Cortisol activity

Like all steroids, aldosterone enters the target cell and combines with cytosolic mineralocorticoid receptor. Such receptors are not entirely specific for aldosterone and will also bind cortisol, the principal glucocorticoid hormone. The receptors are protected from cortisol activation by 11 3 hydroxysteroid dehydrogenase which... 

An extremely ill 51-year-old man with Cushing s syndrome, due to an ACTH-secreting pituitary macroadenoma, which had failed to respond to conventional surgical, medical, and radiotherapeutic approaches, responded dramatically in the short-term and long-term to high-dose mifepristone (up to 25 mg/kg/day) for 18 months. However, she developed severe hypokalemia, attributed to excessive cortisol activation of mineralocor-ticoid receptors it responded to spironolactone. 

A. Glucocorticoids, such as cortisol, activate the gene for PEPCK. 

A good night s sleep may do much more than refresh the psyche. Melatonin is a hormone that acts as an antioxidant that combats the free radicals (see Section 3.6.6) that can cause genetic damage. Cortisol is another hormone that helps regulate the immune systan. The disruption of normal sleep cycles results in less melatonin production and lower cortisol activity. Perhaps that may be one reason that shift workers have higher rates of breast cancer than women who sleep normal hours. Regular sleep may help to battle cancer. 

Sobering investigators uncovered a second significant breakthrough in microbial biotechnology of steroid production. They discovered that Corynebacterium simplex converted hydrocortisone (cortisol) (29) to prednisolone via a 1,2-dehydrogenation reaction. This A -3-ketosteroid is a highly active antiinflammatory commercial product (162). 

The discovery in 1954 that fluorination of the glucocorticoid hormone cortisol could bring about remarkable changes in the biological properties of the hormone was entirely unexpected and violated the then prevalent belief that synthetic variants could not surpass a naturally occurring hormone in its biological activity. Because of the impact that fluorination of steroids has had on subsequent developments in this area the history of the discovery of fluorocortisol will be briefly recounted. 

Synthetic steroid with strong glucocorticoid-agonistic activity. Dexamethasone is over 10 times more potent than cortisol due to a higher binding affinity for glucocorticoid receptor and a decreased clearance rate of the compound. Due to its potency, dexamethasone is widely used in the clinics for the treatment of inflammatory diseases. 

Although MR also binds glucocorticoids, its main ligand in classical mineralocorticoid target tissues such as kidney and colon is aldosterone ( d 1.3 nM). This can be granted to the ability of 11 (3-hydioxysteroid dehydrogenase type II (11 (3-HSD II) to convert active cortisol into its inactive metabolite cortisone in these tissues. Since aldosterone is no substrate for this enzyme it can readily bind to MR, leading to exclusive occupation of the receptor by aldosterone. In contrast, no such mechanism exists in brain and presumably... 

The main mineralocorticoid agonist in humans is aldosterone. Additionally, cortisol, corticosterone, and DOC have also mineralocorticoid agonistic activity. The synthetic steroid fludrocortisone (9a-fluorocorti-sol) is extremely potent and usually chosen for replacement mineralocorticoid therapy. In contrast, aldosterone and DOC are not useful in oral therapy due to rapid degradation in liver after absorption. 

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

Instead of activating transcription the cortisol-induced GR represses IL-6 synthesis and, even more surprisingly, repression does not involve the GRE elements, but rather the kB site (Fig. 1). It appeals that of a monomeric GR protein without itself touching the DNA interacts with the RelA component of NF-kB [3]. As a result GR blocks the action of NF-kB. The negative interference by this crosstalk is not restricted to NF-kB, it occurs also with AP-1 and CREB, and with several other transcription factors not relevant for IL-6 expression. A nuclear isoform of the LIM protein Trip6 mediates the interaction between these factors and is required for the inhibitory GR function. This interesting negative crosstalk is part of the immune-suppressive action of cortisol. 

Table VI lists several drugs Inducing hepatic microsomal enzymes (5). These enzymes can metabolize the drug as well as other substrates. Barbiturates, grlseofulvln, and glutethlmlde Induce enzymes which metabolize coumarln and phenlndlone derivatives and thus reduce their anticoagulant activity. Dlphenylhydantoln and phenylbutazone stimulate cortisol hydroxylase activity and Increase the urinary excretion of B-hydroxy cortisol and decrease the concentration of cortisol In the plasma.

Mooradian (1993) has studied the antioxidant properties of 14 steroids in a non-membranous system in which the fluorescence of the protein phycoerythrin was measured in the presence of a lipid peroxyl radical generator (ABAP). Oxidation of the protein produces a fluorescent species. Quenching of fluorescence by a test compound indicates antioxidant activity. Oestrone, testosterone, progesterone, androstenedione, dehydroepian-drosterone, cortisol, tetrahydrocortisone, deoxycorti-... 

IL-6 (21-28) Monocyte/macrophage, T cell endothelium, fibroblast, keratinocyte Induction of fever and the hepatic acute phase response. Stimulates cortisol production. Decreases IL-1 and TNF production. Participates in activation of B and T cells, facilitates Ig production by B cells. Induction of granulocyte-macrophage colony-stimulating factor, stimulation of hematopoietic progenitors. 

R17. Ross, R. J Miell, J. P Holly, J. M. P., Maheshwari, H., Norman, M., Farhana Abdulla, A., and Buchanant, C. R., Levels of GH binding activity, IGFBP-I, insulin, blood glucose, and cortisol in intensive care patients. Clin. Endocrinol. 35,361-367 (1991). 

A trophic hormone acts on another endocrine gland to stimulate secretion of its hormone. For example, thyrotropin, or thyroid-stimulating hormone (TSH), stimulates the secretion of thyroid hormones. Adrenocorticotropin, or adrenocorticotropic hormone (ACTH), stimulates the adrenal cortex to secrete the hormone cortisol. Both trophic hormones are produced by the pituitary gland in fact, many trophic hormones are secreted by the pituitary. The pituitary gland is sometimes referred to as the "master gland" because its hormones regulate the activity of other endocrine glands. 

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