The adrenal gland (lecture 28)

Question 1

Anatomy of the adrenal gland

Answer 1

Encased in fat tissue 
They weigh about 8-10g 
Composed of 2 different types of tissue that produce different hormone types 
Inner part = medulla 
Outer part = cortex

Question 2

Anatomy of the medulla

Answer 2

Comprises 10-12% of adrenal weight

Major product is epinephrine

Composed of neuronal tissue & has potential to become the postsynaptic cell for the sympathetic nervous system

Question 3

Anatomy of the cortex

Answer 3

Comprises 80-90% of adrenal weight & has 3 distinct zones

Zona reticularis
Zona fasiculata
Zona glomerulosa

All produce steroid hormones but just different types and amounts

Question 4

What is the zona reticularis?

Answer 4

10%
Inner section

Compact cells with less lipid

Produce cortisol & androgens
Generally more androgens

Question 5

What is the zona fasiculata?

Answer 5

75%
Middle section

Large lipid containing cells

Produce cortisol & androgens
Generally more cortisol

Question 6

What is the zona glomerulosa?

Answer 6

15%
Outer section

Produces aldosterone

Question 7

What is the capsule?

Answer 7

Fibrous layer around the outside

Question 8

Why does the zona glomerulosa not produce androgens and cortisol?

Answer 8

Lacks 17 alpha-hydroxylase - enzyme is missing

Blocks pathway to form androgens & cortisol

Question 9

Function of aldosterone

Answer 9

Major mineralocorticoid – controls water & sodium balance
50-70% bound to albumin in plasma

Primary action on kidney, colon & salivary glands to maintain normal Na+ concentration & extracellular fluid volume

Binds to mineralocorticoid receptors within principal cells (cell type in the nephron)

Upregulates EnaC
Upregulates & activates Na+/K+ ATPase

Question 10

How is Na+ absorption different with and without aldosterone?

Answer 10

With aldosterone > 99.6%
Without = 98%

Difference = 3.5L of fluid per day

Question 11

What is aldosterone release triggered by?

Answer 11

Low blood pressure

Causes the kidney to release renin

Question 12

How does low blood pressure cause aldosterone release?

Answer 12

Renin modifies angiotensinogen to form angiotensin I
ACE converts angiotensin I to angiotensin II – cutting off a couple of amino acids
Angiotensin II does a lot of things
• Acts in the kidneys to cause vasoconstriction
• Acts in the cardiovascular control centre
• Acts in the hypothalamus
• Acts in the adrenal cortex – stimulates aldosterone production to increase sodium absorption

Question 13

How is cortisol produced?

Answer 13

Hypothalamus responds to stress by releasing CRH (cortitrophin releasing hormone)

Acts on the corticotrophs in the anterior pituitary

They will then release ACTH – adrenal corticotrophic hormone – enters the circulation and acts on the cortex of the adrenal gland resulting in cortisol production

Question 14

What is the function of ACTH?

Answer 14

1. ACTH binds to receptor
2. Activates adenyl cyclase
3. Produces cAMP which activates PKA
4. PKA phosphorylates other molecules to activate them & change their function

Question 15

What does PKA do after being activated by ACTH?

Answer 15

• Increase hydrolase of cholesterol ester – gets it out of its storage form to free cholesterol
• Increased transcription of enzymes needed for steroid synthesis
• stAR protein – takes free cholesterol into the mitochondria – rate limiting step
• P450scc (side chain cleavage) cleaves the side chain of cholesterol to allow further modification to produce the steroid hormone

Question 16

Why can the zona fasiculata & reticularis not produce aldosterone?

Answer 16

lack CYP11B2 gene (P450aldo)

Lacks the enzyme to produce aldosterone

Can only produce cortisol or adrenal androgens

Question 17

What is cortisol?

Answer 17

Major glucocorticoid – role in glucose homeostasis

> 90% bound to plasma proteins – don’t like being in water so have to be bound to travel round body

half life = 60-90 minutes

Effects virtually all tissues mainly by binding to its receptor & controlling gene transcription

Question 18

Effects of cortisol

Answer 18

• stimulates hepatic gluconeogenesis
• inhibits glucose uptake in muscle & adipose tissue
• stimulates muscle catabolism – breakdown of muscle
• inhibits bone formation
• leads to loss of collagen & connective tissue – thinning of skin if too much
• increases vascular sensitivity to epinephrine & norepinephrine
• can modulate behaviour & cognitive function
• inhibits gonadal release of testosterone, oestrogen & progestins

Question 19

How does cortisol act as a anti-inflammatory & immunosuppression?

Answer 19

inhibits cytokine production & thus T cell proliferation

inhibits prostoglastin & leukotriene production

helps keep the immune system in balance

Question 20

How does cortisol inhibit prostoglastin & leukotriene production?

Answer 20

1) Phospholipids broken down to arachidonic acid by phospholipase A2
• Produces prostaglandins & leukotrienes

2) Cortisol increases production of lipocortin-1 which inhibits phospholipase A2
• Stop productions of arachidonicacid
• Also decreases activity of cyclooxygenase that converts arachidonic acid to prostogladins & leukotrienes

3) Decreases inflammation