Um, so, um, adrenal glands.

We've looked at hypothalamus, pituitary gland, and then we understand

that, uh, hormones are secreted from the hypothalamus, and the

pituitary gland.

Gland can actually, um, sort of continue to, um, regulate

secretion of hormones from other, um, endocrine glands.

We've looked through thyroid glands and how the HPT access

regulates, um, our sort of, um, thyroid functions and also

in general, um, sort of, um, effect produced by the

thyroid hormones.

In this lecture we're going to look at how hypothalamus

and pituitary gland, sacred hormones that regulate, um, the function

of adrenal glands.

So adrenal glands are located on top of each our

kidneys.

So we have two kidneys and then we have two,

um, adrenal glands.

Um, hopefully you've worked out how the hypothalamic hormones regulate

the anterior pituitary hormones.

Um, after the first lecture.

So in here we know that the, um, CRH, um,

released by the hypothalamus can activate Acth, um, release from

anterior pituitary, which will then act on the adrenal.

Adrenal cortex to regulate the secretion of adrenal hormones.

So in this lecture we're going to talk about the

structure of adrenal glands.

And we're going to talk about how the steroid hormones

are synthesised in the adrenal glands.

And we'll also take a look at the physiological actions

of um, steroid hormones that have been produced in the

adrenal glands.

And the lastly, we'll be looking at the regulation of

the adrenal function and then how disturbance of the, um,

sort of normal adrenal function will be related to various

adrenal Disorders.

Hopefully by the end of this lecture, you'll also know

why we have this statue.

Um, that's, uh, located in the Hodgkin building.

Do you guys go to Hodgkin Building often?

Right.

So if you walk into the sort of front door

to the left, um, you will actually see this person.

Um, by the end of this lecture, you will know

who he is.

I know why his statue is at guy's.

Uh, so the structure of adrenal glands, adrenal glands are

also called a super nano glands because they are located

on top of each our kidneys.

And obviously we have two adrenal glands, uh, one on

each, uh, kidney.

If we section the adrenal glands, we will see that

adrenal glands, um, are made of adrenal cortex and adrenal

medulla.

Adrenal cortex, um, is the, um, part of the adrenal

glands that are responsible for secreting, um, steroid hormones, for

example, uh, glucocorticoids, mineralocorticoid, which we will talk later, are

all being synthesised and produced and released in the adrenal

cortex.

Um, adrenal glands also has um, adrenal medulla, which is

the source of adrenaline and noradrenaline.

So adrenal medulla is really a extension of our sympathetic

nervous system.

Um, so it is actually distinct from the adrenal cortex.

If we look at um, adrenal cortex, which With its

sort of specific cell types and what hormones they're producing,

we will know that the adrenal cortex can also be

separated into three distinct, um, parts of zones.

So we have zona Rosa, which is the outermost layer

of cells in the adrenal cortex.

And those cells are responsible for making either store.

We also have zona facilita.

These are the, um, sort of cells that are responsible

for producing glucocorticoids, which are essential in regulating our metabolism.

Um, sort of underneath the zona physical Lata, we have

zona ridiculous, which is responsible for producing androgens.

So androgens, in addition to being produced by the reproductive

organs, um, some of them are also being produced by

the adrenal glands.

And lastly, in the adrenal medulla you will see adrenaline

and noradrenaline being produced.

We know that adrenaline and noradrenaline are responsible for regulating

our sort of short term stress response, like our fight

or flight response.

But then glucocorticoids that are secreted by the adrenal cortex

also regulates our stress response.

But these are mainly sort of responsible for regulating our

chronic stress response.

We will be focusing on those hormones in this lecture.

So all of the adrenal sort of hormones being produced

in the adrenal cortex are steroid hormones.

So they are lipid derived hormones.

Um, as I said earlier, those hormones are derived off

from cholesterol.

Um, cholesterol under conditions of different sort of um, the

presence of different enzymes will be converted into either stone

or it can be converted into cortisol and oestradiol and

testosterone based on which group of enzymes that are being

produced or present, in particular, um, types of cells.

