ENDOCRINE SYSTEM

Day 1
Somewhere along the way, we talked about different types of tissue, and we talked about
epithelial tissue; we said that there is glandular and nonglandular epithelial tissue. For glandular
epithelial tissue, there were two types of glands, exocrine glands and endocrine glands. We said
that exocrine glands had ducts and secretion was carried through the duct to some limited
physical location and that the secretion had a direct effect in that location. In endocrine glands,
the secretion is released from the cell into interstitial space, which is the fluid around the cell,
and then the secretion was picked up by the circulatory system and delivered to the entire body;
we said that the secretion had no immediate or direct effect, that the secretion has to bind with a
receptor and that the receptor determines the effect. Those types of secretions are called
hormones, so the secretions made by the endocrine system are hormones; they do not act locally
nor directly, but instead are carried by the bloodstream and must bind with receptors, and the
receptor determines the effect, not the hormone. Today we are going to talk about the endocrine
system and the hormones that the glands make.
Let us quickly talk about hormones in general, then we will talk about the glands
themselves. Hormones can either be peptides made out of aminoacids, or they can be lipids
primarily made out of cholesterol, called steroid hormones. There are two basic kinds of
hormones: peptide hormones and steroid hormones. These hormones bind with receptors;
peptides cannot pass through the plasma membrane of a cell, they have to bind with a receptor on
the surface of the cell, and then the receptor activates some type of effector mechanism that then
produces a second messenger, an intracellular version of the extracellular signal. You can think
of the hormone as a primary message and it produces another internal signal, and it is the second

messenger within the cell that determines the effect. The hormone itself does not have any direct
effect, it binds with a receptor, the receptor activates some type of effector mechanism that
produces an intracellular chemical, and that intracellular chemical acts on the cell and affects the
activity of the cell. Because the hormone is free out there in circulation, there are lots of
naturally occurring enzymes within our bloodstream that destroy hormones, so the peptide
hormones have very short effects because they are eliminated very quickly from the bloodstream,
so peptide hormones also have very rapid effects, but the effects do not last for very long. Think
about something like epinephrine, it has a very short but quick effect.
The other type of receptor is actually inside the nucleus and the actual DNA acts as the
receptor, the physical confirmation of the folding and the bending of the DNA acts the receptor
site. So the lipid based hormones pass through the plasma membrane and enter into the
cytoplasm; even though the nuclear membrane is lipid based also and they could simply pass
through the nuclear membrane, it is a big place in there and to actually get through the cytoplasm
into the nucleus usually involves what is called a chaperone molecule; so the hormone moves
across the plasma membrane, binds with the chaperone, and the chaperone delivers the hormone
to the specific gene sequence that the hormone is going to control. Steroid based hormones
effects are not seen very quickly because they are going to alter gene expression, but the effects
have long duration. Estrogen, testosterone, progesterone, aldosterone, they are all steroid based
hormones that very long lasting effects. The lipid based hormones do not make a second
message because the actual hormone itself can get into the cell and into the nucleus, so it does
not need to make a second message.
If a hormone is simply released into the bloodstream, how can the hormone be specific?
Why does it not just have some generalized effect on the body? Why is there specificity in the

responding of hormones? A couple different variables contribute to specificity. First, and

