Download THE ENDOCRINE SYSTEM

Endocrine System notes
Dr. Shaffer’s Human A&P 2
Page 1 of 7
THE ENDOCRINE SYSTEM
The endocrine system controls the functioning of our bodies. So does the nervous system. The
two systems work in very different ways and they interact with each other. The two systems are
sometimes referred to together as the neuroendocrine system. Hormones are chemical
messengers that are released into the blood where they are transported to their targets throughout
the body. The nervous system activates muscles and glands by means of an electrical signal (an
action potential). The hormones released by the endocrine system affect the metabolism of their
target cells. Responses to endocrine control are usually slower, but more prolonged than
responses to nervous input.
Endocrine glands are ductless glands. They release their hormones directly into the
blood. We will be looking at the following glands, their hormones and functions of their
hormones:
Pituitary Gland
Thyroid Gland
Parathyroid Glands
Adrenal Glands
Pancreas
The Gonads
Pineal Gland
Thymus
There are two type of hormones, the water soluble amino acid based hormones and the lipid
soluble steroids. Most hormones are amino acid based hormones. They can range from simple
modified amino acids to polypeptides to proteins.
The remainder are steroids, which are synthesized from cholesterol. Gonadal hormones
and adrenocortical hormones are the only steroid ones.
Hormones circulate through out the body via the blood, contacting just about all cells.
The "target" cells for a particular hormone have receptors, either on the cell membrane, or the
case of lipid soluble hormones that can pass through the membrane, inside the cell. Only the
cells that have the special receptors for that hormone will respond to exposure.
Hormone-receptor binding triggers the target cell to do what its supposed to. The extent
of target cell activation is affected by: levels of hormone in the blood, the amount of receptors
for that hormone, and the affinity of the receptor for the hormone.
Target cells may form more receptors in response to exposure to a hormone (called “upregulation”) or they may lose receptors in response to prolonged exposure (called “downregulation”).
Hormones work by increasing or decreasing the rates at which target cells to what they
do. So the effect of a hormone is directly related to the target cell, and different target cells may
have different responses to the same hormone. Typically, hormones cause one or more of the
following:
Changes in cell membrane permeability
Synthesis of proteins within a cell
Enzyme activation or deactivation
Induction of secretory activity
Stimulation of mitosis
Endocrine System notes
Dr. Shaffer’s Human A&P 2
Page 2 of 7
So the hormone binds to the receptor, so what? How does that do anything? There are two
major mechanisms, second-messenger mechanisms and direct gene activation, by which the
hormone activates the target cell.
Direct Gene Activation. Steroid hormones pass through plasma membrane (they’re lipid
soluble) and attach to receptor molecules that are inside the cell. This combination is now an
activated "hormone-receptor complex" which binds to the chromatin (on another receptor site).
This "turns on" the specific gene, that is, it initiates the process of transcription (which makes
mRNA which is the beginning of protein synthesis). The synthesized protein could be anything.
The point is, the presence of the hormone is what got its production started.
Second Messenger Systems are called that because the hormone (the 1st messenger)
doesn't enter the cell (too big, usually) but initiates production of a chemical messenger within
the cell (second messenger). A molecule known as "cyclic AMP" is a good example of a second
messenger, so we'll talk about it.
• Cyclic AMP does something inside the cell. It does a lot, but we'll skip that for now.
Levels of cyclic AMP in the cell are what matter. What happens is this:
• The hormone binds to a receptor protein imbedded in the cell membrane.
• A "G protein" is activated by this and detaches from the receptor protein. The "G
protein" acts as a catalyst.
• Whenever it finds an Adenylate Cyclase molecule embedded in the membrane it "tells"
the adenylate cyclase molecule to make a cyclic AMP molecule from an ATP molecule.
The hormone is the first "messenger". Cyclic AMP is the "second messenger". The G protein is
just called an intermediate.
(seems like messenger #2 to me....)
