Corticotrophin-releasing hormone (paraventricular nucleus)
Hypothalamus · CRH AVP co-secreted Diurnal
Parvocellular neurones of the paraventricular nucleus secrete CRH into the portal blood, with vasopressin as a co-secretagogue that markedly potentiates the corticotroph. Output is pulsatile and diurnal.
Detail
- Releases
- CRH (41 amino acids) plus AVP; CRH acts on the corticotroph through a Gs-coupled receptor
- Rhythm
- ACTH and cortisol peak in the hours before waking (about 6-8 am) and trough near midnight; the overnight 1 mg dexamethasone test exploits this
- Stimuli
- Physical and psychological stress, hypoglycaemia, hypotension, surgery, IL-1 and IL-6
- Inhibited by
- Cortisol on the long loop and ACTH on the short loop
When it goes wrong
Prednisolone above about 5 mg daily for more than three weeks
CRH and ACTH suppressed with adrenal atrophy; abrupt withdrawal or intercurrent illness precipitates adrenal crisis, so taper and give stress cover
Depression, alcohol excess, obesity or shift work
Pseudo-Cushing: cortisol fails to suppress on the 1 mg dexamethasone test with no pituitary or adrenal tumour
Practise this structure
2 questions in the bank tagged Feedback Axis.
A 35-year-old woman has palpitations and a 9 kg weight loss over 3 months. Her free thyroxine is 48 pmol/L (reference 10–22 pmol/L), TSH is less than 0.01 mIU/L…
Mechanisms of disease · common
A 41-year-old woman has progressive weight gain, proximal muscle weakness and easy bruising. Her 24-hour urinary free cortisol is 780 nmol/day (reference less t…
Mechanisms of disease · middle twist