Biosynthesis and action

Question 1

what are adrenal steroid hormones synthesised from

Answer 1

cholesterol

Question 2

What are the 2 sources of cholesterol. The main one?

Answer 2

cell stores - acetyl-CoA

mainly derived from plasma LDL

Question 3

What’s the rate-limiting step of steroidogenesis?

Answer 3

transport of cholesterol from the outer to the inner mitochondrial membrane

Question 4

Where is the first enzyme of steroidogenesis located?

Answer 4

inner mitochondrial membrane - initial side-chain cleavage of cholesterol

Question 5

What is cholesterol turned into?
What enzyme?**
What happens?

Answer 5

pregnenolone
enzyme = A = cholesterol 20,22 desmolase
made into pregnenolone to start zone specific steroid hormone synthesis

Question 6

What are the 3 parts of the cortex?

Answer 6

zona glomerulosa
zona fasciculata
zona reticularis

Question 7

What are the cells found in the medulla and what do they secrete?

Answer 7

chromatin cells

secrete - adrenaline, noradrenaline, dopamine, enkephalins and somatostatin

Question 8

What’s the main mineralocorticoid?

Answer 8

aldosterone

Question 9

Where is aldosterone made? Why is this place the only place that can make it?

Answer 9

made in zona glomerulosa

only one to contain aldosterone synthase enzyme

Question 10

What’s the pathway for aldosterone production?

Answer 10

mineralcorticoid pathway

Question 11

What is the main glucocorticoid?

Answer 11

cortisol (hydrocortisol)

Question 12

What enzyme is lacking in the zona glomerulosa?

Answer 12

enzyme F

Question 13

What 2 things are made at the zona reticularis? Why is it only made here?

Answer 13

DHEA and androstenedione (weak androgens)

zona fasciculata lacks cofactors for F* enzyme

Question 14

Broadly speaking, what do mineralocorticoids and glucocorticoids do?

Answer 14

Na+ retention

anti-inflammatory

Question 15

what’s the only hormone that regulates the HPA axis? What’s the consequence of this?

Answer 15

CORTISOL

excess levels of aldosterone and androgens can’t turn the system off

Question 16

what does aldosterone do? What stimulates its secretion?

Answer 16

act on DCT and CD to promote Na+ retention (water retention) and K+ elimination

stimulated by increased plasma [K+] and RAA (dependent on ACTH)

Question 17

What do the weak androgens do in females and males? What is it regulated by?

Answer 17

females - axillary and public hair growth, libido
neglible in men

regulated by ACTH (but cause no feedback)

Question 18

What can long term use of glucocorticoids cause?

Answer 18

down-regulate ACTH causing adrenal gland atrophy and Cushing’s disease

Question 19

What can dehydration trigger?

Answer 19

release of AVP (ADH) which stimulates ACTH

Question 20

CRH and AVP are synergistic – T/F?

Answer 20

TRUE - to elevate ACTH

Question 21

what is the role of the SCN in regulation of cortisol?

Answer 21

controls endogenous circadian rhythm

influences the hypothalamus which regulates cortisol further down the axis

Question 22

What’s the overall metabolic activity of cortisol? Go over the fine details

Answer 22

Metabolic effects
muscle and adipose- catabolic
liver- stimulate gluconeogenesis and glycogen storage

to elevate plasma glucose levels

Question 23

What does cortisol also do about glycogen?

Answer 23

build up glycogen stores

Question 24

Explain cortisol’s anti-inflammatory effects and immunosupressive effects– under what conditions?

Answer 24

At high physiological levels

• production of lipocortin 1 (inhibits PLA2)
• decrease T-lymphocytes
• decrease cytokines
• stabilises lysosomes
• decrease NO production