Adrenal function and disorders Flashcards
What are adrenal steroid hormones derived from and how
CHolesterol
-By sequential, enzymatically-mediated modification of the structure
Where is cholesterol that is used to form adrenal steroid hormones derived from
Mainly Plasma LDL
Some from cell stores (synthesised from acetyl CoA)
What is the rate limiting step in steroidogenesis
Transport of cholesterol from the outer to the inner mitochondrial membrane
What is the first step in steroidogenesis and name the enzyme involved and its location
First enzyme is located in inner mitochondrial membrane
- There is initial side-chain cleavage of cholesterol.
- Cholesterol 20,22 desmolase turns cholesterol (C-27) into pregnenolone (C-21)
In the adrenal gland, what does the zona glomerulosa mainly produce
Mineralocorticoids
IN the adrenal gland, what does the zona fasiculata mainly produce
(Mainly) Glucocorticoids
and gonadocorticoids
IN the adrenal gland, what does the zona reticularis mainly produce
Glucocorticoids and gonadocorticoids
What are the zones in the adrenal gland going from the capsule end to the medullary end
Capsule- Zona glomerulosa
Zona fasciculata
Zona reticularis
What does pregnenolone
It is a common precursor to the specific zones in the adrenal gland. There is zone specific steroid hormone synthesis and all areas produce different things but pregnenolone is used by all at first
Where does each steroid go as it progresses along its biosynthetic pathway
Between 2 sub cellular compartments
What is the action of mineralocorticoid activity
Na+ retention
What is the action of glucocorticoid activity
Anti- inflammation
What is is cortisol activity effective as
Equally asa mineralocorticoid and glucocorticoid
What is aldosterone effective as
Mineralocorticoid
What hormone regulates the endocrine axis only
Cortisol (ACTH and CRH release)
What is the role of aldosterone and what is it
Mineralocorticoid
Principally act on DCT and collecting ducts of kidney to promote NA+ retention and so H20 retention and K+ elimination during formation of urine
What is the secretion of aldosterone stimulated by
Increased plasma [K+] and renin angiotensin system ( largely independent of ACTH)
What are androgens
DHEA/DHEAS and androstenedione
How do androgen levels change with age
Starts at 6/7 yo. Peaks at 20-25 and decreases as person gets older
How do androgens affect women and men
50% in women - contribute to axillary/pubic hair growth and libido
Negligible contribution in men
What are androgens regulated by
ACtH but no feedback on CRH/ACTH
What is the main glucocorticoid
Cortisol
What happens when there is a stress stimulus
Activation of hypothalamus to release CRH
CRH acts on anterior pituitary which releases ACTH
This increases action of adrenal cortex to release cortisol
when is the action of ADH stimulated
When the person is under stress such as when there is fluid deprivation
How does ADH affect cortisol levels
Increases stimulation to anterior pituitary which increases ACTH levels and so this increases action of adrenal cortex and therefore cortisol
How are steroid hormones transported in the circulation
Bound to plasma proteins
What are the actions of cortisol
Metabolic effects
Antiimflammatory/immunosuppressive effects
Role in adaptation to stress
what are the metabolic effects of cortisol
In muscle and adipose tissue (catabolic which means breakdown)
IN liver- Stimulate glujconeogenesis and glycogen storage to elevate plasma glucose levels
How does cortisol affect muscle
Decrease glucose uptake via insulin mediated GLUT4
Increase protein breakdown
Decrease protein synthesis
How does cortisol affect adipose tissue
Decrease glucose uptake (insulin mediated via GLUT4)
Increase lipolysis
Decrease lipogenesis
What do the actions of cortisol on muscle and adipose tissue do to allow the liver to help with the actions of cortisol
Once cortisol has acted on adipose tissue and muscle, there are more free fatty acids and glycerol from adipose tissue and more amino acids from muscle which go to the liver and so there is increased gluconeogenesis and increased glycogen synthesis
What does cortisol do to glycogen stores
Increases them. Does this by turning excess glucose into glycogen in case the stressful situation occurs again as it is a readily- accessible source of glucose
How does cortisol have an anti-inflammatory/immunosuppressive effect
-It stimulates the production of Annexin1 which inhibits PLA2 (an enzyme that generates arachidonic acid which is the precursor for prostanoids and leukotrienes)
- Decrease number and action of T lymphocytes
- decrease production of cytokines
- Stabilises lysosomes
- Decrease NO production
