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Y2 Endocrine Block > Corticosteroid production and regulation > Flashcards

Corticosteroid production and regulation Flashcards

1
Q

What are steroids derived from?

A

Steroid hormones are derived from enzymatic modification of cholesterol

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2
Q

how is steroidogenesis regulated?

A

by controlling the enzymes which convert cholesterol into the steroid hormone

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3
Q

where are Enzymes which produce steroid hormones from cholesterol located?

A

in mitochondria and smooth ER

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4
Q

are steroid hormones stored after synthesis?

A

No, they are not stored but synthesized and immediately released

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5
Q

As steroid hormones aren’t water soluble, how are they carried in blood?

A

they are carried in the blood complexed to specific binding globulins.

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6
Q

what binding globulin carries cortisol?

A

Corticosteroid binding globulin

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7
Q

where are adrenal glands located?

A

in abdomen above kidneys

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8
Q

describe the size and colour of adrenal glands

A

Endocrine glands are 4-6cm

Yellow in colour due to high cholesterol

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9
Q

what are adrenal glands composed of?

A

Composed of outer cortex and inner medulla

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10
Q

how are the cortex and medulla adrenal glands different ?

A

Medulla is embryologically and histologically distinct to cortex, they are two different glands
Medulla- rich in blood + nerve supply
Cortex- consists of different zones

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11
Q

what is the arterial supply of adrenal cortex?

A

superior, middle and inferior suprarenal arteries

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12
Q

How does arterial blood flow and what vessel does it become?

A

moves towards the centre of the gland and flows into the medullary vein

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13
Q

describe the venous blood flow of the adrenal cortex?

A

Medullary vein emerges from the hilum before forming the suprarenal veins, which join the inferior vena cava on the right side and the left renal vein on the left

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14
Q

what is the adrenal nerve supply derived from? what do the nerves supply?

A

derived from the coeliac plexus and the thoracic splanchnic nerves.

The nerves supply the chromaffin cells of the adrenal medulla.

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15
Q

what surrounds the adrenal cortex?

A

Fibrous capsule

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16
Q

Name the 3 layers of the adrenal cortex

A

Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
SALT, SUGAR, SEX

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17
Q

describe the cell type in ZG, what hormone it secretes, what it is regulated by and what process it regulates

A

Cluster of small cells
Regulated by RAS and K+
Produces mineralocorticoids e.g. aldosterone, deoxycorticosterone.
Regulates Na+ homeostasis
Cluster of small cells with ball-like structure

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18
Q

describe the cell type in ZF, what hormone it secretes, what it is regulated by and what process it regulates

A

Column like cells
Regulated by ACTH
Produces Glucocorticoids e.g. cortisol, corticosterone
Regulates carbohydrate metabolism

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19
Q

describe the cell type in ZR, what hormone it secretes, what it is regulated by and what its role is

A

Haphazard cell arrangement
Regulated by ACTH
produces adrenal androgens e.g. DHEA, DHEA-sulphate

Sole source of androgens – (important in women as males has testes which make testosterone)

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20
Q

what is found in the medulla?

A

Chromaffin cells

And Numerous capillaries and veins – produces catecholamines like adrenaline

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21
Q

what is the Rate-limiting enzyme is cholesterol synthesis?

A

HMG-CoA reductase

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22
Q

in what form is cholesterol taken up by a cell?

A

in the form of low density lipoprotein (LDL).

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23
Q

what happens after LDL is taken into cells?

A

It is broken down into esterified cholesterol, and then free cholesterol – ready for steroid biosynthesis

24
Q

What is the first enzymatic step in steroid synthesis? what enzyme catalyses this reaction? where is it found?

A

the conversion of cholesterol to pregnenolone

Cytochrome P450 enzyme , found in inner mitochondrial membrane

25
Q

what is the rate limiting step? what is it carried out by?

A

the transport of free cholesterol from cytoplasm into mitochondria.

Carried out by Steroidogenic Acute Regulatory Protein (StAR) - which forms a channel to deliver cholesterol to inner mitochondrial membrane

26
Q

what is the name for the steroidogenic enzyme: Side-chain cleavage enzyme

A

CYP11A1

27
Q

what is the name for the steroidogenic enzyme: 3 beta-hydroxysteroid dehydrogenase

A

3 beta-HSD

28
Q

what is the name for the steroidogenic enzyme: 17 alpha-hydroxylase

A

CYP17

29
Q

what is the name for the steroidogenic enzyme: 21 hydroxylase

A

CYP21A2

30
Q

what is the name for the steroidogenic enzyme: 11 beta-hydroxylase

A

CYP11B1

31
Q

what is the name for the steroidogenic enzyme: Aldosterone synthase

A

CYP11B2

32
Q

what causes Congenital Adrenal Hyperplasia?

