Adrenocorticotropin

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Proopiomelanocortin derivatives
POMC
     
γ-MSH ACTH β-lipotropin
         
  α-MSH CLIP γ-lipotropin β-endorphin
       
    β-MSH  

Adrenocorticotropin , including adrenocorticotropic hormone (short ACTH ) is a normally from the pituitary emitted hormone that among other things the corticoid - release by the adrenal controls. It is a peptide hormone that is formed under the influence of the corticotropin-releasing hormone (CRH) in the basophilic cells of the anterior pituitary gland from the precursor of proopiomelanocortin (POMC). It regulates the synthesis of important enzymes for steroid synthesis . Among other things, the synthesis of pregnenolone is stimulated, the limiting step in steroid synthesis.

synthesis

Adrenocorticotropin is produced under the influence of the corticotropin-releasing hormone (CRH) in the basophilic cells of the anterior pituitary gland . Due to the limited proteolysis , the proopiomelanocortin not only produces ACTH, but also lipotropin or, instead of ACTH and lipotropin, melanocyte-stimulating hormone (MSH) and an endorphin can develop.

ACTH formation can also occur (ectopic) in malignant tumors of the adrenal cortex, for example in paraneoplastic Cushing's syndrome.

effect

ACTH has a particular effect on the adrenal cortex, where it primarily stimulates the cells of the zona fasciculata to form glucocorticoids . The formation of mineralocorticoids and sex hormones is also stimulated.

The main biochemical effects develop ACTH as an agonist of the melanocortin receptors , in particular the G-protein-coupled melanocortin receptor 2 . The cAMP synthesis from ATP and thus protein kinase A is stimulated via this receptor . Protein kinase A mainly activates three enzymes through phosphorylation:

  • StAR (Steroidogenic Acute Regulatory Proteins), which carries out the absorption of cholesterol into the mitochondria and represents the decisive step in steroid biosynthesis,
  • the cholesterol hydrolase , which provides free cholesterol and
  • CREB (cAMP response element-binding protein), a transcription factor for the expression of StAR and other steroidogenic enzymes.

When crying (for emotional reasons, not eye irritation), tears contain adrenocorticotropin.

Stress hormone

Since ACTH is increasingly released in various forms of stress, it is also known as the stress hormone . Possible stressors are work, injuries, illnesses, operations, emotions, depression, physical and psychological stress.

Regulation of ACTH secretion

The secretion of ACTH is regulated by the hypothalamus by means of feedback inhibition. The release of ACTH is subject to a circadian rhythm , so that the concentration, like that of the glucocorticoids, is highest in the early morning and lowest in the late evening. Physical and psychological stress also stimulates ACTH secretion, which is why phasic secretory episodes of the ultradian rhythm occur at regular intervals in addition to the normal circadian rhythm .

use

Use in diagnostics

In diagnostics, adrenocorticotropin is used in the ACTH stimulation test , especially for the diagnosis of adrenal insufficiency or adrenogenital syndrome .

Use in therapy

epilepsy

ACTH is often used in the therapy of epileptic seizures, especially in West syndrome . After short to medium-term therapy, up to eight out of ten children with West Syndrome become seizure-free. Premature babies are an exception: they apparently respond much less frequently to ACTH; presumably due to the level of development of the brain or the perivascular white matter.

An ACTH cure is fraught with high risks due to sometimes massive side effects , which depend on the respective duration and the dose. I.a. there may be leukocytosis , weakening of the immune system , hyperglycemia , hypertension , vomiting , stomach bleeding , heart failure and Cushing's syndrome come.

The relapse rate after ACTH therapy is up to about 65% in West syndrome.

Others

ACTH has also been used in the treatment of gout .

Excess and deficiency

Elevated ACTH values ​​result from cold, stress, adrenal insufficiency , Cushing's disease or paraneoplastic syndrome. Reduced ACTH levels occur in Sheehan's syndrome , changes in the pituitary gland , the hypothalamus or the pituitary stalk. Possible changes in the pituitary gland result from tumors of the pituitary gland or the brain, operations, radiation, bleeding, infarcts, infections, inflammations, granulomas or metastases in the area of ​​the pituitary gland. Possible changes in the hypothalamus, which regulates ACTH production in the pituitary gland with CRH, include tumors, surgery, or radiation. If the pituitary stalk is injured, the ACTH values ​​decrease because the hypothalamus, together with the CRH, can no longer drive the production of ACTH in the anterior pituitary gland .

A lack of ACTH causes atrophy of the adrenal cortex.

Derivatives

Pro-Gly-Pro-ACTH (4-7) is used in Russia as a nootropic , including after a stroke .

Individual evidence

  1. ↑ a b Eckert R., ea: Tierphysiologie , Georg Thieme Verlag, 2002, p. 335, ISBN 3136640047 , here online
  2. ^ A b Hans-Christian Pape, Armin Kurtz, Stefan Silbernagl: Physiology . 7th edition. Georg Thieme Verlag, Stuttgart 2014, ISBN 978-3-13-796007-2 , p. 611 .
  3. ↑ D. Klaus: Diseases of the adrenal cortex. In: Rudolf Gross , Paul Schölmerich , Wolfgang Gerok (Eds.): 1000 memoranda of internal medicine. Schattauer, Stuttgart / New York 1971; 4th, completely revised edition ibid 1989 (= UTB für Wissenschaft / Uni-Taschenbücher. Volume 522), ISBN 3-7945-1282-0 , pp. 170–174, here: p. 171.
  4. ^ G. Löffler, PE Petrides, PC Heinrich: Biochemie & Pathobiochemie. 9th edition, Springer, Heidelberg 2014, ISBN 978-3-642-17971-6 , pp. 495-497.
  5. ↑ Amplitude, but not frequency, modulation of adrenocorticotropin secretory bursts gives rise to the nyctohemeral rhythm of the corticotropic axis in man. ( Memento from June 9, 2010 in the Internet Archive )
  6. ↑ Internal medicine . Georg Thieme, Stuttgart 2001, ISBN 978-3-13-128751-9 , pp. 866 .
  7. ↑ William Charles Kuzell, Guy-Pierre Gaudin: gout. (= Documenta Rheumatologica. Volume 10). JR Geigy, Basel 1956, p. 11.
This text is based in whole or in part on the ACTH entry in Flexikon , a wiki from DocCheck . The takeover took place on January 12, 2007 under the then valid GNU license for free documentation .