THE IN VIVO METABOLISM OF CORTISONE<sup>1</sup>

Burstein, Shlomo; Savard, Kenneth; Dorfman, Ralph I.

doi:10.1210/endo-52-4-448

Cited by 51 publications

(24 citation statements)

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“…This scheme is based on the work of a number of investigators (17,18,36) and has recently been reviewed by Bush (24). The position of allo-THF in this scheme is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Although a considerable amount of work has been done in isolating and identifying such urinary metabolites of cortisol as THF8 and THE (17)(18)(19)(20)(21)(22) and their interconversions (23)(24)(25), much less has been done to relate the quantitative transformations of these urinary metabolites from cortisol under normal and pathological conditions. In 1953, deCourcy, Bush, Gray, and Lunnon (26) reported daily excretion values for two chromatographically separated urinary steroids corresponding in migration rates to THF and THE, in 10 1 This work was suported in part by a grant from the Atomic Energy Commission.…”

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confidence: 99%

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Quantitative Determination of the Urinary Cortisolc Metabolites, “Tetrahydro F,” “Allo-Tetrahydro F” and “Tetrahydro E”: Effects of Adrenocorticotropin and Complex Trauma in the Human1

Gold¹,

Singleton²,

Macfarlane³

et al. 1958

J. Clin. Invest.

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Methods for the quantitative estimation of plasma cortisol concentration have been devised by Nelson and Samuels (1), Silber and Porter (2), and Peterson and Wyngaarden (3) who used the sulfuric acid-induced fluorescence developed by Sweat (4). Together with urinary procedures (5, 6) these techniques have been employed to determine the secretion of cortisol by the adrenal in normal and pathological conditions (7-9) and to evaluate the factors involved in the "removal" of cortisol from the plasma in surgery (10-13) and liver disease (14-16).Although a considerable amount of work has been done in isolating and identifying such urinary metabolites of cortisol as THF8 and THE (17-22) and their interconversions (23-25), much less has been done to relate the quantitative transformations of these urinary metabolites from cortisol under normal and pathological conditions. In 1953, deCourcy, Bush, Gray, and Lunnon (26) reported daily excretion values for two chromatographically separated urinary steroids corresponding in migration rates to THF and THE, in 10 1 This work was suported in part by a grant from the Atomic Energy Commission. It was sponsored and supported in part by the Subcommittee on Metabolism in Trauma, Advisory Committee on Metabolism, Office of the Surgeon General, Department of the Army, through a contract (DA-49-MD472) with Harvard University.The assistance of Winthrop Laboratories, Inc., and The Upjohn Co. is gratefully acknowledged.2 Present address: The Medical College of St. Bartholomew's Hospital, London. 3 Compounds referred to are the following: THF, tetrahydrocortisol (3a,11p,17a,21-tetrahydroxypregnan-20-one ); allo-THF (3a,1 1,l17a,21-tetrahydroxyallopregnan-20-one); THE, tetrahydrocortisone (3a,17a,21-trihydroxypregnan-11,20-dione); F, cortisol (llfi,17a,21-trihydroxypregnan-3,20-dione); E, cortisone (17a,21-dihydroxypregnan-3,11,20-trione).normal men. The mean values were 212 tg. per 24 hours for THF and 1.5 mg. per 24 hours for THE, giving a ratio for THF: THE of 0.14. Romanoff, Seelye, Rodriquez, and Pincus (27) have recently published quantitative data on the excretion of THF and THE combined with allo-THF (28, 29) in one group of normal men and in a group of schizophrenic men. There was no essential difference in the ratio of THF:(THE plus allo-THF) between the two groups of men, and the ratio was reported as approximately 1: 2. Cope and Hurlock (30) published data on the excretion of urinary THF and THE in several normal and surgical cases. Their results indicated increased excretion of these metabolites after surgery but did not show any other definite pattern of alteration of the metabolism of cortisol, although they state that "a tendency can be observed for tetrahydro-compound F excretion to rise more than does tetrahydrocortisone." In a preliminary report, Gold, Macfarlane, and Moore (31) showed that the relative proportions of the two urinary cortisol metabolites, THF and THE, were related to situations of "stress" and adrenocorticotropin (ACTH) administration. It is the purpo...

