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Lecture Notes: Introduction to Endocrinology: "Gland to meet you."

Objective 75-1: Identify the general characteristics of hormones and the glands
they come from.

Hormone definition
o A chemical substance
o Secreted by a gland or a group of glands, or a tissue, into body fluid
o Has a physiological control effect on other cells of the body

Endocrine definition
o Endo = within
o Crine = secrete
o Endocrine = secrete within the body
o Contrast with exocrine (secrete outside of the body)

Hormonal effects can occur during various time scales.

o seconds (norepinephrine, epinephrine),
o several days, weeks,
o months (thyroxine, growth hormone).

The nervous system can interact with hormonal system.

o Sympathetic nervous system can stimulate adrenal glands
o Central nervous system can control the pituitary gland
o Some (but not all) hormones are controlled by nervous system.

The endocrine (hormonal) system controls different metabolic function of body.

o Chemical reaction rate of cells
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o Transport of substances through cell membrane

o Growth of body
o Secretion of other hormones

Introduction to the types of endocrine glands and tissues

There are approximately nine types of endocrine glands and tissues. In fact, there can be more
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or less depending on the criteria and the source of information you look at. It is complicated
since some of these glands have multiple copies, and some have different internal parts that
count as a gland.

1. pituitary
2. adrenal (each kidney has one) insulin
3. thyroid
4. parathyroid
5. islets of Langerhans
6. ovaries
7. testes
8. placenta
9. duodenum

1a. There is one pituitary gland which has two halves. One half is the anterior pituitary, which is
pointed to the front of the body. It is primarily controlled by other hormones that we review
later. It actually secretes six hormones:

o growth hormone,
o adrenocorticotropin, (stimulating hormons)
o thyroid-stimulating hormone,
o follicle-stimulating hormone,
o luteinizing hormone,
o prolactin
o last 3 sexual hormones

1b. The other half is called the posterior pituitary. It is pointed to the back of the body. It is
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primarily under neuronal control (meant to be fast). It secretes two hormones:

o antidiuretic hormone, (flow of water in kidney and BP)

o Oxytocin (breastfeeding)

2a. There are two adrenal glands, one on each kidney. Each adrenal gland has two parts. The
adrenal cortex is the outer part of the adrenal gland. It is under hormonal control. It secretes two
hormones (It secretes more than just two, we will expand on that during the adrenal gland
lecture)
o cortisol
o aldosterone
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2b. The adrenal medulla (under control of sympathetic NS) so in danager brainstem will send n
to medulla will secrete adrenaline) is the inside part of the adrenal gland, it is under neural
control. It secretes two "catecholamine" hormones:
o adrenaline (epinephrine) , this the major secretion (stress,
o noradrenaline (norepinephrine) , this is the minor secretion
o ( how to reduce adrenaline stress? public speaking, math tests, and no and subtract
numbers.)

3. The thyroid gland is located up in the sternal and mediastinal area of the thorax. It is situated
above the thymus, which sits on top of the heart. The thyroid has various shapes but generally
has two lobes. It is kind of shaped like a moth or butterfly. It secretes three hormones.
Regulates temp, energy expenditure.
o thyroxine (T4)
o triiodothyronine (T3)
o calcitonin (bone tissue and calcium)
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Parathyroid (all four

pink dots)

Thyroid
(the whole yellow
part)

4. There are four parathyroid glands, they are located within the thyroid gland. Even though it is
within the thyroid gland, the parathyroid gland is considered a separate gland due to its
completely different control and function. It secretes one hormone:
o parathyroid hormone (parathormone)

5. There are millions of islets of Langerhans are in the pancreas. They are not really considered
a gland, rather, they are an endocrine tissue. They secrete several hormones including:
o insulin
o glucagon Pancreas

6. There are two ovaries; they are considered an endocrine gland. They produce hormones
including:
o estrogens
o progesterone

7. There are two testes (testicles), portions of them are considered an endocrine gland. They
produce hormones including:
o Testosterone
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8. The placenta (during menstruation, conception and gestation) is considered an endocrine

tissue, it makes hormones including
o human chorionic gonadotropin
o estrogens
o progesterone
o somatomammotropin

9. The duodenum (small intestine) contains Brunner's glands, considered an endocrine gland.
o secretin hormone signals to the pancreas, (Ch 64 ed 12)
o coordinates digestion

Objective 75-2: Identify the basic chemical types of hormones and their
mechanisms of target actions.

