Lecture 9 - ACTH and Glucocorticoids- the regulators of stress responses

Question 1

HPA axis: what is it, what do each of the parts release, and what do these secreted hormones do?

Answer 1

Hippocampus - pituitary gland - adrenal gland

The hippocampus releases corticotrophin-releasing hormone (CRH) which activates the pituitary gland

Pituitary gland - releases adrenocorticotrophic hormone which activates the adrenal gland

Adrenal gland - releases cortisol which affects the body

Question 2

Glucocorticoids: what is an example of a difference between humans and rats/mice?

Answer 2

• Cortisol in humans
• Corticosterone in rats and mice

Question 3

Hypothalamus/pituitary pictures

Question 4

Hormones produced by the adrenal gland: where are they produced, what are the types, and what are examples of them?

Answer 4

Cortex:
* Glucocorticoids - cortisol
* Mineralocorticoids - aldosterone
* Sex steroids - testosterone/oestrogen

Medulla:
* Epinephrine
* Norepinephrine

Question 5

Glucocorticoid effects: liver, adipose tissue, muscle, immune system, bone, brain, cardiovascular system, kidney, skin, and fetus

Answer 5

• Liver - Increases blood glucose - stimulates gluconeogenesis and glycogenolysis
• Adipose tissue - increase lipolysis
  which go to the liver
• Muscle - decreases protein synthesis and increases protein metabolism
• Immune system - anti-inflammatory and immunosuppressive effects
• Bone - decrease osteoblasts and stimulate bone resorption
• Brain - affect memory and sleep patterns and mood
• CV system - increase blood pressure and cardiac output
• Kidney - increase water diuresis and glomerular filtration rate, minor effect on sodium retention and potassium
  excretion
• Skin - inhibit keratinocyte proliferation and
  differentiation and reduce sebum production
• Fetus - required for organ maturation particularly the lung

Question 6

Glucocorticoids: what are their effects on the liver?

Answer 6

Liver - Increases blood glucose - stimulates gluconeogenesis and glycogenolysis

Question 7

Glucocorticoids: what are their effects on the adipose tissue?

Answer 7

Adipose tissue - increase lipolysis
which go to the liver

Question 8

Glucocorticoids: what are their effects on the muscles?

Answer 8

Muscle - decreases protein synthesis and increases protein metabolism

Question 9

Glucocorticoids: what are their effects on the immune system?

Answer 9

Immune system - anti-inflammatory and immunosuppressive effects

Question 10

Glucocorticoids: what are their effects on the bones?

Answer 10

Bone - decrease osteoblasts (inhibiting bone formation) and stimulate bone resorption

Question 11

Glucocorticoids: what are their effects on the brain?

Answer 11

Brain - affect memory and sleep patterns and mood

Question 12

Glucocorticoids: what are their effects on the cardiovascular system?

Answer 12

CV system - increase blood pressure and cardiac output

Question 13

Glucocorticoids: what are their effects on the kidneys?

Answer 13

Kidney - increase water diuresis and glomerular filtration rate, minor effect on sodium retention and potassium
excretion

Question 14

Glucocorticoids: what are their effects on the skin?

Answer 14

Skin - inhibit keratinocyte proliferation and
differentiation and reduce sebum production

Question 15

Glucocorticoids: what are their effects on the fetus?

Answer 15

Fetus - required for organ maturation particularly the lung

Question 16

Gluconeogenesis

Answer 16

Producing glucose from non-carbohydrate sources (proteins etc)

Question 17

Glycogenolysis

Answer 17

Breaking down glycogen into glucose

Question 18

Lipolysis

Answer 18

Metabolic process that breaks down fat stores into energy-rich fatty acids and glycerol

Question 19

Water diuresis

Answer 19

Increased urine flow caused by decreased reabsorption of solute-free water in the collecting ducts

Question 20

Mechanisms controlling the HPA axis

Answer 20

• Circadian - ACTH/cortisol vary on time
• Pulsatile -
• Stress - promotes CRH release

Question 21

Circadian rhythm: what is it, how is it different to a diurnal rhythm, and how can it be related to the HPA axis

Answer 21

The natural 24-hour cycle of physical, mental, and behavioural changes that occur in the body

Diurnal rhythm - 24-hour cycle synchronized to and dependent on an external cue
Circadian rhythm - 24-hour cycle based on internal, cyclic events (synchronised to but not dependent on an external cue)

Diurnal Rhythm - ACTH and cortisol levels are highest at ~06.00 and lowest at ~12:00

Question 22

Pulsatile control of HPA axis hormones

Answer 22

Episodes of release last from 1 to 3 hours.
* 7 to 8 episodes per 24 hours.
* They are not evenly distributed, there are fewer episodes at night.
* Reason for episodic release of ACTH and cortisol is not clearly understood but recent computational modelling suggests timeframe of molecular events controls it

Question 23

HPA axis negative feedback

Answer 23

Cortisol inhibits the secretion of ACTH from the pituitary as well as CRH from hippocampus

Question 24

Factors controlling the HPA axis

Question 25

CRH:

Answer 25

Corticotrophin Releasing Hormone

Synthesised by hypothalamus.
* Very much smaller amounts found in skin, immune
cells and adrenal.
* Function of peptide in these tissues is not clear
Structure: 41 amino acid peptide
First identified in 1981
Function: Stimulates ACTH synthesis
Levels: What matters is levels getting to pituitary
Levels in blood - not of much value
Receptors:
* CRH-R1 and CRH-R2
* CRH-R1 accounts for all HPA activity as evidenced by
mice with targeted deletion of CRH-R1

Question 26

Multiple levels of Regulation
of ACTH production

Answer 26

(Pro-opiomelanocortin) POMC GENE - mRNA - protein - ACTH