ACTH is Released from the Anterior Pituitary Gland
ACTH (adrenocorticotropic hormone) is released from the anterior pituitary gland, not from within the brain itself, though the pituitary is anatomically located at the base of the brain. The pituitary gland sits in the sella turcica and is controlled by the hypothalamus above it 1, 2.
The Hypothalamic-Pituitary-Adrenal (HPA) Axis
The release mechanism works as follows:
- Corticotropin-releasing hormone (CRH) is produced in the hypothalamus (specifically the paraventricular nucleus)
- CRH travels down to stimulate the anterior pituitary gland
- The anterior pituitary then releases ACTH into the bloodstream 1, 3
- ACTH subsequently acts on the adrenal cortex to stimulate cortisol production 2
Important Clinical Context
Central vs. Peripheral Distinction
When diagnosing conditions like Cushing's disease, clinicians distinguish between:
- Central (pituitary) sources of ACTH excess - from the anterior pituitary 4
- Ectopic sources - from tumors outside the pituitary (lung, thyroid, pancreas, bowel) 5, 6
This is why bilateral inferior petrosal sinus sampling (BSIPSS) measures the central-to-peripheral ACTH gradient - comparing ACTH levels from pituitary venous drainage versus peripheral blood to confirm pituitary origin 4.
ACTH-Containing Neurons in Brain
While ACTH is released from the anterior pituitary, research has identified ACTH-immunoreactive neurons in other brain regions including the arcuate nucleus of the hypothalamus, dorsal hypothalamus, and amygdala 7, 8, 9. However, these appear to serve neuromodulatory functions rather than being the primary source of circulating ACTH that regulates adrenal function.
The clinically relevant answer: ACTH that regulates cortisol production is released from the anterior pituitary gland 2, 1, 2.