Adrenocorticotropin (ACTH) – Hormone & Function
Adrenocorticotropin (ACTH) is a pituitary hormone that stimulates the adrenal cortex to produce cortisol and plays a key role in the body´s stress response system.
Things worth knowing about "Adrenocorticotropin"
Adrenocorticotropin (ACTH) is a pituitary hormone that stimulates the adrenal cortex to produce cortisol and plays a key role in the body´s stress response system.
What is Adrenocorticotropin?
Adrenocorticotropin (commonly abbreviated as ACTH, also known as corticotropin) is a peptide hormone produced and secreted by the anterior pituitary gland. It is a crucial component of the hypothalamic-pituitary-adrenal (HPA) axis, which governs the body´s response to stress and regulates numerous physiological processes.
Mechanism of Action
ACTH is derived from a precursor protein called proopiomelanocortin (POMC). Its release from the pituitary is triggered by corticotropin-releasing hormone (CRH) from the hypothalamus. Once in the bloodstream, ACTH travels to the adrenal cortex, where it binds to specific receptors (MC2 receptors) and stimulates the synthesis and release of cortisol, as well as smaller amounts of other glucocorticoids and adrenal androgens.
The system is regulated by a negative feedback loop: elevated cortisol levels suppress both CRH secretion from the hypothalamus and ACTH release from the pituitary.
Biological Functions
- Stimulation of cortisol production in the adrenal cortex
- Activation and regulation of the stress response
- Modulation of metabolism, immune function, and inflammation
- Influence on blood pressure and electrolyte balance
- Trophic (growth-supporting) effect on adrenal cortex tissue
Circadian Rhythm of ACTH
ACTH secretion follows a distinct circadian (daily) rhythm, with peak levels occurring in the early morning hours and declining throughout the day. Stress, sleep deprivation, hypoglycemia, and other physiological challenges can further stimulate ACTH release.
Clinical Significance
Excess ACTH
Abnormally elevated ACTH levels lead to excessive cortisol production. This can result from:
- Cushing disease: An ACTH-secreting tumor of the pituitary gland
- Ectopic ACTH syndrome: ACTH production by non-pituitary tumors (e.g., small cell lung carcinoma)
ACTH Deficiency
Insufficient ACTH leads to reduced cortisol production, known as secondary adrenal insufficiency. Common causes include:
- Pituitary tumors or damage
- Long-term corticosteroid therapy (suppression of the HPA axis)
- Sheehan syndrome (pituitary infarction following childbirth)
Diagnostic Applications
The ACTH stimulation test (also known as the Synacthen test) is widely used to assess adrenal cortex function. Synthetic ACTH (tetracosactide) is administered, and the cortisol response is measured. This test is essential in diagnosing adrenal insufficiency (Addison disease) and other HPA axis disorders.
Baseline ACTH levels are typically measured in the morning (between 7 and 9 a.m.) to account for circadian variation. Blood samples must be handled carefully -- collected in chilled tubes and processed promptly to ensure accurate results.
Therapeutic Applications
Synthetic ACTH analogues are used clinically in several contexts:
- Tetracosactide (Synacthen): Used both diagnostically and therapeutically in certain inflammatory conditions
- Management of specific pediatric epilepsy syndromes, such as West syndrome (infantile spasms)
References
- Chrousos G.P. - Stress and disorders of the stress system. Nature Reviews Endocrinology, 5(7), 374-381 (2009). PubMed PMID: 19488073
- Melmed S. et al. - Williams Textbook of Endocrinology, 14th Edition, Elsevier (2020)
- World Health Organization (WHO) - Endocrine Disorders: Adrenal Gland Pathologies. WHO Technical Report Series (updated guidelines)
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