Cortisol function

Liicken, L.J. (1998) Childhood attachment and loss experiences affect adult cardiovascular and cortisol function. Psychosom Med 60 765-772. 

Molecular orbital calculations on models have provided the intergroup distances which may explain how cortisol functions as an antagonist in the Inflammatory response to histamine and serotonin. The distance between the 3-0X0 and lip-hydroxyl group, e.g., approximates the internitrogen distance previously calculated for serotonin. 

A third variation of this strategy has been appHed to an enantioselective total synthesis of cortisone. From an appropriately functionalized, scalemic hydrindan that possessed an 11-oxo-group and a masked corticoid side-chain, (+)-cortisol was produced in an 11-step total synthesis (213). 

The example given above of the selection of deoxycholic acid as a SM for the synthesis of cortisol also illustrates the use of a chiral natural substance as synthetic precursor of a chiral TGT. Here the matching process involves a mapping of individual stereocenters as well as rings, functional groups, etc. The synthesis of helminthosporal (105) from (-i-)-carvone (106)21 and the synthesis of picrotoxinin (107) from (-)-carvone (108)22 amply demonstrate this approach employing terpenes as chiral SM s. 

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. 

Interference with corticosteroid function and the stress response has been shown for a variety of chemicals, including the pharmaceutical salicylate (Gravel and Vijayan 2006) and the PAH, phenanthrene (Monteiro et al. 2000a, 2000b). Other classes of chemicals shown to have significant effects on cortisol levels include PCBs and PAHs (Hontela et al. 1992,1997). The precise mechanisms for these effects are poorly understood, but for PCBs, are believed to be via their actions through the Ah receptor (Aluru and Vijayan 2006). 

Some clinicians advocate a baseline cortisol level <15 mcg/dlV or <25 mcg/dL in critically ill patients as the diagnostic threshold for relative (or functional) adrenal insufficiency... 

Adrenal insufficiency generally refers to the inability of the adrenal glands to produce adequate amounts of cortisol for normal physiologic functioning or in times of stress. The... 

M20. Melby, J. C., and Spink, W. W., Comparative studies on adrenal cortical function and cortisol metabolism in healthy adults and in patients with shock due to infection. J. Clin. Invest. 37, 1791-1798 (1958). 

Discuss functions and factors regulating release of the following hormones thyroid hormones, calcitonin, parathyroid hormone, catecholamines, aldosterone, cortisol, adrenal androgens, insulin, and glucagon... 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

Adrenal gland A triangle-shaped organ positioned at the top of the kidney which functions as a double endocrine gland . The larger outer adrenal cortex secretes three classes of steroid hormones glucocorticoids (e.g., cortisol), minerlocorticoids (aldosterone) and small amounts of sex steroids (e.g., testosterone). The inner adrenal medulla secretes catecholamines (e.g., adrenaline and noradrenaline). 

Price, L. H., Charney, D. S., Rubin, A. L. and Heninger, G. R. Alpha 2-adrenergic receptor function in depression. The cortisol response to Yohimbine. Arch. Gen. Psych. 43 849-858,1986. 

Theory Cortisol (or hydrocortisone) was introduced in the year 1951, for the treatment of rheumatoid arthritis. It has a significant effect on protein metabolism. It also exerts widespread effects on carbohydrates, lipid and protein synthesis (or anabolism). The cardinal side effects such as excessive potassium excretion and sodium retention, enhanced gastric acidity, oedema, psychosis and negative nitogen balance are some of the exaggerated manifestations of the normal metabolite functions of cortisol. 

Figure 12.11 The cortisol pyramid. On the basis of the biochemical and physiological effects, the function of the hormone is the chronic maintenance of the blood glucose and glutamine levels. FFA - long-chain fatty acids.

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