Where ACTH is Produced
Adrenocorticotropic hormone (ACTH) is produced by cells in the anterior pituitary gland, specifically by corticotroph cells that synthesize ACTH from the precursor molecule proopiomelanocortin (POMC). 1, 2
Anatomical Location and Cellular Origin
ACTH is secreted by the anterior pituitary system under the influence of hypothalamic trophic factors, specifically corticotropin-releasing hormone (CRH) from the hypothalamus. 1
The anterior pituitary gland contains specialized corticotroph cells that are responsible for ACTH production and release. 1
ACTH production occurs through the processing of a larger precursor molecule called proopiomelanocortin (POMC), which is cleaved to produce both ACTH and beta-endorphin, typically within the same cells. 3, 2
Molecular Forms and Processing
ACTH exists in multiple molecular weight forms within the pituitary gland, including "big" ACTH (molecular weight ~44,000), "intermediate" ACTH (molecular weight ~13,000), and "little" ACTH (molecular weight ~4,500). 4, 5
The smaller molecular weight forms demonstrate higher biological activity in stimulating adrenal corticosterone secretion compared to the larger "big" ACTH form. 4
Both the anterior lobe and the neurointermediate lobe of the pituitary contain ACTH, though the anterior lobe contains approximately ten times more ACTH activity than the intermediate-posterior lobe. 5
Regulatory Control
ACTH release follows a circadian rhythm with highest levels in the morning (reference range 140-700 nmol/L at 0900) and lowest levels at midnight (80-350 nmol/L). 1
The hypothalamic-pituitary-adrenal axis operates through a feedback loop where CRH from the hypothalamus stimulates ACTH release from the anterior pituitary, which in turn stimulates cortisol production from the adrenal cortex. 1
Under normal physiological conditions, approximately 20 mg of cortisol is released daily, but this can increase five-fold (to about 100 mg per day) following major surgery or stress. 1