Week 4. HPA axis

Question 1

What are the effects of glucocorticoids?

Answer 1

• reduced immune response and inflammation
• increase in depression and anxiety
• reduced growth and reproduction
• increased gluconeogenesis, lipolysis, proteolysis

Question 2

Outline the production of CRH.

Answer 2

• stimulation is via neuronal input into the hypothalamus.
• adenyl cyclase activated –> cAMP dependent PKA
• PKA phosphorylates cAMP regulatory element binding (CREB) protein –> binds to CHR promotor –> increased mRNA expression - more protein

Question 3

What are the three categories of the stress response?

Answer 3

1. Behavioural
2. Autonomic, sympathetic nervous
3. Endocrine

Question 4

What is bioavailability regulation and how is it achieved?

Answer 4

The tissue can regulate how much of the GC is active.

11β – HSD2 –> enzyme that inactivates GC

Question 5

How can less CRH be produced and what is the type of hormone released?

Answer 5

• reversing the pathway reduces amount of CRH being produced

- pre pro ACTH (adenocorticotropic hormone) is released

Question 6

What is the pathway of cortisol production?

Answer 6

POMC + CRH (anterior pituitary) –> ACTH –> MC2R receptor –> cAMP dependent PKA –> CREB protein –> mRNA translation –> protein –> cholesterol –> cortisol

Question 7

How is the stress response dampened down and regulated?

Answer 7

Negative feedback

Question 8

What does HPA stand for?

Answer 8

Hypothalamic pituitary adrenal

Question 9

What is this axis responding to?

Answer 9

Stress

Question 10

Describe the adenylate cyclase pathway.

Answer 10

• produces ACTH
• precursor CRH –> CRH via stimuli
• hormone interacts with complementary receptor –> hormone in cell produces enzymes (effect)
• happens very quickly

Question 11

What is the difference between cortisol and corticosterone?

Answer 11

• cortisol is the most abundant endogenous GC in humans.

- Corticosterone is the inactive form of cortisol

Question 12

What are the names of the two types of CRH receptor and what is their function?

Answer 12

1. CRH-R1
   - found in pituitary anterior lobe (PAL)
   - allows PAL to make ACTH
2. CRH-R1
   - CRH-R2a –> exclusively in brain
   - CRH-R2b –> heart and skeletal muscle

Question 13

What is this axis also known as?

Answer 13

Glucocorticoid axis

Question 14

Describe the behavioural stress response.

Answer 14

The conscious response, like fear and anxiety

Question 15

What is POMC?

Answer 15

Pro opiomelanocortin is a precursor peptide with 241 amino acids. It can be cleaved to produce ACTH.

Question 16

Describe the two types of glucocorticoid receptor?

Answer 16

• glucocorticoid receptor –> periphery and brain
• mineralcorticoid receptor (binds aldesterone) –> heart and kidneys
• MR has 10x the affinity of GR
• -> MR is used when GC levels are very low, and in times of stress GR is used

Question 17

What is CRH made from and where is it released?

Answer 17

A 41 amino acid neuropeptide. Made in the hypothalamus, involved in all three steps of the stress response

Question 18

What does ACTH production ultimately depend on?

Answer 18

• the activation of prohormone convertase, which allows for post translational processing of CRH.

Question 19

What are the effects of CRH?

Answer 19

• endocrine response –> production of adenocorticotrophic hormone
• fear and anxiety
• GI tract: increased motility
• reduced immune response
• fertility inhibitor

Question 20

What is CRH?

Answer 20

Corticotropin releasing hormone

Question 21

Name the two most abundant glucocorticoids.

Answer 21

Cortisol and corticosterone

Question 22

Describe the autonomic response.

Answer 22

Controls sympathetic nervous response, like increased heart rate and ventilation

Question 23

Describe the endocrine response.

Answer 23

Provides fuel for the autonomic response