Adrenocorticotropic hormone

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Symbol POMC
Entrez 5443
HUGO 9201
OMIM 176830
RefSeq NM_000939
UniProt P01189
Other data
Locus Chr. 2 p23

Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It 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 corticosteroids. Primary adrenal insufficiency, also called Addison's disease, occurs when adrenal gland production of cortisol is chronically deficient, resulting in chronically elevated ACTH levels; when a pituitary tumor is the cause of elevated ACTH (from the anterior pituitary) this is known as Cushing's Disease and the constellation of signs and symptoms of the excess cortisol (hypercortisolism) is known as Cushing's syndrome. A deficiency of ACTH is a cause of secondary adrenal insufficiency. ACTH is also related to the circadian rhythm in many organisms.[1]

Production and regulation[edit]


polypeptide fragment alias abbreviation amino acid residues
NPP 27–102
melanotropin gamma γ-MSH 77–87
potential peptide 105–134
corticotropin adrenocorticotropic hormone ACTH 138–176
melanotropin alpha melanocyte-stimulating hormone α-MSH 138–150
corticotropin-like intermediate peptide CLIP 156–176
lipotropin beta β-LPH 179–267
lipotropin gamma γ-LPH 179–234
melanotropin beta β-MSH 217–234
beta-endorphin 237–267
met-enkephalin 237–241


The half-life of ACTH in human blood is about ten minutes.[4]



Human ACTH has a molecular weight of 4,540 atomic mass units (Da).[5]


ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal cortex cells, especially in the zona fasciculata of the adrenal glands. ACTH acts by binding to cell surface ACTH receptors, which are located primarily on adrenocortical cells of the adrenal cortex. The ACTH receptor is a seven-membrane-spanning G protein-coupled receptor.[6] Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP[7] and subsequent activation of protein kinase A.


The long term actions of ACTH include stimulation of the transcription of the genes coding for steroidogenic enzymes, especially P450scc, steroid 11β-hydroxylase, and their associated electron transfer proteins.[7] This effect is observed over several hours.[7]

In addition to steroidogenic enzymes, ACTH also enhances transcription of mitochondrial genes that encode for subunits of mitochondrial oxidative phosphorylation systems.[8] These actions are probably necessary to supply the enhanced energy needs of adrenocortical cells stimulated by ACTH.[8]


ACTH receptors outside of the adrenal gland[edit]


Synthetic ACTH[edit]

An active synthetic form of ACTH, consisting of the first 24 amino acids of native ACTH, was first synthesized by Klaus Hofmann at the University of Pittsburgh.[12] ACTH is available as a synthetic derivative in the forms of cosyntropin, tradename Cortrosyn, and Synacthen (synthetic ACTH). Synacthen is not FDA approved but is used in the UK and Australia to conduct the ACTH stimulation test.

ACTH was first synthesized as a replacement for Acthar Gel, a long-lasting animal product used to treat infantile spasms. Once relatively inexpensive, Acthar Gel is currently an extremely expensive pharmaceutical product. Prices per vial have been as high as $36,000.[13][14] Acthar gel has been proposed as a therapy to treat refractory autoimmune diseases[13] and refractory nephrotic syndrome due to a variety of glomerular diseases.[15]

Associated conditions[edit]

See also[edit]


  1. ^ Dibner, Charna; Schibler, Ueli; Albrecht, Urs (2010). "The Mammalian Circadian Timing System: Organization and Coordination of Central and Peripheral Clocks". Annual Review of Physiology 72: 517–549. doi:10.1146/annurev-physiol-021909-135821. PMID 20148687 
  2. ^ "Adrenocorticotropic Hormone (ACTH)". 
  3. ^ "Pro-opiomelocortin precursor". Retrieved 8 April 2013. 
  4. ^ Yalow RS, Glick SM, Roth J, Berson SA (November 1964). "Radioimmunoassay of human plasma ACTH". J. Clin. Endocrinol. Metab. 24 (11): 1219–25. doi:10.1210/jcem-24-11-1219. PMID 14230021. 
  5. ^ PROOPIOMELANOCORTIN; NCBI --> POMC Retrieved on September 28, 2009
  6. ^ Raikhinstein M, Zohar M, Hanukoglu I (February 1994). "cDNA cloning and sequence analysis of the bovine adrenocorticotropic hormone (ACTH) receptor". Biochim. Biophys. Acta 1220 (3): 329–32. doi:10.1016/0167-4889(94)90157-0. PMID 8305507. 
  7. ^ a b c Hanukoglu I, Feuchtwanger R, Hanukoglu A (November 1990). "Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells". J. Biol. Chem. 265 (33): 20602–8. PMID 2173715. 
  8. ^ a b Raikhinstein M, Hanukoglu I; Hanukoglu, I. (November 1993). "Mitochondrial-genome-encoded RNAs: differential regulation by corticotropin in bovine adrenocortical cells". Proc. Natl. Acad. Sci. U.S.A. 90 (22): 10509–13. Bibcode:1993PNAS...9010509R. doi:10.1073/pnas.90.22.10509. PMC 47806. PMID 7504267. 
  9. ^ Isales CM, Zaidi M, Blair HC (March 2010). "ACTH is a novel regulator of bone mass". Ann. N. Y. Acad. Sci. 1192: 110–6. doi:10.1111/j.1749-6632.2009.05231.x. PMID 20392225. 
  12. ^ "Simulated ACTH". Time. December 12, 1960. 
  13. ^ a b Gettig J, Cummings JP, Matuszewski K (May 2009). "H.P. Acthar gel and cosyntropin review: clinical and financial implications". P T 34 (5): 250–7. PMC 2697107. PMID 19561871. 
  15. ^ Bomback AS, Tumlin JA, Baranski J, Bourdeau JE, Besarab A, Appel AS, Radhakrishnan J, Appel GB (2011). "Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel". Drug Des Devel Ther 5: 147–53. doi:10.2147/DDDT.S17521. PMC 3063118. PMID 21448451. 

External links[edit]