Not all G proteins are stimulatory. Some (resulting from different hormone-receptor
combinations) can be inhibitory. In this way cytoplasmic levels of cyclic AMP can be adjusted
by pairs of antagonistic hormones.
So what about this cyclic AMP? It diffuses throughout the cytoplasm of the cell,
activating enzymes called protein kinases. There can be many different protein kinases in a cell.
Protein kinases activate (or deactivate) all kinds of enzymes by phosphorylating them, that is
they add phosphates to them.
This whole business is referred to as a "cascade" effect: One hormone molecule can set a
G protein on its way to hooking up with many Adenylate Cyclases. These make many cyclic
AMPs which go off and activate a whole bunch of different protein kinases which affect all kinds
of cellular activity.
The concentration of hormones in the blood, or levels of hormones, reflect the rate of
release and speed of inactivation of the hormone. Some are inactivated by destructive enzymes
at the target cell; most are removed from the blood by the kidneys and liver.
The "half-life" of a hormone is a term used to describe its persistence in the blood stream.
Usually they range from seconds to 30 minutes. Even though the hormone may be just about
gone from the blood, some hormones have effects that last hours after blood levels are very low.
Hormones are released by glands when the glands have been stimulated. This stimulation can be
humoral, neural, or hormonal. This is on p 477 in your book under “control sources”. (p512 in
the old book.)
Endocrine System notes
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Dr. Shaffer’s Human A&P 2
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Humoral stimuli - response to blood levels of ions or nutrients Ex: Ca++ and the release
of PTH.
Neural Stimuli - nerve fibers stimulate hormone release from the gland. Ex: Sympathetic
simulation of the adrenal medulla causes epinephrine release during stress.
Hormonal stimuli - hormones from one gland trigger a different gland to release
hormones.
The nervous system can modify much of this activity via the hypothalamus.
THE GLANDS
Pituitary Gland or Hypophysis
• secretes many major hormones
• There are 2 lobes. The posterior lobe, or Neurohypophysis, is made up of neuroglia and nerve
fibers. It serves as a hormone storage area of hormones from the hypothalamus. The anterior
lobe, or Adenohypophysis, is truly glandular and releases many hormones.
The neurohypophysis is part of the brain. It’s derived from (during embryonic
development) the hypothalamus. Axons of neurons in hypothalamus form the hypothalamichypophyseal tract, which runs through the infundibulum to the neurohypophysis. These neurons
produce the neurohormones, Oxytocin and ADH. "Firing" these neurons releases the hormone
into the blood stream (via a nearby capillary bed). This would be an example of a neuronal
stimulus.
The adenohypophysis has a different derivation (Rathke's pouch. C’mon shout it with
me- RATHKE’S POUCH!!!). There's no direct neural connection between the adenohypophysis
and the Hypothalamus. There is a vascular connection via the hypophyseal portal system. The
hypothalamus can send releasing and inhibiting hormones to the adenohypophysis through this
little system of blood vessels. These regulate the secretory activities of the cells of the
adenohypophysis.
Hormones of the Adenohypophysis
• There are six
• They are released when the appropriate chemical cue comes down from the hypothalamus.
• The releasers & inhibitors from the hypothalamus are important. They regulate the secretory
activity of the adenohypophysis; there’s no storage in the adenohypophysis.
• 4 of the 6 are called tropins, or tropic hormones, this means they regulate the activity of other
endocrine glands.
• 2 of them have non-endocrine targets (so they’re not tropins).
A. Growth hormone (GH)
Produced by somatotropic cells (GH is also called somatotropin)
GH stimulates most body cells to increase in size. Main targets are bones (epiphyseal plate), and
skeletal muscles (they increase in mass).
GH secretion is regulated by two secretions of hypothalamus:
GHRH - Growth hormone releasing hormone.
Endocrine System notes
Dr. Shaffer’s Human A&P 2
Page 4 of 7
GHIH - Growth hormone inhibiting hormone
Feedback mechanisms can be at pituitary or hypothalamic level. That is, increased GH can
trigger GHIH release from hypothalamus or feedback directly to pituitary to decrease production
of GH.
