be?
99
• Makes you hungry to be on this med
(prednisone), hard time sleeping because brain
is stimulated. Stop to fast, like Addison’s
disease. Cant maintain bp, blood glucose drops,
can go to hospital. A person on high dose for 1
or more weeks must be tapered off. There are
two ways to use them: high dose, short duration,
and they don’t wean off, can stop cold turkey.
Use them for longer, need to wean off.
100
• Hypothalamus will lower ACTH-RH, pituitary will lower ACTH, and
endogenous levels of CTH (cortisol) from their own adrenal gland
will be low. The person’s own HPA axis will be suppressed. You
cannot suddenly stop the medicine because it will cause a crash; the
body’s own ACTH and CTH levels are not high enough to maintain
the blood pressure and blood glucose levels (like having Addison’s
disease). Being on prednisone makes you hungry, and it stimulates
the brain, so you have a hard time sleeping. A person on high dose
for 1 or more weeks must be tapered off. There are two ways to use
pharmaceutical glucocorticoids: high dose, short duration (don’t
need to taper off the meds, can stop cold turkey), or use them for
longer duration, and they will need to taper off.
101
Pathophysiology of the Adrenal Gland
Deficiencies
• Primary Adrenal Insufficiency:
Addison’s Disease
– primary hypoadrenalism; entire
adrenal gland is destroyed due
to atrophy or autoimmune
disorder
– Tuberculosis –disease attacks
adrenal gland
– ACTH is increased (map the
pathway!)
• Secondary adrenal insufficiency
– deficiency of ACTH
– Rapid withdrawal of
pharmacologic doses of cortisol
• Signs/symptoms: Water/salt
imbalance, plasma volume
depletion, low blood glucose,
pigmentation, Addisonian crisis
http://www-clinpharm.medschl.cam.ac.uk/pages/teaching/images/addisons.jpg
DRAW THE PATHWAYS!
102
ADDISON’S DISEASE
• Also called Primary Adrenal Insufficiency and
hypoadrenalism; mainly see effects in the hands, fingers,
and gums. Addison’s disease may be caused by
anything that disturbs the production of adrenal
hormones (for some reason, Tuberculosis attacks the
adrenal glands as well as the lungs, and can cause
hypoadrenalism). In Addison’s disease, the adrenal
cortex does not respond to HPA orders. Cortisol (CTH)
levels are low, but pituitary ACTH and hypothalamus
ACTH-RH hormones are high.
103
• ACTH is a peptide (protein) hormone,
synthesized from a larger protein called POM-C
(Pro-opiomelanocortin). From the large POM-C
protein, you cut out one segment, called ACTH,
and another segment called MSH (melanocyte
simulating hormone). When the ACTH levels
increase but you still need more, PROM-C
cleavage continues to occur, and more MSH is
generated at the same time. When MSH is in
excess, you get darker skin (hyperpigmentation).
104
• Symptoms of Addison’s disease are
decreased glucose levels, a drop in
blood pressure from water and salt
imbalance, and darkening of the skin.
Aldosterone is also not being made, so
kidneys cannot absorb salt and water as
well, blood volume and pressure
decreases even more.
105
• In Secondary Adrenal Insufficiency, the
problem is in pituitary; it is not secreting enough
ACTH, maybe because of a tumor. Cortisol
levels drop, but hypothamus ACTH-RH
increases. A person can also get secondary
hypoadrenalism from rapid withdrawal of cortisol
meds. Symptoms are the same as for primary
adrenal insufficiency, except blood tests show
that pituitary ACTH levels are low, adrenal
hormones are low, and hypothalamus ACTHRH is high.
106
CUSHING’S DISEASE
• Excess ACTH caused only by a pituitary tumor.
Patient has excess cortisone, high blood
pressure, high blood glucose, and too much
aldosterone is produced. More salt and water is
reabsorbed by the kidney, so the blood volume
increases. In this disorder, the hypothalamus
(ACTH-RH) levels are low, the other hormone
levels (ACTH, cortisol, androgens, and
aldosterone) are high.
107
CUSHING’S SYNDROME
(Andrenogenital Syndrome)
• Excess cortisol secretion, but not caused
by the pituitary gland. It could be caused
by primary hyperadrenalism, an adrenal
tumor, or even by a tumor in the lungs that
releases ACTH (ectopic ACTH producing
tumor). In this disease, all adrenal
cortical hormones (cortisol, androgens,
and aldosterone) are elevated, but
ACTH-RH and ACTH levels are low.
108
Symptoms of Cushing’s Disease and Cushing’s Syndrome
• Fat deposition around waist, scapula (buffalo hump),
and “moon” shaped face. There is muscle loss and
weakness (cortisol tells muscles to break down), thin
skin with striae, (High levels of cortisol leads to
destruction of collagen, get thin and striae on skin),
hyperglycemia, immune suppression. Excessive
amounts of adrenal stimulation causes release of male
steroids, causing male secondary characteristics, but
only in females. Adult onset disease in females
causes masculinization, including facial hair, thicker
jaw and skull.