A

21 hydroxylase deficiency

33
Q

what type of receptors are steroid receptors?

A

Nuclear receptors

34
Q

What occurs at each domain of the steroid receptor

A

A/B: N terminal domain controls which gene is activated
C: DNA binding zone
D: hinge region- controls movement of receptor to nucleus
E: ligand binding domain
F: C-terminal domain

35
Q

describe the mechanism of action of steroid hormones

A

Steroid hormone diffuses through plasma membrane

Binds to intracellular cytosolic receptor

Receptor hormone complex enters nucleus and binds to DNA sequence

Binding initiates transcription to produce mRNA

mRNA is translated to protein which mediates cell response

36
Q

where are glucocorticoid receptors found?

A

widespread around body

37
Q

where are mineralocorticoid receptors found?

A

Distal CT of Nephron, Salivary glands, sweat glands, large intestine, also in brain, vascular tissue and heart

38
Q

why is cortisol more likely to bind to a mineralocorticoid receptor than aldosterone is to a glucocorticoid receptor?

A

Plasma Cortisol concentration is much higher than aldosterone

39
Q

what mechanism protects mineralocorticoid receptor from illicit occupation by glucocorticoids like cortisol?

A 
11 beta-HSDII catalyses the conversion of Cortisol (active) 
to Cortisone (inactive)  in selective tissues e.g. kidney
allowing aldosterone to function normally
40
Q

what inhibits the enzyme 11 beta HSD II?

A

Liquorice

41
Q

describe the effects of cortisol on the body

A 
Stimulates  gluconeogenesis in liver
stimulates lipolysis
permissive effect on glucagon
counteracts insulin 
increased skeletal muscle breakdown
immune suppression
42
Q

describe the mechanism of action of aldosterone

A

Upregulates epithelial sodium channel which increases Na and water reabsorption

Stimulates secretion of K into lumen and secretion of H+ via the H/ATPase in intercalated cells of cortical collecting tubules

43
Q

describe the role of hypothalamus and anterior pituitary in regulation of cortisol production

A

Hypothalamus secretes Corticotropin releasing Hormone, which causes Anterior Pituitary to release Adrenocorticotropic hormone (ACTH) which acts on Adrenal cortex to cause cortisol production

44
Q

at what time of day are cortisol levels higher?

A

In the morning

45
Q

What is POMC (propriomelanocortin), in the anterior pituitary, made of? and what does it control

A

ACTH
Lipotropin

which become:
Beta endorphin
Melanocyte Stimualting hormone

Controls melanin pigmentation (increase ACTh = increase MSH= increase melanin so dark skin)

46
Q

what type of receptor is ACTH receptor?

A

G-protein Coupled Receptor

47
Q

after ACTH binds to G-protien coupled receptors what happens?

A

Conformation changes in receptor stimulate adenyl cyclase , causing an increase in cAMP, activation
of PKA and calcium influx

48
Q

what rapid and long term effects does ACTH have to increase cortisol production?

A

Stimulation of cholesterol delivery to the mitochondria (rapid) -for steroidogensis

Increased transcription of genes coding for steroidogenic enzymes (long-term).

49
Q

what activates the RAS system?

A

Activated in response to low blood pressure, plasma sodium

50
Q

how does Angiotensin II increase aldosterone production?

A

AngII binds to 7 transmembrane domain G-protein coupled receptor

Activates phospholipase C

Cascade of reactions causes Ca2+ release

this stimulates transcription of StAR and cholesterol uptake into mitochondria

51
Q

how does potassium increase aldosterone production?

A

Increase in potassium, increases aldosterone

52
Q

what is primary aldosteronism and what are the most common causes of it?

A

High levels of Aldosterone

Most Common Causes:
Aldosterone producing adenoma (unilateral)
Bilateral adrenal hyperplasia

53
Q

what effects does primary aldosteronism have?

A 
Increased sodium reabsorption, 
Volume expansion
Hypokalaemia (Potassium excretion)
Alkalosis (due to hydrogen excretion)
Low PRA (plasma renin activity)
Hypertension
54
Q

what is cushing’s syndrome and what are the most common causes of it?

A

High levels of Cortisol

Caused by:
ACTH producing adenoma (pituitary)
Cortisol producing adenoma (adrenal)
Iatrogenic – caused by large doses of steroids for other medical conditions

55
Q

in Addison’s disease, there is the inability to make _____ and _____

A

cortisol and aldosterone

Y2 Endocrine Block (21 decks)

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