probably most importantly, is where is the receptor. Receptors are not expressed homogenously
throughout the entire body; receptors for say oxytocin are not on all body cells, they are
expressed in certain body cells. Oxytocin causes the let down reflex and also the contraction of
the myometrium of the uterus. Oxytocin does not cause smooth muscle contraction of the
jejunum, it causes smooth muscle contraction in the uterus, and the only reason for that is
because that is where oxytocin receptors are expressed, when they are expressed in the terminal
states of pregnancy or lactation. The effects depend on where the receptors are. Some
substances like epinephrine have multiple effects, it can affect the heart, the glands, the muscles
in the blood vessels. There are also different types of receptors; so where the receptors are, what
kind of receptor it is, and also in some circumstances, the concentration of the hormone. If you
have a low level of testosterone that creates a certain collection of effects, if you are given an
individual a very high level of testosterone, it actually has some pretty dramatic behavioral
effects; it induces predatorial and territorial aggression in animals, it causes those gym buffs
some roid rage, people get pretty aggressive when they have high levels of testosterone.
Specificity depends on location, receptor type, and hormone concentration. Receptors also differ
in their affinity, their ability to bind to hormones.
What makes a hormone released? They are not just released periodically, they are
released to control ongoing physiological activities, but they are done so in a very exacting way,
so we need stimuli that cause their release. There are three basic stimuli that cause hormonal
release: neural stimuli, humoral stimuli, and hormonal stimuli. Some hormones are made by
neurons and are released when those neurons are activated, like oxytocin and ADH, they are
synthesized in neurons and released when those neurons are activated. There are humoral

mechanisms; some hormones are released in response to changing levels of nutrients or minerals.
Insulin, glucagon, both of those hormones are released in response to changing blood glucose.
Calcitonin, PTH, those two hormones are released in response to changing calcium levels. The
most common stimulus, the one that is responsible for most hormones released, are other
hormones; one hormone controlling a second hormone. For example, the hypothalamus
produces a hormone called CRH, cortisol releasing hormone, which acts on the anterior pituitary
which produces ACTH, which acts on the adrenal cortex that releases cortisol.
The next thing we want to begin talking about are the endocrine glands themselves. If
you have had any academic exposure to the endocrine system, it was probably said that the
pituitary gland was the most important gland, even referred the master gland, because it produces
so many substances that control so many other endocrine glands. The reality is that pituitary is
controlled by the brain, by the hypothalamus of the brain. If this is your hypothalamus, the
hypothalamus is physically connected via a stalk of tissue extending out of the brain called the
infundibular, sometimes call the hypothesis. The pituitary has two regions, a posterior and
anterior part. The hypothalamus directly controls the posterior pituitary; there are neurons within
the hypothalamus that extend projections down, called axons, and those axons terminate in the
posterior pituitary. The neurons synthesize neuropeptides and transport them down the axon and
store them at the end of the axon in what is called the axon terminal in little secretory vesicles.
Remember when we talked about gene expression, and that the gene is transcribed and then
translated, and then the gene product is packaged in a secretory vesicle which migrates up and
fuses with the plasma membrane, in this case, the secretory vesicle migrates down the entire
axon and gets stored in the terminal. There are two different types of neurons that make two
different substances; one of the pituitary substances is ADH and the other is oxytocin. There are

two different hormones made in the hypothalamus and stored in these axon terminals. When the
neurons are activated, the hormones are released, picked up by the bloodstream, and delivered
throughout the entire body. Yesterday we talked about what ADH does, it acts on the kidney
tubule and causes water to be reabsorbed out of the distal convoluted tubule, increasing blood
volume and ultimately increasing blood pressure. ADH is released in response to decreasing
blood pressure. The other hormone is oxytocin; the primary effect of oxytocin is called the let
down reflex. Most individuals who know of oxytocin might know of its role in childbirth:
oxytocin causes the myometrium of the uterus to contract, but you could give birth without
oxytocin from the posterior pituitary, it is only released in the later stages of childbirth. The
earlier stages of childbirth are unrelated to oxytocin, it does not start childbirth, it is in stage 2
labor, but we will say that it causes contraction of the myometrium, myo meaning muscle,
metrium is a layer of the uterus, which essentially participates in delivering the fetus during
childbirth. But the primary effect of oxytocin is the let down reflex: the mammary glands are
organized in what are called the lobules of the breast, these are exocrine glands so they have
ducts, all of the ducts come together and form a single duct that exists out through the center of
the nipple. Overriding all of the ducts is a thin layer of specialized epithelial cells that has actin
underneath their plasma membrane called myoepithelial cells. These are the mammary glands,
covered by the myoepithelial, which is a thin layer of epithelial cells that acts like a muscle.
When oxytocin is present, the myoepithelial cells compress the underlying mammary gland,
pressurizing the fluid, pushing it into the mammary ducts, and then causing it to exit out through
the nipple. It is called the let down reflex because of the physical sensation that the woman
experiences as the milk leaves the mammary gland and enters the duct, she can feel it let down.
Day 2

