Metabolism cortisol

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). 

Primary adrenal insufficiency (Addison s disease) most often involves the destruction of all regions of the adrenal cortex. There are deficiencies of cortisol, aldosterone, and the various androgens. Medications that inhibit cortisol synthesis (e.g., ketoconazole) or accelerate cortisol metabolism (e.g., phenytoin, rifampin, phenobarbital) can also cause primary adrenal insufficiency. 

S.M. Abel, D.J. Back, J.L. Maggs, B.K. Park, Cortisol metabolism by human liver in vitro. IV. Metabolism of 9ot-fluorocortisol by human liver microsomes and cytosol, J. Steroid Biochem. Mol. Biol. 46 (1993) 833-839. 

Rask, E., Walker, B. R, Soderberg, S., Livingstone, D. E. W., Eliasson, M., Johnson, O., Andrew, R, Olsson, T. (2002) Tissue-specific changes in peripheral cortisol metabolism in obese women increased adipose llfi-hydroxysteroid dehydrogenase type 1 activity. / Clin Endocrinol Metab 87, 3330-3336. 

The synthesis of adrenal steroids and major excreted metabolites is illustrated in Fig. 5.3.1. Little secreted steroid product is excreted unchanged and most of the catabolism takes place in the liver, although cortisol metabolism by the kidney is clinically important and microbial metabolism in the gut can be quantitatively significant. The major metabolic transformations of hormonal steroids and precursors are detailed by Makin [54] and summarized in Fig. 5.3.2. GC-MS steroid profiling is the technique of choice for measurement of important urinary constituents. 

This disorder must be suspected if THAldo is low (< 5 pg/24 h) without manifestations of disordered cortisol metabolism, such as AME syndrome. A useful ratio is THAldo(xl00) Fs, which is typically <2. 

Lavery GG, Walker EA, Slabbed A, Ride JP, Shackleton CHL, Tomlinson JW, Arlt W, Stewart PM (2008) Monogenic forms of hyperandrogenism due to defects in cortisol metabolism. New Engl J Med (in press)... 

Compounds having the 16,17 ketal, eg, budesonide, amcinonide, duocinonide, halcinonide, triamcinolone acetonide, and flurandrenolide, also undergo metabolism by routes that parallel that of cortisol metabolism. Unsymmetrical acetals such as budesonide are also metabolized by routes not available to the more metabolically stable symmetrical 16a,17a-isopropylidiene-dioxysubstituted compounds (desonide, flunisolide, and triamcinolone acetonide). Isozymes within the cytochrome P450 3A subfamily are thought to catalyze the metabolism of budesonide, resulting in formation of 16a-hydroxyprednisolone and 6P-hydroxybudesonide (19,20) (Fig. 3) in addition to the more common metabolic steps (oxidation via A6, reduction of A3, etc). 

Ilan, Z. and Z. Yaron. Interference of o,p DDD with interrenal function and cortisol metabolism in Sarotherodon aureus (Steindacher). J. Fish Biol. 22 657—669, 1983. 

Isotopic studies of steroid metabolism have been frequent since about 1954. The classical isotope dilution method was first introduced in the steroid field, using urinary metabolites, by Pearlman et al. (P5). In 1957 Pearlman (P4) pioneered the method of measuring the steady-state clearance from the blood of an isotopically labeled steroid administered by constant intravenous infusion. If a steady state is achieved, a knowledge of the rate of infusion of the isotopic steroid and its specific radioactivity, and measurement of the specific radioactivity of the steroid in the blood, yields the net flux of endogenous steroid entering the blood, which can usually be equated with its secretion rate. The same concepts were employed by Peterson (P5a, P7) in the investigation of cortisol metabolism. 

P3. Pasqualini, J. R., and Diczfalusy, E., Cortisol metabolism in the human foeto-placental unit at mid-pregnancy. Excerpta Med. Intern. Congr. Ser. 170, 30 (1968). 

Edwards OM, Courtenay-Evans RJ, Galley JM, Hunter J, Tait AD. Changes in cortisol metabolism following rifampicin therapy. Lancet 91A) ii, 549-51. 

Among sensitive species of freshwater teleosts, Cr" " concentrations of 16.0-21.0 xg/L in the medium resulted in reduced growth of rainbow trout and Chinook salmon (Oncorhynchus tshawytscha) fingerlings during exposure of 14-16 weeks, and altered plasma cortisol metabolism in rainbow trout after 7 days. Rainbow trout avoid water containing 28.0 xg Cr+ /L however, avoidance thresholds increased linearly if pre-exposed to... 

Although 17-ketosteroids are metabolites of cortisol and androgens, the excretion of 17-hydroxycorticoste-roids is ordinarily indicative of cortisol metabolism. It is possible to determine whether the low 17-ketoste-roid levels are of adrenal or extradrenal origin. ACTH injection restores 17-ketosteroid levels to normal in victims of adrenal insufficiency. 

Chronic consumption of GA has been reported to be associated with corticosteroidlike effects and changes in cortisol metabolism in tissues which may lead to hypermineralocorticoid-like effects such as electrolyte imbalance, hypertension, and depression of the renin-angiotensin-aldosterone system [1, 2]. However, the effects are reversible upon withdrawal of GA [1]. 

---