Um, there are three sort of distinct group of, um,

steroid hormones.

Uh, in terms of the sort of adult storm, um,

it is a, um, one type of mineral, um, cortical.

It's uh, its main role is to actually regulate the

electrolyte homeostasis in our body.

Um, it does this by increasing the, uh, sodium reabsorption,

um, of the kidney.

And as a result of this, it can actually regulate

our blood pressure and the blood volume.

Um, it's a secretion is actually regulated by the reddening

angiotensin system.

We will have a look of how mineralocorticoid are regulated.

Um, a little bit later.

Um, a second group of corticosteroids are glucocorticoids.

Uh, cortisol is the, um, the type of glucocorticoid that

we're mainly interested in.

Uh, glucocorticoids, um, are sort of a group of hormones

that really regulate our stress response.

So when we have chronic stress, um, we will have

a lot of cortisol being produced by the adrenal glands.

These cortisol will have a profound effect on our metabolism.

Mainly, they can actually increase a protein catabolism in the

muscle.

So breakdown of proteins so that those sort of amino

acids can be actually used as a source of energy

to support our bodily function where we're under stress.

Um, glucocorticoids also increase gluconeogenesis in the liver.

So gluconeogenesis is the generation of glucose from non carbohydrates

substances for example amino acids, lipids um they can be

converted into glucose in the liver under conditions of chronic

stress.

And then it's easy to understand when we're under constant

stress.

Our body needs to actually try to divert the energy

to help us to actually have enough sort of fuel

to actually support the, the, the function of organs.

Um, as a result of gluconeogenesis in the liver, you

will have increased plasma glucose.

And this again is understandable because you have glucose being

generated from carbohydrates and the non carbohydrate substitute substances.

And this increased the plasma glucose is to actually support

the need for the fuel during during stress.

But um it also has effect on um our sort

of metabolism in the sense that when you have a

chronically elevated plasma glucose, you will be having a condition

of type two diabetes, meaning that those glucose that are

circulating in the blood will have a negative impact on

the cells in your body.

So that's why when we're under chronic stress and then

having continued release of the stress hormone cortisol, we also

will have sort of presentation of symptoms related to type

two diabetes.

Cortisol also stimulates caloric intake.

Um, which again is our sort of a way of

a coping system for, for chronic stress.

So all of this, um, regulates the, the, um, sort

of metabolism so that we can generate response to the

two to, to chronic stress.

Um, there's lots of people outside.

Does anyone want to open the door?

If you don't mind?

I don't know what they are.

Right.

Thank you.

Right.

Um, so that's, uh, the role of glucocorticoids in regulating

metabolism.

Glucocorticoids are also responsible, um, sort of, for suppressing our

immune response and inflammatory response.

And then again, this is our way of sort of

coping chronic stress.

Because when we're stressed, our immune response is not essential.

So we can actually shut this off so that it

can actually we can divert our fuel and energy into,

um, supporting the core, um, sort of organs of the

body.

But as a result of this, when we are under

chronic stress and the increased cortisol will actually cause, um,

response in our sort of immune system.

The way glucocorticoids work is by binding to the glucocorticoid

receptors that are located in the cytoplasm.

So glucocorticoid is a steroid hormone.

So it's a lipid derived hormone that can actually diffuse

through the cell membrane.

Once in the cell membrane who will bind to the

glucocorticoid receptors.

Glucocorticoid receptors are normally associated with a short protein.

And once the glucocorticoid binds to the glucocorticoid receptors, the

receptor will actually be dissociated, sort of dissociated from the

heat shock protein.

And this hormone receptor sort of binding complex will actually

enter the nucleus where it can regulate Regulates the gene

transcription and protein translation.

So those genes that actually have a sort of a

sequence of glucocorticoid response elements will respond to the um

hormone receptor complex, and the expression of those genes will

be under the control of glucocorticoids.

Um, androgen, um, is the other group of hormones that

have been produced by the, uh, adrenal cortex.

Um, we know that the majority of our androgens in

males, at least, are produced by the testes.

Um, androgens in females are mostly produced by the, by

by the, um, adrenal cortex, but some, some of.