Last class we finished talking about the posterior pituitary, we talked about oxytocin and
ADH. Now let us talk about the anterior pituitary and the hormones it makes, and then we will
talk about the other endocrine glands.
You might remember we had said that there are two pituitaries. For the posterior
pituitary, the neurons that make the secretions extend their axons down and then these secretions
are released and travel through the bloodstream, and we can consider this a direct connection,
though it is not mechanically/physically direct, it is functionally direct because the hypothalamus
produces and releases the hormones. In the anterior pituitary, the hypothalamus has indirect
control, it does not make the hormones that the anterior pituitary releases, but it controls them.
The hypothalamus makes what are called releasing factors; in this case there are neurons that
make hormonesthese are hormones do not travel very far, but they are still hormones.
Remember, by definition a hormone is something that is made by a secretory cell, released into
interstitial space, picked up by the circulatory system to affect some distant target; in this case
the distance is about half a centimeter, but it is still at a cellular level pretty far away. Anyway,
the neurons of the hypothalamus makes releasing and inhibiting factors that are released from
those neurons into a capillary bed called the primary plexus, and then there is a little vascular
shunt that is called a hypophyseal portal vein, and that carries these hormones made by the
hypothalamus down to the anterior pituitary.
In the anterior pituitary, there is another capillary bed called the secondary plexus, and
this then releases those factors made by the hypothalamus into the anterior pituitary. These are
not the same hormones that are made by the anterior pituitary, these are hormones that control
the anterior pituitary; for example, the hypothalamus will make a hormone called GnRA which
then controls the production and release of anterior pituitary hormones, FSH, follicle stimulating

hormone, and LH, luteinizing hormone, and these hormones then control target structures, in this
case they are usually gonadum, parts of the reproductive system. So the hypothalamus will make
a releasing or inhibiting factor that controls the activity of secretory cells in the anterior pituitary.
There are six hormones made by the anterior pituitary. Four of them are classified as
tropictropic means one hormone controlling another hormonethose are FSH, LH, ACTH,
and TSH. The other two hormones are nontropic, and those are GH and PRL, GH is growth
hormone and PRL stands for prolactin. There are six total secretions made by the anterior
pituitary and these control most of the other physiological activities going on in the body.
Let us talk about the individual anterior pituitary hormones and what they do. Later on in
the term we will talk about reproduction and the production of gametes, and that is all controlled
hormonally. The two hormones that are made by the anterior pituitary that control reproduction
are FSH and LH; these are not exclusively female hormones, these are also present in males, but
these were first characterized in females, so they got their names based on what they were doing
in the female reproductive tract. FSH stands for follicle stimulant hormone; in the female gonad
there is something called the follicle, the egg develops inside of the follicle and so FSH controls
the development of the gamete, the egg itself, so it controls gamete formation in both males and
females. In females, FSH also controls the production of estrogen. LH, for both males and
females, controls the production of gonadal hormones: for females that is estrogen and
progesterone and for males that is testosterone. So FSH and LH are the gonadal hormones, and
that is why they are called the gonadal tropids. These hormones are controlled by the
hypothalamus, and the hypothalamus, as I said a second ago, produces a releasing factor called
GnRH, which then controls the production and release of FSH and LH made by the anterior
pituitary.

