8 adrenal function

Question 1

what are adrenal steroid hormones derived from and how?

Answer 1

cholesterol

by sequential, enzymatic- mediated modification of the structure

• some from cell stores- synthesised from acetyl CoA
• mainly derived from plasma LDL

Question 2

what is the rate limiting step in steroidogenesis

Answer 2

transport of cholesterol from outer to inner mitochondral membrane

Question 3

where is the first enzyme in steroidogensis located and what does it do?

Answer 3

inner mitochondrial membrane

initial side chain cleavage of cholesterol to give pregenolone

Question 4

zone specific steroidogenesis: what is this?

what do the cortical zones secrete

Answer 4

differential expression of biosynthetic enzymes in different zones of adrenal cortex:

zona glomerulosa: mineralocorticoids

zona fasiculata: glucocorticoids and gonadocorticoids

zona reticularis: glucocorticoids and gonadocorticoids (androgens)

Question 5

key points of zona glomerulosa

Answer 5

lacks 17a hydroxylase (enzyme F)

contains aldosterone synthase (enzyme E) -> produces aldosterone

Question 6

Zona fasciculata and zona reticularis key points (enzymes)

Answer 6

Enzyme F (CYP17) has two activities:

F 17a-hydroxylase

F* 17,20-lyase

Zona fasciculata lacks cofactors for F* activity

ZF produces cortisol

ZR produces weak androgens (testosterone, oestrone, oestradiol and oestriol)

Question 7

Answer 7

Question 8

Answer 8

Question 9

Hypothalamus - pituitary- adrenal HPA axis

Answer 9

Question 10

functions of aldosterone

what is secretion stimulated by

Answer 10

main mineralocorticoid

• Na+ retention (→ water retention) and K+ elimination in LDCT and CCD principal cells
• Secretion stimulated by increased plasma [K⁺], and renin-angiotensin system (largely independent of ACTH).

Question 11

functions of androgens

• name
• release (women and men)
• regulation

Answer 11

Dehydroepiandrosterone (DHEA), DHEAS (sulphated DHEA) and androstenedione

• age-related release: surge in puberty and peaks 20-25 years

= 50% in women (axillary/ pubic hair growth and libido)

= neglible contribution in men

• Regulated by ACTH (and other unknown factors), but no feedback on CRH/ ACTH

Question 12

what is the steroidal activity of cortisol?

what controls cortisol secretion?

Answer 12

• glucocorticoid with mineralocorticoid activity
• suprachiasmatic nucleus SCN- controls endogenous circadian rhythms

Question 13

what type of stressors stimulates the hypothalamus to secrete cortisol?

Answer 13

emotional: anxiety, fear
physiological: pain, fever, hypoglycaemia, injury, fluid deprivation, surgery

AVP is also stimulated in stress

CRH and AVP act synergistically to elevate ACTH levels

Question 14

how do steroid hormones act in the cell?

Answer 14

via intracellular receptors, act as hormone regulated transcription factors: bind onto promoter region

some more rapid non-genomic actions mediated by membrane or cytosolic receptors

Question 15

actions of cortisol

Answer 15

• Metabolic effects
• Anti-inflammatory/ immunosuppressive effects
• Role in adaptation to stress
• Permissive role in action of other endocrine hormones
• Actions on other tissues

Question 16

what are the metabolic effects of cortisol

muscles

adipose tissue

liver

Answer 16

muscle and adipose tissue: catabolic

liver : stimulate gluconeogenesis, and glycogen storage

overall elevates plasma glucose levels

Question 17

stress adaptation in acute and chronic stress

Answer 17

acute: behavioural and psychological changes-> executive function-> then rest and recovery
chronic: behavioural and psychological changes-> long term physiological dysregulation-> reduced perfomance and health (mental and physical)

Question 18

Anti-inflammatory/ immunosuppressive effects of cortisol

Answer 18

1. Stimulate production of lipocortin 1 (annexin1) – inhibits PLA2 (enzyme that generates arachidonic acid the precursor for prostanoids & leukotrienes)
2. Decrease number and activation of T-lymphocytes
3. Decrease production of cytokines (interleukins, TNF-a)
4. Stabilises lysosomes
5. Decrease NO production

Question 19

uses of glucocorticoids analogues

eg. prednisolone, dexamethasone

Answer 19

anti inflammatory conditions eg. asthma

immunosuppression: organ transplantation

replacement therapy: addision’s disease

pre term labour (enhance feotal lung maturation)

Question 20

where are the steroids transferred to during its biosynthetic pathway?

Answer 20

different subcellular compartments- eg. inner mitochondria membrane and SER

Question 21

what is the typical diurnal variation of plasma cortisol?

Answer 21

peak in morning, trough in late evening