Hormones can be classified as local hormone or general hormone according to the range of their
effect. This definition is not perfect but can help us understand the action of the hormones.

1. Local hormones primarily have specific local effects on specific tissues (target tissue). It is
not based on where they come from, but where they have their effect.

o Example: secretin.
 can be considered a local hormone.
 Released from duodenal (intestinal) wall, transported in blood to pancreas, cause
pancreas secretions for digestion.

o Example: Cholecystokinin
 can be considered a local hormone.
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 Released in small intestine, transported to (1) gallbladder cause gallbladder

contraction,(2) pancreas cause secretion of digestive enzyme.

o Example: Adrenocorticotropin
 can be considered a local hormone.
 Released from anterior pituitary gland, stimulates adrenal cortex to secrete
adrenocortical hormones

2. General hormones can be effective on many parts of the body and cause many different
reactions.

o Epinephrine (E) and Norepinephrine (NE)

o secreted by adrenal medullae under sympathetic stimulation.(on almost every cell in
our body)
o secreted by sympathetic nerves.
o cause constriction of blood vessels and increase of arterial pressure
o has effects on most organs and tissues of the body

o Growth hormone (GH)

 Released from anterior pituitary gland
 Cause growth in all parts of body

o Thyroid hormone (T3 and T4)

 Released from thyroid gland
 Increase chemical reaction rate in almost all body cells
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Hormones can also be classified based on their basic chemical structure. Understanding this
also helps us understand how the hormone is produced, and how it works on the body.
Hormones can be classified chemically into three types, steroid, protein, and tyrosine.

1. Steroid-based hormones are built from cholesterol. Here is a picture of the cholesterol
molecule (left), and a major source of cholesterol (right). Do you know what kind of food is on
the right?

Now we will look at the various hormones based on cholesterol, they are called steroid
hormones because testosterone is built from cholesterol, and many anabolic steroids are made
from testosterone.

Steroid hormones are based on the cholesterol molecule. The adrenal cortex will turn the
cholesterol into many other hormones including cortisol and aldosterone. The placenta and
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ovaries can also turn cholesterol into estrogen. And the testes can make testosterone out of
cholesterol.

So cholesterol is not so bad after all, your body needs some to make hormones. But that doesn’t
mean you should all go out and eat a giant plate of poutine always!

The steroid hormones tend to cross the plasma membranes of cells and get direct access to the
inside of the cell (cytoplasm and nucleus). This happens because cholesterol is hydrophobic, it
"hates water" , therefor, it is lipophilic "loves fat". This biochemical characteristic means that
the receptors for steroid hormones are usually found within the cell cytoplasm or nucleus.

Mechanism of steroid hormone action follows a general pathway:

Steroid hormones enter cytoplasm of cell  bind with receptors*  diffuse or
transported into nucleus  bind to and activate DNA strands  initiate
transcription process of genes to form RNA messenger  RNA goes into cytoplasm
through nuclear pore complex  promote functions inside the cells.
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*In some cases the receptors are found within the nucleus not the cytoplasm.

2. Now, we will examine the tyrosine-based hormones more closely. You know tyrosine is an
important amino acid to make proteins, but it can also be turned into several different
hormones. The thyroid gland can turn tyrosine into thyroxine (T4) and triiodothyronine (T3).
The adrenal medullae can turn tyrosine into epinephrine and norepinephrine.