The next anterior pituitary hormone is ACTH, standing for adrenocorticotropic hormone,
and that controls another endocrine gland called the adrenal cortex. The hypothalamus produces
a releasing hormone called CRH which controls the anterior pituitary, which produces ACTH
which then controls the production of cortisol, which is produced by the adrenal cortex.
The next anterior pituitary hormone is TSH, thyroid stimulating hormone, and that
controls the activity of the thyroid hormone. The hypothalamus produces TRH, thyroid releasing
hormone, which controls the release of TSH from the anterior pituitary.
Those are the tropic hormones. The nontropic hormones do not control the production of
any other hormone, they have direct on the cells of the body via the receptors. Where these other
hormones have their effects depends on where the receptors are. Prolactin, abbreviated PRL,
controls the production of milk by the mammary gland, so the only time it is going to be
produced is when a woman is lactating. It is controlled by a hypothalamic hormone called PIH,
standing for prolactin inhibiting hormone, which essentially inhibits the release of prolactin from
the anterior pituitary. So prolactin will not be made unless we stop making PIH, so during the
terminal stages of pregnancy and the transition to post pregnancy, PIH will stop being made,
prolactin will be made, and milk will be produced by the mammary glands. That does not
happen until a few days after the child is actually delivered; even though it appears that lactation
is going on, the first couple days it is not milk, it is something else called collosterone.
The last anterior pituitary hormone is growth hormone, though its name is inaccurate.
Growth hormone itself does not cause growth, it creates conditions that are favorable for growth,
but it does not actually make your bones any bigger nor your muscles. The direct effects are
called gluconeogenesis, the gluco stands for glucose, the neo stands for new, and genesis means
to make. So in order for us to grow, we are going to need additional cellular energy, and growth

hormones primary response is to cause glucose to be formed and broken down, cellular
metabolism providing enough energy to allow growth. The actual skeletal growth, the effects of
growth hormone that we think of, is indirect. The growth hormone will activate another factor
called the IGF, insulin-like growth factors, and they are insulin-like not because they do what
insulin does, but because they have an aminoacid sequence and structure very similar to insulin.
The insulin-like growth factors, once activated by growth hormone, cause muscular and skeletal
growth. Without growth hormone, the IGF would not cause muscular and skeletal growth, but
the growth hormone, without IGF could not do it either, so both are required. There are two
factors from the hypothalamus that control the release of GH, called GHIH and GHRH. GHIH
has another named called somatostatin, and this inhibits the release of GH, and GHRH, also
known as somatocrinin, causes the release of GH.
Let us talk about the actual individual glands of the endocrine systems, what they make,
and what they do. Let us start with the pancreas. The pancreas is actually two glands, it is both
exocrine and endocrine. If you remember, exocrine glands have secretory units and ducts, and
the ducts deliver the products to some limited space. The exocrine part of the pancreas makes
digestive enzymes. The pancreas is also an endocrine gland, having a population of cells called
the islets of langerhans, and these produce two kinds of cells: alpha cells and beta cells. Alpha
cells make glucagon, beta cells make insulin. When blood glucose levels drop, glucagon is
released. In our bodies, we store glucose in a complex macromolecule called glycogen, so
glucagon causes glycogen to be broken down into glucose, and then glucose can be used and
broken down to do cellular work. When blood glucose levels are elevated, insulin will be
released which causes glucose to be taken up by the cells and therefore cause glucose blood
levels to go back down. So there are two hormones made by the pancreas, glucagon by the alpha

cells, insulin by the beta cells, glucagon is released in response to dropping blood glucose levels,
insulin is released when blood glucose levels increase.
Let us now talk about the next endocrine gland, the thyroid gland. Most of us know that
our thyroid gland is on the anterior surface of our trachea and parallels on both sides. If you
zoom in and look at the thyroid, you will see that it is made of little spherical functional units
called follicles. If you look at an individual follicle, it is made up of individual cells called
follicular cells. The middle of the follicle is full of a substance called colloid. The follicles job
is to make a protein called thyroglobulin. The thyroglobulin is then put into the colloid inside
which iodine is added to the thyroglobulin. They then move back into the follicular cells which
then cut out the regions of the thyroglobulin that have been iodinated. Let us say there is this big
protein molecule here called thyroglobulin, and we add iodine to it, and then the regions which
have iodine are cut out and then assembled together. The actual production of the protein is
inside the follicular cells, it is iodinated in the colloid, once it is iodinated it is brought back to
the follicular cells, the little regions with iodine are cut out and then they are assembled together
to form T3, triodo, or T4, tetraiodo. The 3 represents 3 iodines, and the 4 represents 4. The
whole process of making thyroid hormone is taking place in these cells. Sometimes one part of
the process does not take place in the cells themselves, it takes place inside of this stuff called
colloid, then the final protein is just these small little snippets out of the big thyroglobulin that
are then pieced together to form the thyroid hormone.
The thyroid hormone controls cellular metabolism, how rapidly the cells are metabolizing
glucose to release energy and be able to do cellular work, so elevated levels of T3/T4 increase
cellular metabolism and the more cellular work you can do. This hormone is also controlled by
the hypothalamus: TRH released by the hypothalamus controls TSH from the anterior pituitary,

