8 adrenal function Flashcards
what are adrenal steroid hormones derived from and how?
cholesterol
by sequential, enzymatic- mediated modification of the structure
- some from cell stores- synthesised from acetyl CoA
- mainly derived from plasma LDL
what is the rate limiting step in steroidogenesis
transport of cholesterol from outer to inner mitochondral membrane
where is the first enzyme in steroidogensis located and what does it do?
inner mitochondrial membrane
initial side chain cleavage of cholesterol to give pregenolone
zone specific steroidogenesis: what is this?
what do the cortical zones secrete
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)
key points of zona glomerulosa
lacks 17a hydroxylase (enzyme F)
contains aldosterone synthase (enzyme E) -> produces aldosterone
Zona fasciculata and zona reticularis key points (enzymes)
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)
Hypothalamus - pituitary- adrenal HPA axis
functions of aldosterone
what is secretion stimulated by
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).
functions of androgens
- name
- release (women and men)
- regulation
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
what is the steroidal activity of cortisol?
what controls cortisol secretion?
- glucocorticoid with mineralocorticoid activity
- suprachiasmatic nucleus SCN- controls endogenous circadian rhythms
what type of stressors stimulates the hypothalamus to secrete cortisol?
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
how do steroid hormones act in the cell?
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
actions of cortisol
- Metabolic effects
- Anti-inflammatory/ immunosuppressive effects
- Role in adaptation to stress
- Permissive role in action of other endocrine hormones
- Actions on other tissues
what are the metabolic effects of cortisol
muscles
adipose tissue
liver
muscle and adipose tissue: catabolic
liver : stimulate gluconeogenesis, and glycogen storage
overall elevates plasma glucose levels
stress adaptation in acute and chronic stress
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)
Anti-inflammatory/ immunosuppressive effects of cortisol
- Stimulate production of lipocortin 1 (annexin1) – inhibits PLA2 (enzyme that generates arachidonic acid the precursor for prostanoids & leukotrienes)
- Decrease number and activation of T-lymphocytes
- Decrease production of cytokines (interleukins, TNF-a)
- Stabilises lysosomes
- Decrease NO production
what is the typical diurnal variation of plasma cortisol?
peak in morning, trough in late evening
