6β-Hydroxycortisol AND OTHER POLAR CORTICOSTEROIDS: MEASUREMENT AND SIGNIFICANCE IN HUMAN URINE*†

Frantz, Andrew G.; Katz, Fred H.; Jailer, Joseph W.

doi:10.1210/jcem-21-10-1290

Cited by 118 publications

(18 citation statements)

References 12 publications

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“…As demonstrated subsequently in the studies with cortisol-4-C14, this polar unknown compound was a metabolite of cortisol, but its identification has not been accomplished. Incubation of several urine samples with f-glucuronidase before extraction did not increase the yield of 6-OHF, which is similar to the observation of Frantz and associates (16).…”

Section: Methodssupporting

confidence: 89%

“…Testosterone depresses cortisol A-ring reduction (28)(29)(30) but does not increase 6-OHF excretion (11). ACTH has been reported to enhance 6-OHF excretion to some degree (16). In the present study, however, little change was noted in the ratio of 6-OHF: 17-OHCS after ACTH when subjects were not receiving DPH.…”

Section: Discussioncontrasting

confidence: 74%

“…This indicates an inhibition of ,B-glucuronidase by DPH or its major metabolite, 5-(p-hydroxyphenyl) -5-phenylhydantoin (24), which is conjugated with glucuronic acid (25). Although the mechanism of inhibition was not studied, it is conceivable that it might be a competitive one as noted with the glucuronide of acetylsalicylic acid (26 (11,12,16,23,27) and by Ulstrom, Colle, Burley, and Gunville (13). The latter group noted that 6-OHF was a major metabolite of cortisol in newborn infants.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Werk¹,

MacGee²,

Sholiton³

1964

J. Clin. Invest.

164

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During a study of cortisol metabolism in advanced cancer and other disease states (1), we observed in patients receiving DPH 1 therapy for convulsive seizures an abnormal pattern of excretion of cortisol metabolites in urine. This abnormal pattern was characterized by increased urinary output of the polar unconjugated metabolite 6-OHF, suggesting an interference with extraadrenal metabolism of cortisol by DPH. We =5,5'-diphenylhydantoin; 6-hydroxycortisol (6 -OHF) = 6a (/3), 11,/, 17a, 21 -tetrahydroxy -4 -pregnene-3,20 -dione; 17-OHCS = 17-hydroxycorticosteroids; ACTH = adrenocorticotrophic hormone; methopyrapone (Metopirone, Ciba Pharmaceutical Co., Summit, N. J.) =2-methyl-1,2-di-(3-pyridyl)-1-propanone. Tetrahydro derivatives: THF (tetrahydrocortisol) = 3a,11,, 17a,21-tetrahydroxy-5/8-pregnan-20-one; allo-THF (allotetrahydrocortisol) = 3a,11/3,17a,21-tetrahydroxy-5a-?pregnan-20-one; THE (tetrahydrocortisone) = 3a,17a,21-trihydroxy-5p-pregnan-11,20-dione. Cortol = 3a,11,8,17a,20a (/3),21-pentahydroxy-5/3-pregnane; cortolone = 3a,17a,20a (/3) ,21-tetrahydroxy-5/8-pregnan-11-one; 17-KS = 17-ketosteroids; 1 1-hydroxyetiocholanolone = 3a,1j1/-dihydroxy-5,B-androstan-17-one; dehydroisoandrosterone = 3/3-hydroxy-5-androstene-17-one; TPNH = reduced triphosphopyridine nucleotide; o,p'DDD = 2,2-bis (2-chlorophenyl,4-chlorophenyl) 1,1-dichloroethane. since a) adrenal hypertrophy was observed in intact rats and b) in adrenalectomized rats treated with DPH a more profound decrease in brain excitability was demonstrated than in intact rats. Goncharov has observed that acute administration of DPH to dogs and guinea pigs increases adrenocortical output of cortisol (3). Reports by Staple (4) and Bonnycastle and Bradley (5) have, however, indicated an inhibition of pituitary-adrenal secretion after chronic DPH treatment of mice and rats.In humans also cortisol has been shown to enhance brain excitability (6). After chronic DPH therapy to patients, excretion of corticosteroids in urine is reported to decrease (7, 8) after an initial increase (7). These findings have led to the suggestion that the decrease in brain excitability induced by DPH might be mediated partially through adrenocortical suppression. However, levels of 17-OHCS in plasma from patients treated with DPH are usually normal (8, 9), as are responses to ACTH (8, 9) and rates of disappearance from plasma of infused cortisol (8). These observations detract from the possibility that direct adrenocortical suppression plays a significant role in therapeutic effectiveness of DPH. Recently, however, Krieger has demonstrated that control subjects treated with DPH manifest a reduced response in the methopyrapone test, which suggests an interference with ACTH release (10).2) The increased excretion of 6-OHF produced by DPH appears to be similar to that we have observed in patients with advanced cancer and certain terminal illnesses (1) as well as to that reported after estrogen therapy (11), during pregnancy (12), and in newborn infants (13).Thus we hoped that furthe...