Some of the small amounts of androgen can also be

produced by the ovaries.

We don't know the precise role of androgens that have

been produced by the by the adrenal glands.

They may be involved in the development of secondary sexual

characteristics during puberty, or they may have a role in

preventing sort of degenerative changes during ageing.

And this is a still active area of research.

So now that we know the different groups of hormones

that have produced by the adrenal cortex, how does those

hormone release, uh, being regulated?

Um, so we know that, um, adult strong um, being

a mineralocorticoid is being produced in the outer zone of

the adrenal cortex, and its release is under the control

of the renin angiotensin system.

Um, so it's sort of when you, um, when you

have a reduction in the plasma volume, the random will

be released by the, by the kidney, and then random

will convert angiotensin again into angiotensin one.

Angiotensin one will be further converted into angiotensin two in

various tissues.

Um, angiotensin two actually acts on the zona marula um,

in the adrenal cortex to stimulate the production of adult

serum.

And this adult strong um, in response to changes in

the plasma volume and the effect of renin will then

increase the sodium.

Sort of sodium reabsorption.

Um, so that when when we have more sodium being

reabsorbed, we can actually retain, um, sort of plasma volume

and the plasma, uh, sort of blood pressure.

And this is how the adult serum can help regulate

our blood pressure through regulating electrolytes homeostasis.

Glucocorticoids, uh, regulated through, um, uh, Acth.

So when Acth is released from the anterior pituitary in

response to stress, it can act on the receptors in

the cells in the zone of Lata.

And this binding of Acth to the receptors will stimulate

the cortisol production.

As I said earlier, cortisol, by binding to the cortisol

receptors and the regulator gene expression can actually cause protein

catabolism and i.e. break down the proteins to, to, to

to produce a source of energy and the fuel.

And then it also causes gluconeogenesis, among other effects, to

actually increase our sort of blood glucose levels.

And also cortisol is anti-inflammatory.

And, um, it will actually suppress our, um, our immune

system and immune responses.

Cortisol can actually have a negative, um, feedback effect on

the anterior pituitary and the hypothalamus to switch off the

secretion of Acth.

So if you think about how the, um, negative feedback,

um, sort of regulation work, you say that's when we're

under stress.

Um, our hypothalamus starts secreting, um, cr h um, and

then CRH will act on the anterior pituitary to trigger

the release of Acth.

And the Acth, then act on the adrenal cortex to

stimulate the secretion of cortisol and then cortisol, um, by

binding to cortisol receptors or glucocorticoid receptors, we will actually,

uh, suppress our immune system, um, to trigger the changes

in the metabolism.

Um, Um, and therefore, uh, sort of, um, generate various

conditions.

So if we have for whatever reason, um, that can

actually, uh, sort of.

Sort of increase this, um, sort of, um, the HPA

axis, we you will have a continued release of a

cortisol, uh, which could have a sort of a series

of metabolic effects on our body.

But normally, uh, we have a sort of negative feedback

regulation, uh, being in place where we can actually inhibit

the release of CRP and Acth in order to, um,

sort of switch off the production of the stress hormone

cortisol.

Um, but obviously there are times when when we, um,

when the stress or when the stimulus is too much

where we can't actually have sufficient compensation and when we

don't have sufficient compensation, and that's when we have, um,

sort of adrenal related disorders.

Um, as I said earlier, uh, with endocrine disorders, you

can either have deficiency of hormone or, um, overproduction of

a hormone or even the sort of a defect in

the hormone and the sort of hormone receptor, um, response.

Um, in terms of adrenal related disorders, if we have

a congenital adrenal hyperplasia, um, it will actually it basically

means we have deficiencies in the key enzymes that are

responsible for, um, synthesis of, of adrenal Hormones.

There will be some sort of some.

Sort of consequences.

Because most of the adrenal.

Hormones are steroid hormones and that are derived from the

cholesterol without those without those steroid hormones will have no

sexual differentiation.

Or we will have sort of lost ability to regulate

the electrolytes, um, sort of, um, homeostasis, which will result

in either hypertension or other related conditions.