What does it do?
• GH stimulates enlargement and division of cells
• GH enhances the movement of Amino Acids through membranes thereby increasing
protein synthesis
• GH decreases cellular carbohydrate use
• GH increases cellular fat use
• GH is released when bloods sugar is low
How?
• It acts directly on the cell to cause production of Insulin-Like Growth Factors (IGFs)
• Liver, skeletal muscle, cartilage, bone (others) secrete IGFs
• IGFs act locally (paracrine or autocrine) or enter blood
Other facts:
The highest blood levels are found at night.
GH levels peak at adolescence and decline w/age.
Stress, nutrition, etc. can effect GH release.
GHIH (also called somatostatin) from the hypothalamus, also blocks the release of other pituitary
hormones.
Blood glucose level is a major regulator of GHRH and GHIH production and therefore GH
levels.
See figure which I have posted separately as GH figure.pdf
B. Thyroid stimulating hormone (TSH) A.K.A. Thyrotropin
produced by Thyrotropes when they are stimulated by TRH (thyrotropin releasing hormone)
from the hypothalamus
stimulates development of thyroid gland
stimulates activity of thyroid gland
TSH production triggered by TRH, thyrotropin releasing hormone from hypothalamus.
Decreasing thyroid hormones in blood are detected by hypothalamus and pituitary, which leads
to an increase in TRH from hypothalamus & an increase in TSH release from adenohypophysis.
High levels of Iodine in the blood reduce the production of TRH.
C. Adrenocorticotropic Hormone (ACTH)
Secreted by corticotropes (ACTH is also known as corticotropin).
ACTH stimulates adrenal cortex to release corticosteroids. (Aldosterone, angiotensin, cortisol,
sex hormones).
The hypothalamus regulates ACTH production by the pituitary via Corticotropin Releasing
Hormone (CRH).
Endocrine System notes
Dr. Shaffer’s Human A&P 2
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High levels of corticosteroids block secretion of CRH.
ACTH release also has diurnal pattern, peaking in the morning.
"stressors" trigger CRH release.
D. Gonadotropins (these count as 2 hormones, if you’re trying to figure out how we get six
anterior pituitary hormones)
Follicle stimulating hormone FSH
Luteinizing hormone LH
Secreted by gonadotropes.
Gonadotropins regulate functions of the gonads including sperm or egg production and
production of gonadal hormones.
Gonadotropins are not present in the blood before puberty.
GnRH, gonadotropin releasing hormone from hypothalamus triggers gonadotropin release.
E. Prolactin PRL
Secreted by mammotropes ( also called lactotropes)
Stimulates milk production
Controlled by PRH (prolactin releasing hormone) and PIH (prolactin inhibiting hormone) from
hypothalamus.
Males are largely under the influence of PIH. In women the levels of prolactin cycle along
w/blood estrogen levels.
Hormones of the Neurohypophysis ADH and Oxytocin
Oxytocin – Milk let-down, uterine contractions
ADH Antidiuretic Hormone – decreases urine production (i.e. keeps fluids in circulatory
system), increases blood pressure by constriction of arterioles. Osmoreceptors, specialized
neurons in the hypothalamus, detect levels of dissolved solutes in the blood.
That’s it for the pituitary gland . . .
Thyroid Gland
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It’s the largest gland
It produces two types of hormones, thyroid hormones (T3 & T4) and calcitonin
T3 and T4 are produced by follicle cells; calcitonin is produced by C-cells
Thyroid hormones stimulate enzymes which are involved in glucose oxidation, increasing
metabolic rates of cells. Also important are their role in blood pressure regulation, tissue
development, and reproductive capability.
• Decreasing levels of Thyroxine (T4) trigger TSH release from adenohypophysis. Increasing
levels of T3 shut off incoming TRH (to adenohypophysis from hypothalamus).
• When the body demands more energy, for example when exposed to cold for long periods, the
hypothalamus releases TRH, which triggers TSH, which increases circulating levels of TH,
which raises body metabolism and thereby increases heat production.
