Cortisol derivatives

Varelis P, Smythe GA, Hodgson D, Lazarus L. Measurement of urinary free cortisol by stable isotope dilution mass spectrometry using a new cortisol derivative. J Chromatogr B Biomed Appl 1994 660 151-9. 

The adrenal cortex secretes aldosterone, cortisol and testosterone from different layers. Aldosterone causes salt and water reabsorption in the kidney if blood pressure or blood volume is low. Cortisol has a complex role in the body, being able to increase circulating glucose levels and mobilize amino acids and fatty acids in response to stress and trauma. Cortisol derived drugs are used therapeutically for their anti-inflammatory and immunosuppressant actions. 

Comparative MTV and free-Wilson Study of Anti-In lamatory Activity 0 Substituted Cortisol derivatives... 

Geometrical isomeric mixtures of steroidal oxime esters have been evaluated for the enzymatic transformations. In this respect, the work by Adamczyk and co-workers [27] describes the use of lipase from CCL in the diastereoselective hydrolysis of 3-(0-carbox-ymethyl)oxime methyl esters, 17a-hydroxyprogesterone 122, progesterone 124, testosterone 126, and cortisol 128. CCL proved to be effective in carrying out hydrolysis of methyl esters of steroidal 3-carboxymethyl oximes in a mild manner affording the E and Z dia-stereoisomers 123/122, 125/124, 127/126, and 129/128 in different ratios. The enzyme exhibited a preference for the anti isomer (Table 11). The faster rate and greater selectivity observed for 128 is probably due to the cortisol derivative s better solubility in the reaction media. 

The outer layer or cortex of the adrenal gland is the source of a large group of sub stances known as corticosteroids Like the bile acids they are derived from cholesterol by oxidation with cleavage of a portion of the alkyl substituent on the D ring Cortisol IS the most abundant of the corticosteroids but cortisone is probably the best known Cortisone is commonly prescribed as an antiinflammatory drug especially m the treat ment of rheumatoid arthritis... 

FIGURE 25.43 The steroid hormones are synthesized from cholesterol, with intermediate formation of pregnenolone and progesterone. Testosterone, the principal male sex hormone steroid, is a precursor to /3-estradiol. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are also derived from progesterone. 

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. 

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.

A. 17,20 lyase is required for androgen synthesis, cyclooxygenase for prostaglandin production, 11- 3-hydroxysteroid dehydrogenase-2 acts as a reductase-converting cortisol to its inactive 11-keto derivative cortisone, whereas 18-hydroxylase is required for aldosterone production. 

Ultra-sensitive differential measurement of cortisol and > cortisone in biological samples using fluorescent ester derivatives in normal phase HPLC. (162)... 

---