But most of the, uh, sort of, uh, deficiency in

adrenal, uh, hormones are actually acquired later in life.

Uh, one of the most common adrenal disorder, um, that

are quite later in life is Addison's disease.

So Addison's disease is again a autoimmune disease.

Um, with autoimmune diseases, we don't really know, um, what

is the cause of it?

But it is generally believed that, um, some sort of,

um, infection, tuberculosis or, um, some sort of external figure,

a trigger can actually have an impact on our immune

system, which makes our immune system to falsely attack one

of the hormones that are normally being produced.

And then in the case of Addison's disease, it is

when our immune system attacks the the cells that produces,

uh, cortisol.

And as a result of this, um, we won't be

able to have cortisol.

Um, and as I said, the cortisol is a really

important thing in regulating our metabolism and immune responses.

And then this is why when someone having Addison's disease,

having have to be treated by hormone replacement therapies.

Thomas Edison, um, he wrote a article called The Constitutional

and the Local Effect of the disease of the soprano.

Um capsules.

Soprano capsules, meaning, um, adrenal glands.

So he was the first person who actually described a

clinical condition associated with with hormone.

And because of this, he was considered of the the

founder of the clinical endocrinology.

He studied and worked at Guy's Hospital.

Um, um, and then therefore, um, sort of, um, we

have a statue of Thomas Edison Atkins.

Um, this is another famous person being treated or suffered

from Addison's disease, but he was also one of the

first person to be treated by the hydrocortisone, which is

a form of synthetic form of cortisol.

And he responded very well to to the to the

treatment.

And his, his sort of condition was able to be,

um, sort of maintained properly as opposed to on the

production of um, cortisol.

We can also have overproduction of um, of glucocorticoids.

And this causes a condition called um Cushing's syndrome.

So this is when you either have a tumour in

the pituitary or the adrenal glands, which will, trigger the

release of.

Overproduction of glucocorticoids and um.

Occasionally Cushing's syndrome can also be associated with with the

steroid treatment of steroids, the steroid administration that's used for

treating, um treating other conditions.

So remember the role of cortisol.

So when you have too much cortisol being released you

will have a weight gain.

Um, and then also this sort of you have the

redistribution of fat into the abdominal areas, probably also because

you, um, it's considered as some sort of, um, um,

response to, to, to a stress.

So you needed some something to protect the core organs,

but most importantly, Cushing's syndrome or overproduction of cortisol is

related will trigger the, um, gluconeogenesis, which will cause too

much of glucose being released into the circulation.

And when there's too much glucose constantly in the circulation,

it will cause a condition called insulin resistance, which means

when you have an increase in glucose in the circulation,

the glucose will actually trigger the release of insulin from

the beta cells.

And these insulin will act on the insulin receptor to

actually allow the glucose transporters to be relocated to the

cells of, um, of adipose tissue or liver or muscles,

so that those cells can actually, um, sort of allow

the glucose from the circulation to, to gain entry.

But if you have a constant hyper secretion of insulin,

you will develop resistance to insulin.

So despite having a lot of insulin, the insulin receptors

won't actually work properly in response to, to to to

increase the plasma glucose.

And then they will actually, um, this will actually present

a sort of, uh, response from the other type of

cells in the, in the pancreas called alpha cells.

And these cells will release a glucagon, which will actually,

uh, sort of work to suppress insulin release.

So this whole process is how is presented exactly.

Like what would happen if a person has type two

diabetes, which is why with chronic stress and overproduction of

cortisol, you will have symptoms of type two diabetes and

the weight gain.

But then again, cortisol has a role in catabolism.

So you will have the loss of muscle and and

bone proteins.

And then they will also have effect on your immune

and inflammatory responses, where you will have reduced the wound

healing and and increase the bruising.

And these are all sorts of, um, uh, clinical sort

of presentation, uh, with people affected by the Cushing's syndrome.

Um, so this is a child that's being treated, um,

for the Cushing's syndrome.

And then after the overproduction of cortisol is being corrected,

he is able to sort of, um, go back to

his normal, um, sort of situation.

Um, that's all I have to say today,