Even though the two glands use tyrosine to make hormones, the biochemistry is quite different.
The thyroid gland adds iodine molecules to tyrosine which makes T3 and T4 hydrophobic
(lipophilic). The adrenal gland hydroxylates tyrosine which makes it hydrophilic (lipophobic).

For these reasons, T3 and T4 have their receptors inside of the cells for the same reasoning that
we went though for the steroid-based hormones.
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For thyroid hormones there is a chain of events leading to their action on the body:

Thyroid hormones  bind with receptor in cell nucleus*  bind and activate DNA
 initiate transcriptions of specific genes to form RNA messenger  RNA goes
into cytoplasm through nuclear pore complex  new proteins (enzymes) are formed
and become the controller to promote metabolic activities in all cells of body
*In some cases the receptors are found within the nucleus not the cytoplasm.

For epinephrine (E), norepinephrine (NE), also including acetylcholine (Ach), they must
interact with receptors on the cell surface. There is a chain of events leading to the eventual
function on the body.

E or NE  bind with receptors on the cell membrane  cause conformational

change of proteins structure of the receptor  open or close channels for ions (Na or
K) (change of membrane permeability)  change of cell membrane potential 
cause cell excitation or inhibition
3. The third and final category of chemical hormone is protein or peptide-based hormones. A
protein is a long chain of amino acids that fold up into an organized blob. A peptide is a much
shorter version, it is technically less than 20 amino acids long, so it doesn't seem to fold into a
blob. Both types have similar biochemical properties so we consider them the same for this
course. Here are some examples:

Hormone Released from

anterior pituitary hormones anterior pituitary
posterior pituitary hormones posterior pituitary
insulin and glucagon islet of Langerhans
parathormone parathyroid gland
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All of the protein and peptide-based hormones are hydrophilic, (lipophobic) so they prefer to used
receptors on the surface of cell membrane. A chain of events leads to their eventual function on the
body.

Protein or peptide-based hormones bind receptors on membrane (protrudes to exterior of cell)

 structure change in receptor  receptor becomes activated enzyme "adenyl cyclase"
 activate the formation of "cyclic adenosine monophosphate" (cAMP)  second
messenger activates a cascade of enzymes  cause powerful effects on cells

Objective 75-3: Identify the more common types of intracellular "second

messenger" mediators of hormonal effects and functional significance.

Second
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messengers are cell-signalling pathways that communicate between the receptor on the cell
surface and the inside of the cell. Each receptor has a unique pathway, and some receptors can
use different pathways. We review some common examples.

o Cyclic adenosine monophosphate (cAMP) as second messenger

Hormones  receptor  activate enzyme "adenyl cyclase"  activates the

formation of cAMP  activate a cascade of enzymes  cause different effects on
cells.

o Ca2+-Calmodulin as second messenger

Hormones  receptor  open channels for Ca2+ ions  Ca2+ diffused into cell
and bind with calmodulin  calmodulin is activated by conformational change 
activated calmodulin can cause multiple effects inside the cell in the same way that
cAMP does

Example: smooth muscle contraction

Ca2+  diffuse into smooth muscle membrane  bind with calmodulin 
Ca2+-calmodulin complex activates myosin kinase (enzyme)  cause the
phosphorylation of myosin head of smooth muscle  formation of cross-
bridge for muscle contraction

o IP3 and diacylglycerol as second messenger

Hormones  receptor  activates enzyme phospholipase C attached to the inside

projection of the receptor  cause phospholipids in the cell membrane to split into
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small substances such as inositol trisphosphate (IP 3) and diacylglycerol that serve as
"second messenger"
Objective 75-4: Recognize the magnitude of hormonal concentrations in the
blood, their means of measurement, and their significance.

Measurement of Hormone Concentration in Blood

Concentration of hormones is extremely low in the blood. The levels range from few
picograms/mL, and as high as a few micrograms/mL. The rate of secretion of hormones is
extremely small, it is measured in microgram/mL/day. Hormones are very small chemicals
molecules that defy conventional measuring techniques. There are some fancy ways of
measuring them.

