>>Dr. Ketchum: In this segment, you will learn how cortisol—a steroid hormone—is synthesized
and secreted, and how that synthesis and secretion of cortisol can be turned off. You will also
learn the various functions for cortisol. To begin, it’s very important that you understand
what causes the synthesis and secretion for cortisol. Synthesis and secretion
may be stimulated by prolonged fasting, by prolonged exercise, by stress—hence the
reason cortisol is often called the stress hormone, and lastly, circadian rhythm. So
we tend to synthesize and secrete cortisol during the day and we do not secrete cortisol
at night. So the levels of cortisol will vary depending upon the circadian rhythm. So to
begin the cortisol feedback loop, we will begin with the hypothalamus. So the hypothalamus
is a region of the brain, it’s near the center. Inside of the hypothalamus we have
some cells that are called neurosecretory cells. These neurosecretory cells or neurosecretory
neurons, to be more specific, will synthesize and secrete various hormones. In this case,
the neurosecretory neurons will synthesize and secrete a hormone called corticotropin-releasing
hormone, known as CRH. The hypothalamus is the only organ that will synthesize and secrete
releasing hormones. So any time you hear about a releasing hormone, you can automatically
assume it was synthesized and secreted by the hypothalamus.
Okay, so when the neurosecretory neurons synthesize and secrete corticotropin-releasing hormone,
it travels down the axon of that neuron and into the axon terminal. So once CRH reaches
the axon terminal, it is secreted. When CRH is secreted, it will move into what’s called
the hypophyseal portal system. This is a link or a bridge between the hypothalamus and the
anterior pituitary. Once CRH arrives at the anterior pituitary, corticotropin-releasing
hormone will bind to receptors on the endocrine cells. This will stimulate the anterior pituitary
to synthesize and secrete another hormone called ACTH. ACTH stands for adrenocorticotropic
hormone. ACTH then will enter into the systemic circulation, so now it can travel through the body.
ACTH will specifically target the adrenal glands. The adrenal glands sit on
top of the kidneys. So here you can see the kidneys, and the kidneys have a hat. The hat
is called the adrenal gland. To be more specific in terms of the adrenal gland, the adrenal
glands have two regions. The center of the adrenal gland is called the medulla; that’s
the most interior region of the adrenal gland. The outermost part is called the adrenal cortex.
This adrenal cortex consists of three layers. The outermost layer is the zona glomerulosa.
The middle layer is called the zona fasiculata, and the innermost layer of the cortex is called
the zona reticularis. Now adrenocorticotropic hormone (ACTH), when it targets the adrenal
glands, it specifically will target the zona fasiculata. So ACTH binds to receptors on
the zona fasiculata and that stimulates the zona fasiculata to synthesize and secrete
cortisol, your stress hormone. Now the zona fasiculata mainly—it’s main role is to
synthesize and secrete cortisol. Cortisol then can enter into circulation and once it’s
in circulation, then it can have an effect on several different target tissues. Cortisol
can target adipose tissue. Now when we talk about adipose tissue with respect to cortisol,
we’ll be speaking about visceral adipose tissue and peripheral, or what’s called
subcutaneous adipose tissue. So in either situation here, when cortisol targets the
visceral or the peripheral adipose tissue, lipolysis occurs. And so when lipolysis occurs,
we know that we can take a triglyceride and we can break it down into our fatty acids
and into glycerol. Glycerol then can be converted to glucose in the liver, and when we do that,
that will increase glucose levels in the plasma. Fatty acids can enter into circulation, so
you can increase the amount of fatty acids in the plasma. But also, fatty acids can go
into the liver, and they can be converted to acetyl CoA. They can then be converted
to ketone bodies via a process called ketogenesis, and when those ketone bodies get produced
via ketogenesis, they enter into the bloodstream. So the level of ketone bodies can increase
in the plasma. Cortisol will also target skeletal muscle, and when it targets skeletal muscle,
that will cause proteolysis. And proteolysis, you know, the product are amino acids. So
those amino acids can go into circulation so we can increase the concentration of amino
acids in the plasma, but those amino acids can also go into the liver. And when they
go into the liver they can be converted to pyruvic acid and then into glucose, which
will also increase your glucose plasma concentration.
So now in the bloodstream as a result of cortisol release, we have an increased plasma glucose
concentration, increased amino acid concentration, increased ketone bodies, and increased fatty
acids. We can take all of these into our visceral adipose, and we can store all of these as
fat, as triglycerides. So if we store them as fat, we’re preparing the body for another
stressful event. This demonstrates the normal function for cortisol. Let’s go ahead and
move onto the next page, where we talk about situations where you have a prolonged stressful
situation, so you have prolonged cortisol release. Chronic stress is bad. Some stress
is okay; too much stress is a bad thing, and we call that negative stress. So let’s take
a look at what happens under those conditions. To begin we have the visceral fat here, which
is the fat that lines around the internal organs and then here’s the subcutaneous
fat, and that’s your peripheral fat or part of it, anyway. We’re only focusing on the
stomach here. And so under conditions where you have chronic stress and you continue to
release glucose into the bloodstream, fatty acids into the bloodstream, amino acids into
the bloodstream, you will store those as fat, and you store them as visceral fat. So people
that are under chronic stress, negative stress, tend to have belly fat.
Cortisol, or negative stress or chronic cortisol release, can also have negative effects on
the brain. Let’s look at the three negative effects that can occur on the brain. There
are various regions in the brain, and one of those regions is called the hippocampus.
Chronic stress or chronic cortisol release will atrophy the hippocampus—in other words,
it starts to break down or destroy itself. The hippocampus’ normal function is to convert
short-term memory into long-term memory. So if your hippocampus atrophies, meaning your
cells are dying in the hippocampus, you have an inability to convert short-term memory
into long-term memory. In essence, you have memory loss. Now chronic cortisol release
can also damage the prefrontal cortex. The prefrontal cortex is very important. It enables
us to concentrate, for example, enables us to make decisions. And so if we damage the
prefrontal cortex due to chronic cortisol release, this can lead to an inability to
concentrate and it can also lead to depression. Chronic cortisol release can also cause another
region of the brain called the amygdala, and the amygdala is actually important in recognizing
fear. And so recent studies have suggested that chronic cortisol release can cause the
amygdala to generate anxiety and depression. So people that tend to be under a lot of stress
have anxiety problems as well as depression, and that may be because the amygdala is generating
that.
Now cortisol, chronic cortisol release can also atrophy the thymus. The thymus is very
important, because the thymus helps with your immune responses. So if cells of the thymus
are being destroyed like the cells of the hippocampus were, the thymus then can no longer
function in terms of the immune system. So you atrophy the thymus, you suppress the immune
response. Once we have cortisol synthesized and secreted, we need to turn it off. So once
we have cortisol in the systemic circulation, cortisol can have an inhibitory effect on
the endocrine cells of the anterior pituitary. They can inhibit the responsiveness of those
endocrine cells to CRH. If we inhibit the responsiveness of the endocrine cells to CRH,
the endocrine cells are less likely to synthesize and secrete ACTH: adrenocorticotropic hormone.
Cortisol, when it’s in circulation, will also come up and have an inhibitory effect
on the hypothalamus. And so when it acts on the hypothalamus, it inhibits the synthesis
and secretion of CRH. So if the hypothalamus does not synthesize and secrete corticotropin-releasing
hormone, there’s no signal to the endocrine cells of the anterior pituitary to synthesize
and secrete ACTH. Therefore, if there’s no ACTH binding to receptors on the zona
fasiculata, the zona fasiculata will not synthesize and secrete cortisol, and hence we have turned
off cortisol secretion.