• These things inhibit TSH release
Endocrine System notes
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Dr. Shaffer’s Human A&P 2
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somatostatin (GHIH)
sex hormones & glucocorticoids
high blood iodine.
Calcitonin is also produced by the thyroid gland. Calcitonin lowers blood calcium levels by
1) inhibiting osteoclast activity
2) stimulating Ca++ uptake in bone matrix
* The presence of Ca++ ions is the trigger so this is an example of a humoral stimulus.
Parathyroid Glands
• Located on the thyroid gland
• Secrete PTH (parathyroid hormone)
• PTH is most important hormone controlling calcium balance.
• There are 3 targets of PTH
1. skeleton, where it stimulates osteoclasts and inhibits osteoblasts.
2. kidneys, where it enhances reabsorption of calcium, and activates vitamin D.
3. intestine, where it increases calcium absorption by the mucosal cells that line the
intestine, with the help of calcitriol (which is the activated vitamin D).
Adrenal Glands
• Located on top of the kidneys, they are also known as suprarenal glands.
• Consist of two parts:
The inner part, the adrenal medulla, is nervous tissue, and is part of the sympathetic
nervous system.
The outer part, the adrenal cortex, produces entirely different hormones.
• Both parts, and the hormones they produce, are important in stress situations.
Adrenal Cortex
The hormones of the adrenal cortex are called corticosteroids. There are 3 groups,
mineralocorticoids, glucocorticoids, and gonadocorticoids.
Mineralocorticoids - Regulate electrolytes, mostly Na and K. Aldosterone is the most common
(95% of all mineralocorticoids produced) and its used in Na regulation. A number of factors
affect aldosterone secretion. Secretion is stimulated by increased blood levels of potassium,
decreased levels of sodium, and decreasing blood volume and pressure. (Do you see how this
works? Increased sodium in the blood will cause water to leave the cells and interstitial fluids
and enter the blood, thereby increasing blood volume and blood pressure). The opposite
conditions are inhibitory.
Glucocorticoids - Keep blood sugar levels constant despite intermittent food intake. Crisis
situations (trauma, infection) stimulate higher output of glucocorticoids.
• Cortisol (hydrocortisone) is the main one
Endocrine System notes
Dr. Shaffer’s Human A&P 2
Page 7 of 7
• Regulation of cortisol is simple negative feedback. High levels of cortisol influence both the
hypothalamus, shutting down CRH release, and the adenohypophysis, shutting down ACTH
release.
Gonadocorticoids - These are the same sex hormones, androgens and some estrogens, that are
produced in much larger amounts by the gonads. They contribute to the onset of puberty.
• ACTH stimulates their release. No apparent feedback system.
Adrenal Medulla
• Secretes epinephrine and norepinephrine, known together as catecholamines.
• Sympathetic stimulation of the adrenal medulla causes the release of the catecholamines which
enhance and prolong the flight-or-fight response.
Pancreas
• It’s considered a “mixed” gland. It has exocrine parts that produce digestive enzymes. And
endocrine parts that produce the hormones insulin, glucagon, somatostatin, and pancreatic
polypeptide.
Glucagon is called a hyperglycemic agent because it causes the release of glucose into the
blood. Liver is the target of glucagon (obviously - this is where the glycogen is stored).
This is an example of humoral stimulation; blood sugar is the trigger. Release of
glucagon is inhibited by high blood sugar & by the hormone somatostatin.
Insulin is called a hypoglycemic agent. Its main effect is to lower blood sugar levels by
enhancing transport of glucose into body cells. Elevated blood sugar stimulates the
release of insulin. Decreasing levels suppress insulin release. This is an another
example of humoral control. Other hormones, such as epinephrine, GH, and
glucocorticoids, that circulate in response to low blood sugar (and work to elevate it) act
as hormonal controls and increase insulin production.
Read and be responsible for:
The gonads, the pineal gland, the thymus, and other endocrine structures on pp 498 – 500, pp
533-535 in the old book.