CRH

Where it comes from

Made in

The paraventricular nucleus of the hypothalamus; amygdala, cortex, gut; and the placenta, in huge amounts

Sent out by

Stress of any kind, the morning rhythm, and inflammatory cytokines; cortisol feeds back on it

Acts on

• Pituitary corticotrophs
• Locus coeruleus and amygdala (arousal, fear)
• Gut (motility)
• Immune cells

What it does

• Releases ACTH and so cortisol
• Drives the arousal, anxiety and loss of appetite of stress
• Placental CRH rises through pregnancy and helps time labour, the “placental clock”

In medicine

• The CRH stimulation test (with petrosal sinus sampling) tells pituitary from ectopic Cushing’s; the ovine CRH product has been discontinued in the United States, and human CRH is used where available
• Crinecerfont (2024), a CRHR1 blocker, treats congenital adrenal hyperplasia by lowering ACTH, so less steroid is needed ⁴

Beyond the body’s own use

• In 182 adults with congenital adrenal hyperplasia, crinecerfont let the daily glucocorticoid dose fall by 27 per cent against 10 per cent on placebo while androgen control held, and 63 per cent reached a physiological dose ¹
• As an antidepressant the same idea failed: a six-week randomised trial of a selective CRH1 antagonist in major depression showed no separation from placebo ²
• It failed again in generalised anxiety disorder, where a CRF1 antagonist did no better than placebo although the active comparator worked ³
• CRH is still studied in irritable bowel syndrome, where it links stress to gut cramping, and nothing aimed at that has reached approval