109
https://courses.stu.qmul.ac.uk/smd/kb/resources/endocrinologyresource/syndromes/cushingssynd.htm
Excessive Adrenal Hormones
Cushing’s Disease- pituitary tumor
(excess ACTCH)

Cushing’s Syndrome
•Ectopic ACTH producing tumor
(lungs) Glucocorticoid therapy
•Iatrogenic
•Primary hyperadrenalism -Functioning
adrenal tumor-, all adrenocortical
hormones elevated; adrenogenital
syndrome
Signs/symptoms: buffalo hump, moon
face, muscle loss/weakness, thin skin with
striae, hyperglycemia, immune suppression

110
• Congenital adrenal hyperplasia (CAH) in a female
fetus causes the clitoris to enlarge and the labia major
fuse into a scrotal sac. These babies have a mutation in
a gene, some enzyme is not expressed which is required
to convert cholesterol into corticosteroids, so cholesterol
is shunted to the pathway that is not compromised:
androgen production. Boys are not affected; girls need a
surgery and cortisol for life, will be fine. The most
common gene mutation is 21 beta or 11 beta
hydroxylase to covert progesterone to corticosterone. If
the presence of ACTH is driving the pathway, and it is
blocked at this enzyme, the ACTH can only be used to
make androgens.
111
CAH- Excessive and Deficient?
•
Congenital Adrenal Hyperplasia (CAH)
– Autosomal recessive trait
(congenital)
– Deficiency of any of the five enzymes
necessary for cortisol production.
– Increased ACTH (leads to adrenal
hyperplasia) MAP IT!
– Leads to overstimulation of adrenal
androgen pathways.
– Mineralcorticoids may be excessive
or deficient (depends on enzyme
affected).
– Males seldom diagnosed at birth,
females have virilization (enlarged
clitoris, fused labia, etc).
– With treatment, surgery, sex
characteristics and fertility is normal
http://www.dshs.state.tx.us/newborn/cah2.shtm
21  - Hydroxylase deficiency
11  - Hydroxylase deficiency
112
Hormone Biosynthesis in the
Zona Fasiculata & Reticularis
CH3
Cholesterol
ACTH
HO
3-Hydroxysteroid
dehydrogenase
C
O
CH3
17a-Hydroxylase
(P450 c17)
Pregnenolone
C
O
OH
17-Hydroxypregnenolone
HO
CH3
CH3
C O
C O
OH
O
17, 20 Lyase
(P450 c17)
HO
Dehydroepiandrosterone
O
O
O
21-Hydroxylase
(P450 c21)
Progesterone
17-Hydroxyprogesterone
O
CH2OH
CH2OH
C
C
O
11-Deoxycorticosterone
O
11-Hydroxylase
(P450 c11)
CH2OH
CH2OH
C
O
HO
HO
O
Corticosterone
O
OH
11-Deoxycortisol
O
C
Androstenedione
O
O
OH
Cortisol
113
STUDY TIP
• What hormones are antagonistic to
insulin?
– GH
– Cortisol
– Epinephrine
114
GROWTH HORMONE
(SOMATOTROPIN)
• GH needs TH to be present. GH stimulates all cells to
increase protein synthesis, fat utilization, and
gluconeogenisis, but there is a decline in body usage of
glucose as energy. The person is diabetogenic,
gigantism is the result of excess GH during pre-puberty
and acromegaly is the result of excess GH after growth
plates closed. The genetic determination of a person’s
height has multiple genes involved, so parents might be
tall and have smaller children. There are no rules to
predict it. A child may also be small due to a defect in the
placenta, blocking nutrients during development.
115
Growth Hormone- somatotropin
Chapter 75
• Increased protein
synthesis
• Increased fat utilization
• Increased
gluconeogenesis but
decline in body usage of
glucose as energy
• Diabetogenic
• Excess leads to
gigantism during
prepuberty and
acromegaly after growth
plates are closed
116
PARATHYROID GLANDS
• There are several of these glands, embedded in the
thyroid gland on the posterior surface. The parathyroid
glands are the ones that are the most responsible for
maintaining blood calcium levels. They accomplish
this by releasing parathyroid hormone, which
stimulates osteoclasts to chew away bone, releasing
the bone’s calcium into the bloodstream. The
antagonist of parathyroid hormone is calcitonin,
which is produced in the thyroid gland, and stimulates
osteoblasts to take calcium from the blood and deposit it
in bone. Parathyroid levels are released by a humeral
mechanism. If blood calcium levels are low, parathyroid
hormone is released. If blood calcium levels are high,
parathyroid levels are low.
117
• There are three ways that the
parathyroid gland raises blood calcium
levels
• Stimulates osteoclasts to move bone
calcium into the bloodstream
• Stimulates the intestines to absorb more
calcium from diet
• Stimulates the kidneys to stop excreting
calcium
118
Hormonal Control of Calcium Metabolismchapter 79
PTH and Vit D Actions
• Bone
–  resorption (  osteoclasts)
• Kidney
–  Ca2+ reabsorption
• Intestine
–  Ca2+ absorption
Figure 79-9;
Guyton & Hall
Figure 51-10; Boron & Boulpaep
Osteoclast
Lysosome
Osteoblasts
Acid secretion
Calcitonin?
Osteocytes
119