which then controls the production of T3 and T4 of the thyroid gland, and T3 and T4 control
cellular metabolism. One more thing about the thyroid gland: besides the follicular cells, there is
another group of cells in the thyroid; in addition the thyroid also produces calcitonin. There is a
group of cells called the C-cells which make calcitonin. When calcium levels go up, calcitonin is
released and causes calcium to be taken out of the blood and stored in the bones.
There is another gland built inside of the thyroid that is not related to the thyroid at all,
called the parathyroid gland. If you flipped the thyroid around and looked at the backside, you
would see integrated into the back of the thyroid gland another gland called the parathyroid
gland. The parathyroid gland has cells called sheath cells, and they produce PTH, parathyroid
hormone. When calcium levels drop, that leads to PTH release, and PTH regulates calcium in a
couple different ways. One thing that it does is that it activates the osteoclasts, the cells that
break down bone, which break down the bone and release calcium into the bloodstream. In
addition to that effect, PTH also stops you from excreting it in your urine, it makes the kidney
reabsorb the calcium out of the filtrate and put it back into the bloodstream. Also, PTH does not
directly activate vitamin D but creates a precursor to vitamin D, and vitamin D gets activated by
UV in your skin, and then vitamin D causes calcium to be reabsorbed out of the intestinal tract.
So PTH has three effects: it activates osteoclasts, causes the kidney to absorb calcium and put it
back into the body, and also is involved in the formation of vitamin D, and then vitamin D causes
the intestines to absorb calcium and put it into the blood.
Now let us go to the adrenal gland. The adrenal gland is a pretty complex gland. If we
took the adrenal gland and cut it in half, and looked at it inside, you would see that there is an
inner area called the medulla, and a superficial area called the cortex; a cortex is something that
has layers. The cortex is actually three different layers, but let us talk about the medulla first.

The medulla is really an extension of the sympathetic nervous system, but instead of releasing
their secretions onto some single target, they release their secretions into the bloodstream where
they act as hormones. For humans, the primary hormone released from our adrenal medulla is
epinephrine, also called adrenalin, which is released whenever the sympathetic nervous system is
activated and does everything the sympathetic nervous system does: elevates your heart rate,
blood pressure, and respiratory rate. When we think about the adrenal gland, we usually think
about a gland that is activated to deal with stress, it is there to provide additional physiological
resources to deal with stress. One comment about stress: this is biological stress, your brain does
not know the difference between the stress created by our complex society and a large predatory
animal chasing you, so your body responds to the stress that we have constructed in our complex
society as if it is a biological stressor. The only thing about biological stressors, you actually use
the physiological resource to deal with that stress. In sociological stress, none these changes
benefit you in any way. Does it make recovery of stored information any better, to have your
sympathetic nervous system activated? No, just the opposite; have you ever been in a stressful
situation and could not even remember your own birthday? It was made to aid in biological
short term stressors, where you either escape or are some other animals lunch. We also have
long term stressors. The other part of the adrenal gland, the adrenal cortex, deals with long term
stress. There are stressors in the biological world that do not go away immediately; there are
conditions where there are extreme environmental conditions that do not go away, reduced
availability of resources, water, food, extreme temperatures, those are all stressors. You cannot
have your sympathetic nervous system activated all the time, it is too taxing, we need a system
that will change the body to provide resources that persist longer, and that is what the adrenal
cortex does. The two resources provided by the adrenal cortex are to increase cardiac output and