Hormones can be measured by the method of radioimmunoassay (RIA)

The company sells a kit to measure it. They have made an antibody in large quantities (in mice
usually) that is highly specific for the hormone to be measured.

o A small quantity of that antibody is mixed simultaneously with (1) an amount of fluid
containing the hormone to be measured, (2) an amount of the purified standard hormone
tagged with a radioactive isotope. The "standard" is also something the kit contains, its
concentration is known, so you can use it to figure how much hormone is in the sample.

o The natural hormone and the radioactive standard hormone compete for the binding sites of
the antibody. In the competing process, the number of each of the two hormones (natural and
radioactive) that bind with the antibody is proportional to its concentration
o After the binding has reached equilibrium, the antibody bound with hormones is separated
from the remainder of the solution, and the amount of radioactive hormone bound with
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antibody is measured by radioactive counting techniques



o The concentration of the natural hormone can be determined by comparing the

radioactive counts recorded with a standard curve that correlates the percentage of
antibody bound with radioactive hormones to the concentration of the natural hormone to
be measured
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o The higher the percentage of bound radioactive hormone, the lower the concentration of
the natural hormone to be measured

Another way to measure the hormones is mass spectrometry.

o a radio-labelled standard of the hormone is bought from a company.

o The mass spectrometer determines the profile of the standard.
o The sample is run in the mass spectrometer and compared against the standard.
o This method can be very precise and very quantitative. However, it is technically very
demanding, expert scientists and expensive infrastructure are required.

Objective 75-5: Define some general concepts of how hormone levels are
controlled in the body.

An important aspect of hormones, is the control of their secretion rate. By controlling the
secretion rate, the body can control how much effect the hormone is having, and it can 'shut off'
the hormone secretion if there is too much. Its not really an 'on / off' switch, rather, its
homeostasis. Most hormones are at a steady state and can be adjusted down and up as needed.
Negative feedback is the most common way hormones are controlled. There are two kinds,
direct and indirect.

Direct negative feedback is when the hormone inhibits its own secretion when it reaches a high
enough level.

Gland secretes hormone  hormone accumulates in blood  hormone gets back to

gland  hormone inhibits its own secretion.
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Indirect negative feedback is when the "effect" of the hormone inhibits the hormone secretion.
Gland secretes hormone  hormone accumulates in blood  hormone stimulates a
tissue  the tissue produces some effects, for example, heat is produced  the
effects, in this example heat, will go back to the gland and inhibit the secretion of the
hormone.

Positive feedback is a third type of feedback that is less common because it is hard for the body
to control it. Here is a chain of events that explains direct positive feedback:
Gland secretes hormone  hormone accumulates in blood  the hormone goes back
to the gland and promotes the secretion of the hormone.

Positive feedback can also be indirect:

Gland secretes hormone  hormone accumulates in blood  the hormone stimulates a tissue
 the gland and produces some effect which then promotes the secretion of the hormone.

Hormonal control is also regulated by circadian rhythm, this is the day/night cycle. When we go
to sleep different hormones go up or down. When we wake up, different hormones go up or
down. There are also season rhythms to certain hormones.

The last thing to consider is how a hormone's receptor is regulated. Even if a hormone is
secreted, it still needs a receptor somewhere to be effective.

o The number of receptors in the target cell varies from day to day even from minutes to
minutes..
o Receptors can be activated or deactivated by altering their second messenger cell
signalling pathway, or by altering their location in the cell.
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o Receptors can be destroyed by enzymes, then they are just gone.

o Receptors can be created by synthesis, so now there are more of them.

Chronic over-stimulation of a receptor will lead to a deactivated or destroyed receptor. Now the
hormone can not have an effect for awhile until the receptor is reproduced.

Drugs also have a huge impact on hormones and their receptors. We wont go much into this
aspect in EXCI360, but it is covered extensively in EXCI461 Pharmacology for Sport and
Exercise.

End of introduction.