Corticosteroids

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Corticosteroids or corticosteroids (from the Latin cortex = 'bark'; gr. Stereos , στερεος = 'solid'), also written corticoids , corticoids or cortins , are a group of around 50 steroid hormones formed in the adrenal cortex (the cortex of the adrenal gland) as well as chemically comparable synthetic substances. All corticoids are created from the raw material cholesterol . The common basic structure of the hormones is progesterone (Δ4-pregnen-3,20-dione).

The basic structure of all corticoids is progesterone

The corticosteroids can be divided into three groups according to their biological effect or where they are formed:

Natural glucocorticoids include cortisone , corticosterone, and cortisol ; to the mineralocorticoids aldosterone and deoxycorticosterone isolated by Reichstein as early as 1935 . Synthetic corticoids are e.g. B. prednisone and prednisolone , methylprednisolone , triamcinolone , dexamethasone , betamethasone and paramethasone .

synthesis

The different hormones are formed from progesterone by hydroxylation (incorporation of OH groups) and oxidation of these groups to keto or aldehyde groups at different positions. The synthesis and secretion of androgens and glucocorticoids is stimulated by ACTH (corticotropin) from the adenohypophysis (anterior pituitary lobe of the pituitary gland ). The synthesis and secretion of the mineralocorticoids is stimulated by angiotensin II and potassium.

effect

Corticosteroids act as lipophilic hormones on receptors in the cytosol and cell nucleus, to which they can freely diffuse through the cell membrane . In the meantime, however, the existence of membrane-based receptors for corticoids is also assumed and researched. The receptors inside the cell can be divided into two types. Type I is specific for mineral corticoids and type II for glucocorticoids. The specificity of the receptors seems to depend on the activity of 11 β -hydroxysteroid dehydrogenase 1 , which occurs through dehydration of the β-OH group on the C 11 atom. This makes the corticoids (with the exception of aldosterone ) ineffective. Excessive consumption of licorice can inhibit 11-hydroxysteroid dehydrogenase and thus lead to stronger effects of the mineral corticoids.

Overproduction, shortage

Pathological overproduction, for example during stress , or long-term use of glucocorticoids produce a characteristic clinical picture ( Cushing's syndrome ) with osteoporosis , diabetes mellitus , obesity (especially trunk obesity ) and muscle wasting. Mineralocorticoid concentrations that are too high disrupt the water-electrolyte balance and damage the kidneys ( Conn syndrome ).

A lack of adrenal hormones creates Addison's disease , a life-threatening disease with poor circulation, dehydration and cachexia . A particular genetic defect in which too much androgens and too little aldosterone are produced causes virilism and water retention ; the full picture of the disease is called adrenogenital syndrome .

Dismantling

Corticoids are in the liver by reduction converted into inactive derivatives (17-hydroxy, 17-ketosteroids) and excreted in urine and bile.

therapy

Except for the above In deficiency states, glucocorticoids in particular are used as medication in numerous immune diseases and emergency situations. The natural corticoids are less effective than the artificial corticoids. Drugs with a higher affinity bind more easily to the receptors and have a greater effect at the same drug concentration.

Equivalence doses (the equally effective dose of cortisone) are given for oral and intravenous therapy. Prednisone (17 α , 21-dihydroxy-1,4-pregnadiene-3,20-dione) is an artificial corticoid, which corresponds to a dehydrated variant of cortisone. Its effect is about four to five times that of cortisone.

Corticoids are used to treat u. a. Autoimmune diseases such as asthma , cluster headache , eczema , epilepsy , sudden hearing loss as well as acute tinnitus , nephritis , neurodermatitis and with certain chemotherapies ( Hodgkin's disease , NHL ).

unwanted effects

Since corticosteroids induce overproduction of gastric acid, a proton pump inhibitor should also be taken for long-term administration in order to prevent the development of a gastric ulcer . In general, especially with long-term and / or high-dose use, a large number of side effects can occur, in particular disorders in the hypothalamus-pituitary-adrenal axis with the consequence of secondary adrenal insufficiency (e.g. Cushing's syndrome , see also paragraph Overproduction ), which require careful consideration when applying. In the case of shock therapy for the treatment of epilepsy or a multiple sclerosis flare-up, a gastric protection agent must be administered approximately one hour after taking a dose.

Due to the immunosuppressive effect of glucocorticoids, infections with viruses, bacteria or fungi often occur in patients due to the weakened immune defense.

literature

  • Jeremy M. Berg, John L. Tymoczko, Lubert Stryer : Biochemistry. 6 edition, Spektrum Akademischer Verlag, Heidelberg 2007. ISBN 978-3-8274-1800-5 .
  • Donald Voet, Judith G. Voet: Biochemistry. 3rd edition, John Wiley & Sons, New York 2004. ISBN 0-471-19350-X .
  • Bruce Alberts , Alexander Johnson, Peter Walter, Julian Lewis, Martin Raff, Keith Roberts: Molecular Biology of the Cell , 5th Edition, Taylor & Francis 2007, ISBN 978-0815341062 .

Remarks

  1. ^ A b c Hans-Christian Pape, Armin Kurtz, Stefan Silbernagl: Physiology . 7th edition. Georg Thieme Verlag, Stuttgart 2014, ISBN 978-3-13-796007-2 , p. 613 .
  2. ↑ However, effectiveness has not been reliably and conclusively proven here.
  3. ↑ MM Liu, AB Reidy, S. Saatee, CD Collard: Perioperative Steroid Management - Approaches Based on Current Evidence. In: Anesthesiology. Volume 127, 2017, pp. 166-172.
  4. ↑ Michael Brendler: Fatal syringes. Frankfurter Allgemeine Sonntagszeitung, October 23, 2017.