Adrenocorticotropic hormone

Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone produced and secreted by the pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with corticotropin-releasing hormone). Its principal effects are increased production of androgens and, as its name suggests, cortisol.

Production

ACTH is synthesised from pro-opiomelanocortin (POMC) and secreted from corticotropes in the anterior lobe (or adenohypophysis) of the pituitary gland in response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus. It is also produced by cells of immune system (T cells, B cells and macrophages) as a response to stimuli that go along with stress (including CRH).

POMC is cleaved into ACTH and β-lipotropin. γ-lipotropin and β-endorphin result from the cleavage of this β-lipotropin.

Structure

ACTH consists of 39 amino acids, the first 13 of which (counting from the N-terminus) may be cleaved to form α-melanocyte-stimulating hormone (α-MSH). (This common structure is one reason that patients with hypocortisolism or Addison's disease, in which ACTH levels are elevated, often present with excessively tanned skin.)

After a short period of time, ACTH is cleaved into α-melanocyte-stimulating hormone (α-MSH) and CLIP, a peptide with unknown activity in humans.

Function

ACTH acts through the stimulation of cell surface ACTH receptors, which are primarily located on the adrenocortical cells. ACTH stimulates the cortex of the adrenal gland and boosts the synthesis of corticosteroids, mainly glucocorticoids but also sex steroids (androgens).

ACTH is also related to the circadian rhythm in many organisms.

The half-life of ACTH in human blood is about ten minutes.

Synthetic ACTH

An active synthetic form of ACTH, consisting of the first 23 amino acids of native ACTH, was first synthesized by Klaus Hofmann at the University of Pittsburgh. ACTH is available as a synthetic derivative in the forms of cosyntropin, tradename Cortrosyn and synacthen (synthetic ACTH). Both are very rarely used in place of glucocorticoids to treat secondary adrenal insufficiency in a hospital setting, but are primarily used to conduct the ACTH stimulation test.

ACTH was first synthesized as a replacement for Acthar Gel, a long-lasting animal product. Once relatively inexpensive, it is currently an extremely expensive pharmaceutical product. Prices per vial have been as high as $25,000.

Associated conditions

• Addison's disease
• Small cell carcinoma (a common cause of ACTH secreted ectopically)
• Adrenoleukodystrophy
• Congenital adrenal hyperplasia
• Cushing's syndrome
• Nelson's syndrome
• West syndrome, AKA Infantile Spasms

References

See also

• Pituitary-adrenal axis
• ACTH stimulation test