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Section: Methodssupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Werk¹,

MacGee²,

Sholiton³

1964

J. Clin. Invest.

164

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“…The eluates from the last chromatography were dried in a liquid scintillation counting vial and 10 ml of a toluene solution containing 3%o PPO and 0.01%o POPOP was added for counting. An aliquot of the authentic cortisol that had been acetylated with the tritiated acetic anhydride was also counted at the same time, and another aliquot quantitated by the Porter-Silber reaction (11) to determine the precise molar specific activity of-the acetic anhydride.…”

Section: Methodsmentioning

confidence: 99%

Parotid fluid cortisol and cortisone

Katz¹,

Shannon²

1969

J. Clin. Invest.

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A B S T R A C T Parotid fluid corticosteroids, substantially comprised of cortisol and cortisone, were previously demonstrated to rise to far greater levels 4 hr after administration of ACTH than they did in the third trimester of pregnancy, although the plasma total corticosteroid concentrations were similar in these two states. It was therefore suggested that only nonproteinbound corticosteroid gains access to parotid fluid. In the present study parotid fluid cortisol and cortisone and plasma dialyzable cortisol concentrations have been measured in normal men before and 2 hr after 40 U ACTH, and, in another group, before and after 10 days of diethystilbestrol (5 mg daily). Total plasma cortisol rose from a mean of 6.3 to 17.9 ,ug/100 ml after ACTH and from 14.6 to 39.4 mg/100 ml after the estrogen. However parotid fluid cortisol plus cortisone rose from 0.8 to 2.6 ,ug/100 ml after ACTH and to only 2.2 after estrogen. This rise resembled that of the plasma dialyzable cortisol (control 0.4, ACTH 1.8, estrogen 1.2 ug/ 100 ml) rather than the increase in total plasma cortisol which was over twice as high after estrogen as after ACTH. Thus parotid fluid corticosteroids seem to be a good measure of nonprotein-bound corticosteroid, the cortisol available to the cell. The total amount of cortisol plus cortisone excreted is approximately constant, independent of parotid fluid flow rate. Cortisone exceeds cortisol in parotid fluid in the basal state, but after ACTH the situation is reversed.

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“…One such is 6,B-hydroxycortisol, normally only a minor metabolite of cortisol, forming up to 6% of total urinary oxogenic steroids (Frantz et al, 1961). Various inducers, including phenobarbitone (Burstein and Klaiber, 1965), phenytoin (Werk et 01., 1964), and DDT (Poland et 01., 1970) have been shown to increase the excretion of 6,B-hydroxycortisol in man.…”

Section: Changes In Endogenous Substances As Indices Of Microsomal Enmentioning

confidence: 99%

Enzyme Induction by Drugs

Marshall

1978

Ann Clin Biochem

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SUMMARY The properties of the hepatic microsomal, drug detoxicating, enzyme system are reviewed with particular reference to its inducibility. Induction is modified by various factors of which the diet is particularly important. A theoretical model system for induction has been proposed and this is discussed. There are a number of methods for assessing microsomal enzyme induction in man, none of which is ideal. Nevertheless, induction is a well recognised phenomenon in man and has a bearing on the metabolism of a number of endogenous substances. The effect of induction on steroid metabolism and the relationship between inducers, vitamin D, and metabolic bone disease is discussed. Bilirubin metabolism is affected by changes in microsomal enzyme activity and inducers have been used therapeutically in some cases of hyperbilirubinaemia. The relationship between drugs and the hepatic porphyrias is reviewed. The hepatic microsomal enzyme system is but one of many inducible enzymes and the role of induction in general in metabolic regulation is emphasised.

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6β-Hydroxycortisol AND OTHER POLAR CORTICOSTEROIDS: MEASUREMENT AND SIGNIFICANCE IN HUMAN URINE*†

Cited by 118 publications

References 12 publications

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Effect of Diphenylhydantoin on Cortisol Metabolism in Man *

Parotid fluid cortisol and cortisone

Enzyme Induction by Drugs

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