to increase glucose levels. The glucose provides the cells with the substrate necessary to do
cellular work, and cardiac output provides the cells of the body oxygen and nutrients so that they
can do the physiological activity required of them necessary for survival.
The adrenal cortex has three layers and each one of those layers produces hormones. The
two primary adrenal cortical hormones are aldosterone and cortisol. If you remember from our
discussion on heart function, aldosterone increases sodium reabsorption, which increase solute
concentration, which activates osmoreceptors, which causes ADH to be released, which increases
water reabsorption, which increases blood volume, EDV, stroke volume, cardiac output and
blood pressure, which will deliver more oxygen and nutrients to the cells of the body so that they
can do more work to deal with the stressor. The trouble in the sociological context is that there is
no physiological work that needs to be done; just because your life is stinking complicated does
not mean you benefit at all from aldosterone, so now you just have elevated blood pressure for
no good reason. And that is why people in our complex society often have hypertension, because
we have chronic long term stress, but it does not require physiological resources. Your brain and
endocrine system do not know that it is not a real stress, but only a perceived stress. There is no
real stress at all, we allow it to be stressful, and we buy into this complicated system of
secondary enforcers, where we say all these things are valuable and important, but are they
really? Absolutely not. There is no primary biological benefit to the grade that you get in
general biology this summer. You cannot take it down to the grocery store and buy this weeks
groceries with it.
So aldosterone increases cardiac output. The other hormone is cortisol, which is
controlled by CRH from the hypothalamus. CRH causes the release of ACTH from the anterior
pituitary, which causes the release of cortisol. Cortisols primary effect is to cause

gluconeogenesis, the production of new glucose from other metabolites, aminoacides and lipids.
We convert other complex macromolecules and intermediates into glucose, and now that glucose
is available to do physiological work. The problem in the sociological context is that there is no
physiological work to be done, so what do we do with the extra glucose? We make it into fats
and we store it. And what happens to people who have chronic levels of elevated glucose over
the course of many years? They get type II diabetes, not the loss of beta cells from the islets of
langerhans resulting in the failure to produce insulin, but instead elevated levels of glucose
because of the bodys response to perceived stress. It is not real at all.
The next glands are the gonads, which we will talk about in more detail when we do
reproduction. They produce hormones that control, at various stages of life, the acquisition of
secondary physical characteristics; in lower animals, behaviors necessary to reproduce; and also
the ability to produce gametes in humans. These hormones are involved in regulating the
production of gametes and to some extent, making behaviors associated with reproduction
permissive, meaning to allow or promote them, but not elicit them. In animals, the presence of
these hormones is what induces all of those behaviors you see on those nature shows, like the
male moose banging their antlers together, all elicited by hormones directly. Human behavior is
affected by our hormones, but we are not going to be banging our antlers together. Although
hormones do affect reproduction, there was a time when humans were like a herd animal. In the
animal world, there is a certain time of year where there is a much greater probability of the
young surviving. You cannot have baby deer in December. When the females are able to
produce gametes and become receptive is all controlled by hormones to cause the greatest
probability of reproductive success. Humans used to have a similar kind of cycle, now we do
not, but we still have the capacity; if women cohabitate together in the same physical

environment like dorms, the women will all cycle together, and that is a kind of volatile hormone
called pheromone.
There are other hormones in other glands, for example there is the pineal gland which
produces melatonin. Melatonin regulates circadian rhythm, it does not actually make you sleep,
but it coordinates your brain activity levels with day and night cycles.
Another gland is the thymus gland; remember when we talked about immune function,
the thymus was the site of the maturation of T cells. The thymus actually produces hormones to
regulate T cell maturation, one that inhibits and one that causes it.