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Adrenocorticotropic hormone

Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland.[1] It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of cortisol and androgens by the zona fasiculata and zona reticularis, respectively. ACTH is also related to the circadian rhythm in many organisms.[2]

This article is about adrenocorticotropic hormone as a natural hormone. For adrenocorticotropic hormone as a medication and diagnostic agent, see Adrenocorticotropic hormone (medication).

Deficiency of ACTH is an indicator of secondary adrenal insufficiency (suppressed production of ACTH due to an impairment of the pituitary gland or hypothalamus, cf. hypopituitarism) or tertiary adrenal insufficiency (disease of the hypothalamus, with a decrease in the release of corticotropin releasing hormone (CRH)). Conversely, chronically elevated ACTH levels occur in primary adrenal insufficiency (e.g. Addison's disease) when adrenal gland production of cortisol is chronically deficient. In Cushing's disease a pituitary tumor is the cause of elevated ACTH (from the anterior pituitary) and an excess of cortisol (hypercortisolism) – this constellation of signs and symptoms is known as Cushing's syndrome.

Structure[edit]

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 responsible for excessively tanned skin in Addison's disease). 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.


In human body, total weight ACTH is 4,540 atomic mass units (Da).[8]

ACTH receptors outside the adrenal gland[edit]

As indicated above, ACTH is a cleavage product of the pro-hormone, proopiomelanocortin (POMC), which also produces other hormones including α-MSH that stimulates the production of melanin. A family of related receptors mediates the actions of these hormones, the MCR, or melanocortin receptor family. These are mainly not associated with the pituitary-adrenal axis. MC2R is the ACTH receptor.[12]


While it has a crucial function in regulating the adrenal glands, it is also expressed elsewhere in the body, specifically in the osteoblast, which is responsible for making new bone, a continual and highly regulated process in the bodies of air-breathing vertebrates.[13] The functional expression of MC2R on the osteoblast was discovered by Isales et alia in 2005.[14] Since that time, it has been demonstrated that the response of bone forming cells to ACTH includes production of VEGF, as it does in the adrenal. This response might be important in maintaining osteoblast survival under some conditions.[15] If this is physiologically important, it probably functions in conditions with short-period or intermittent ACTH signaling, since with continual exposure of osteoblasts to ACTH, the effect was lost in a few hours.

History[edit]

While working on her dissertation, Evelyn M. Anderson co-discovered ACTH with James Bertram Collip and David Landsborough Thomson and, in a paper published in 1933, explained its function in the body.[16][17]


An active synthetic form of ACTH, consisting of the first 23 amino acids of native ACTH, was first made by Klaus Hofmann at the University of Pittsburgh.[18]

the gland that produces, among others, the hormone ACTH

Diseases of the pituitary

the hyposecretion of ACTH in the pituitary, leading to secondary adrenal insufficiency (a form of hypocorticism)

Hypopituitarism

the primary adrenal insufficiency (another form of hypocorticism)

Addison's disease

hypercorticism, one of the causes is hypersecretion of ACTH

Cushing's syndrome

a common cause of ACTH secreted ectopically

Small cell carcinoma

diseases in the production of cortisol

Congenital adrenal hyperplasia

the rapid enlargement of the ACTH producing pituitary after the removal of both adrenal glands

Nelson's syndrome

can be accompanied by adrenal insufficiency

Adrenoleukodystrophy

("infantile spasms"), a disease where ACTH is used as a therapy

West syndrome

(POIS), through production of tyrosine hydroxylase and dopamine β-hydroxylase, which two enzymes comprise the biochemical mechanism by which norepinephrine and epinephrine are produced.

Postorgasmic illness syndrome

Critical illness-related corticosteroid insufficiency

a genetic disorder that is characterized by adrenocorticotropic hormone deficiency combined with common variable immunodeficiency and hypogammaglobulinemia.

DAVID syndrome

a synthetic analogue fragment of adrenocorticotropic hormone

Semax

at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Adrenocorticotropic+Hormone