Adrenal cortex

Where are the adrenal glands found and how many are there

2

Sit at apical pole of kidney

What is found in the adrenal gland medulla?

Chromaffin cells

Produce adrenaline and noradrenaline

What are the 3 cells called found in the cortex of the adrenal gland (outside → inside)

glomerulosa, fascicular, reticularis

Function of cells found in adrenal gland cortex

produce corticosteroids

What are corticosteroids generated from?

cholesterol

structure of the adrenal glands

inside - medulla

outside - cortex formed of 3 types of cells

glomerulosa produces…

mineralocorticoids

fasciculata produces…

glucocorticoids

reticularis produces…

androgen and oestrogens

describe synthesis of adrenal steroids

note - cholesterol is not stored in cells (only its precursors)

cholesterol transported with LDL and absorbed from the GI tract

cholesterol synthesised from acetate

How does steroid action occur?

* Cytoplasmic receptors present in target tissues
* Steroid binds
* Receptors translocate to the nucleus
* Gene transcription modulated to produce biological effects within the cell

How do glucocorticoids circulate?

Bound to plasma proteins

Half life of glucocorticoids

60-90 mins

What controls the release of glucocorticoids?

* Tropic hormones of hypothalamus/pituitary organ
* Circadian release

what stimulates release of glucocorticoid from adrenal cortex and how?

* Acute and long-term stress


* Hypothalamic circadian rhythm generator


1. Above stimuli cause the release of CRH (corticotrophin releasing hormone) which enters anterior pituitary
2. Stimulates corticotrophs to release ACTH (adrenocorticotrophic hormone)
3. ACTH enters into circulation and binds to receptor on Fasciculata Cells in adrenal cortex
4. Stimulation of glucocorticoids which enter into circulation and affect peripheral tissues target cells

Factors which inhibit release of glucocorticoid from adrenal cortex

* cortisol levels inhibit ACTH and CRH release
* ACTH can negatively feedback to regulate CRH production

How can glucorticoids affect metabolism?

* Carbohydrate metabolism
* Stimulation of gluconeogenesis
* Gluconeogenesis = glucose synthesis from amino acids
* Inhibit insulin effects = decrease tissue uptake of glucose
* Protein metabolism
* Stimulation of protein catabolism → releases aas for gluconeogenesis
* Gluconeogenesis = glucose synthesis from amino acids
* Fat metabolism
* During stress/starvation, metabolism shifts from glucose to fat
* = increased lipolysis (fatty acids used as fuel – glucose sparing)
* All above lead to hypoglycaemic conditions

How do glucocorticoids affect cardiac, skeletal and vascular smooth muscle?

Insufficiency of glucocorticoids = muscle fatigue, mechanism undefined

* Cardiac – cardiac insufficiency/failure
* Vascular – loss of vasomotor tone
* Skeletal – general muscle weakness

How do glucocorticoids affect the nervous system

* Effects on mental function
* Insufficiency of glucocorticoids – lethargy, apathy, inability to concentrate
* Excess of glucocorticoids – hyperactivity, insomnia, euphoria, increased sensory acuity

How do glucocorticoids respond to stress?

Metabolism

* Increase in metabolic fuel for escape

Cardiac, skeletal and vascular smooth muscle

* Muscle primed for escape

Nervous system

* Alertness

How are glucocorticoids used in inflammatory and immune response?

Inflammatory and immune response

* Anti-inflammatory and immune-suppressive
* Inhibit cytokine secretion
* Inhibit immune cell proliferation (less immune cells present to cause immune response)
* Inhibit antibody synthesis
* Increase susceptibility to infection
* Therapeutic use of glucocorticoids
* Synthetics produced for anti-inflammatory properties

Half life of mineralocorticoids

15-30 mins

Function of mineralocorticoids

Regulate Na+ and K+ concentration in extracellular fluid

Secretion stimuli for mineralocorticoids

Changes in electrolyte levels and water balance

How are mineralocorticoids released?

Juxtaglomerular cells release renin in response to

* Low blood pressure
* Low Na+
* Low blood volume

Renin acts on angiotensinogen released from liver to produce angiotensin 1

Angiotensin 1 converted into angiotensin 2 by angiotensin converting enzyme in the lungs and kidney

Angiotensin 2 binds to glomerulosa cells in the adrenal cortex stimulating release of aldosterone (a type of mineralocorticoid)

Function of mineralocorticoids

Aldosterone (example of mineralocorticoids) act on kidney tubules to activate Na/K pumps

* Increase Na+ retention
* Increase K+ excretion
* Resets blood volume and pressure

What is hypercorticism

Overproduction of cortisol

What is another name for Cushing’s Disease?

Hypercorticism

Cause of primary hypercorticism

Adenomas (cancers) of the adrenal cortex

Cause of secondary hypercorticism

pituitary tumours which cause uncontrolled levels of ACTH production resulting in high cortisol levels

Cause of latrogenic hypercorticism

widespread use of synthetic glucocorticoids

Symptoms of hypercorticism

Upper body obesity, rounded face, increased neck fat, slender extremities, fragile/thin skin, weak bones, hyperglycaemia

Therapeutic used of glucorticoids

* Anti-inflammatory and anti-allergic effects
* Used as an immunosuppressant

risk of therapeutic use of glucorticoids

* Can cause Latrogenic hypercorticism
* Withdrawal must be done carefully to avoid hypocorticism (negative feedback on endogenous cortisol)
* Synthetic cortisol results in less production of cortisol

What is Addison’s disease?

Hypoadrenocorticism

What is hypoadrenocorticism?

Under secretion of glucocorticoids and mineralocorticoids

Cause of primary hypoadrenocorticism

Atrophy of adrenal cortex due to autoimmune attack

* ACTH levels are high, no steroid to provide negative feedback

Cause of secondary hypoadrenocorticism

Pituitary malfunction (reduced ACTH release affects cortisol, but aldosterone is still produced)

Cause of latrogenic hypoadrenocorticism

Due to abrupt withdrawal of steroid therapy

Symptoms of hypoadrenocorticism

* Muscle weakness
* Poor cardiovascular function
* Low blood pressure (lack of gluco- and mineralocorticoids

Effects of low cortisol on other hormones

* no negative feedback of CRH and ACTH
* CRH and ACTH increase

Where are catecholamines produced and secreted?

produced - chromaffin cells

secreted - adrenomedullary cells

Synthesis of catecholamines

* Adrenal medulla is a primary source of adrenaline
* Noradrenaline is synthesized by chromaffin cells and noradrenergic neruons
* Catecholamines stored in granules within chromaffin cells ready to be released on demand

example of a catecholamine

adrenaline, noradrenaline

Secretion of catecholamines

* Under control of SNS


1. Release of Ach
2. Ach binds to N2 receptors on chromaffin cell
3. Depolarisation of cell
4. Calcium influx
5. Granules fuse with cell membrane and catecholamine released into extracellular fluid

Regulation of adrenergic receptors occurs by…

* Hormone binding properties (affinity)
* Receptor concentration
* Receptor signalling – G-protein coupled receptors
o Activation of second messengers

3 effects of release of catecholamines in response to stress

* Vasoconstriction in viscera and skin
* Dilation of coronary arteries and vessels in skeletal muscle
* Glycogenolysis
* Increased force and rate of constriction of the heart

How does hyper function of adrenal medulla occur, and what are the effects?

* Pheochromocytomas: tumours arising from chromaffin cells
* Rare, benign, secrete large quantities of catecholamines
* Result in elevated blood pressure and increased heart rate