Dr. med. Dirk Manski



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Adrenal Glands: Corticosteroids

References: (Benninghoff, 1993).

Biochemistry of steroid hormone production

All Corticosteroids are synthesized from a common precursor hormone (pregnenolone), which is produced from cholesterol by the P450SCC (cholesterol side chain cleavage). Corticosteroids include mineralocorticoids, glucocorticoids and androgens [fig synthesis of corticosteroids].


fig. steroid biosynthesis: corticosteroids are synthesized from a common precursor hormone (pregnenolone), which is produced from cholesterol by the P450SCC (cholesterol side chain cleavage). Corticosteroids include mineralocorticoids, glucocorticoids and androgens. DHEA = dehydroepiandrosterone, 17OH-Preg. = 17-hydroxy-pregnenolone, 17OH-Prog. = 17-hydroxy-progesterone, 17β-HSO = 17β-hydroxysteroid oxidoreductase, 3β-HSD = 3β-hydroxysteroid dehydrogenase.
fig. steroid biosynthesis: corticosteroids are synthesized from a common precursor hormone (pregnenolone), which is produced from cholesterol by the P450SCC (cholesterol side chain cleavage).  Corticosteroids include mineralocorticoids, glucocorticoids and androgens. DHEA = dehydroepiandrosterone, 17OH-Preg. = 17-hydroxy-pregnenolone, 17OH-Prog. = 17-hydroxy-progesterone, 17β-HSO = 17β-hydroxysteroid oxidoreductase, 3β-HSD = 3β-hydroxysteroid dehydrogenase.

The adrenals produce dehydroepiandrosterone and androstenedione from 17-hydroxy-pregnenolone and 17-hydroxy progesterone. The genital organs convert the androgens into testosterone, dihydrotestosterone, estriol and estradiol. Androgens from the adrenals become clinical significant in the following circumstances: enzyme defects of steroid synthesis (adrenogenital syndrome) or in metastatic prostate cancer.

Regulation of Glucocorticoids

Corticotropin-releasing hormone (CRH):

CRH is a hypothalamic hormone of 41 amino acids, which is transported via the bloodstream to the anterior pituitary, where it stimulates the release of ACTH (adrenocorticotropic hormone).

Adrenocorticotropic hormone (ACTH):

ACTH is a protein hormone produced by the cleavage of pro-opiomelanocortin (POMC). The cleavage also forms β-lipotropin (β- LPH), β-melanocyte-stimulating hormone (β-MSH), β-endorphin and met-enkephalin.

ACTH leads to the release of cortisone; cortisone conversely prevents the release of ACTH (negative feedback). ACTH leads, to a lesser extent, also to the release of androgens. The following substances stimulate (in addition to CRH) the release of ACTH: vasopressin, oxytocin, adrenaline, angiotensin II, vasoactive intestinal peptide (VIP), serotonin, gastrin-releasing peptide, atrial natriuretic factor (ANF) and γ-aminobutyric acid (GABA).

Molecular mechanisms of cortisone action:

Glucocorticoids passively diffuse into the cell and bind to the nuclear steroid receptor proteins. The activated steroid receptors bind to specific DNA sequences (steroid response elements, SRE) and lead to increased gene expression.

Addition to the nuclear mechanism, glucocorticoids have direct influence on the ACTH release, prostaglandin synthesis, preventing calcium influx into the cell, inhibition of protein kinase C and binding to membrane receptors.

Effects of Glucocorticoids

Metabolism and glucocorticoids:

increased gluconeogenesis and lipolysis, increase of blood sugar and blood fats, redistribution of fat storage.

Electrolytes and glucocorticoids:

glucocorticoids possess also mineralocorticoid effects: retention of sodium, loss of potassium, increase in extracellular fluid and blood pressure, calcium excretion (vitamin D antagonist).

Musculoskeletal system and glucocorticoids:

osteoblast inhibition, osteoporosis, Vit-D antagonist, hypocalcaemia, catabolic, myopathy, muscle atrophy.

Blood system and glucocorticoids:

lymphocytopenia, increased neutrophils, polycythemia, thrombocytosis, increased risk of thrombosis.

Immune system and glucocorticoids:

lymphopenia, inhibition of chemotactic factors (IL1, IL2, macrophages, MIF, ...). This leads to reduced humoral and cellular immune response. Glucocorticoids also inhibit the early inflammatory response (oedema, fibrin, capillary dilation and permeability, migration) and the late inflammatory response (capillary and fibroblast proliferation).

Skin and glucocorticoids:

atrophy, fragile vessels, telangiectasia, stretch marks.

CNS and glucocorticoids:

euphoric, dysphoric reaction, however, also possible. Increased excitability. Steroid cataract.

Aldosterone

The most important stimulus for the secretion of aldosterone is the renin-angiotensin-aldosterone system (RAAS), see chapter anatomy and physiology of the kidney.








Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z



References

Benninghoff 1993 BENNINGHOFF, A.:
Makroskopische Anatomie, Embryologie und Histologie des Menschen.
15. Auflage.
München; Wien; Baltimore : Urban und Schwarzenberg, 1993


  Deutsche Version: Corticosteroide der Nebennieren.