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“…This scheme is based on the work of a number of investigators (17,18,36) and has recently been reviewed by Bush (24). The position of allo-THF in this scheme is not clear.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Quantitative Determination of the Urinary Cortisolc Metabolites, “Tetrahydro F,” “Allo-Tetrahydro F” and “Tetrahydro E”: Effects of Adrenocorticotropin and Complex Trauma in the Human1

Gold¹,

Singleton²,

Macfarlane³

et al. 1958

J. Clin. Invest.

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“…Jayle, Desgrez, Serpicelli and Rozeg (11), Devis (12), Mills (13), and Appleby and Norymberski (14) found that the rise in urinary 17-OH-corticosteroids and 17-ketogenic steroids during pregnancy was of only moderate degree. Contradictory results have been obtained from studies of urinary 11-oxygenated 17-ketosteroids, the principal C19 metabolites of hydrocortisone (15). Dobriner, Lieberman, Rhoads and Taylor (16) and Davis and Plotz (17) reported that urinary 11-oxygenated 17-ketosteroids did not increase with advancing gestation, while Huis in't Veld (18) and Birke, Gemzell, Plantin and Robbe (19) claimed that these steroids were present in increased quantity in the third trimester.…”

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confidence: 99%

On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

Christy¹,

Wallace²,

W³

et al. 1959

J. Clin. Invest.

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The question of whether or not there is an increase in adrenal cortical secretion during pregnancy remains unsettled. Morphologic studies of the adrenal during gestation have revealed enlargement of the gland in some species (1) and no enlargement in others (2). In the human female, several groups of investigators have observed a progressive rise in the plasma 17-hydroxycorticosteroid (17-OH-corticosteroid) level during pregnancy (3-8). Paper chromatographic studies (9), confirmed in this laboratory (10), have indicated that the elevated plasma 17-OH-corticosteroid level is due to an increase in circulating hydrocortisone, and not to a nonspecific chromogen. Measurement of urinary 17-OH-corticosteroids has given equivocal results. Jayle, Desgrez, Serpicelli and Rozeg (11), Devis (12), Mills (13), and Appleby and Norymberski (14) found that the rise in urinary 17-OH-corticosteroids and 17-ketogenic steroids during pregnancy was of only moderate degree. Contradictory results have been obtained from studies of urinary 11-oxygenated 17-ketosteroids, the principal C19 metabolites of hydrocortisone (15). Dobriner, Lieberman, Rhoads and Taylor (16) crepancy between the finding of elevated plasma and of relatively normal urinary 17-OH-corticosteroid levels in pregnancy, Migeon, Bertrand and Wall investigated the rate of disappearance of injected 4-C14-hydrocortisone from plasma of pregnant women near term and found it to be delayed (20). These workers also observed a reduced rate of appearance of plasma and urine 17-OHcorticosteroid conjugates (glucuronides) after the administration of labeled hydrocortisone. These data suggested that the co-existence of high plasma (unconjugated) 17-OH-corticosteroid values and normal urine (unconjugated plus conjugated) 17-OH-corticosteroid values might be partly explained by the presence in both plasma and urine of a greater proportion of free hydrocortisone and a smaller proportion of conjugated hydrocortisone metabolites than normal (20). Devis (12) and Gray (21) have reported increased amounts of free 17-OH-corticosteroid in the urine of pregnant women. The present report describes studies upon the rate of hydrocortisone clearance from plasma in late pregnancy and in Laennec's cirrhosis, a condition in which hydrocortisone disposal rate is reportedly delayed (22)(23)(24). The data suggest that a delay in hydrocortisone clearance may not completely account for the elevated plasma 17-OHcorticosteroid levels observed in the pregnant state. MATERIALS AND METHODSPatients. Subjects were pregnant women in the third trimester of pregnancy who were not acutely ill and who showed no evidence of rheumatic heart disease, diabetes mellitus or pre-eclampsia. The women were hospitalized for premature rupture of the membranes or in anticipation of elective Caesarian section. Patients with Laennec's cirrhosis were six men and one woman with the typical clinical and laboratory features of parenchy-299

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“…The interstitial cells obtained from 5 to 6 rats were further fractionated by centrifugation on continuous Percoll gradients as previously reported (Browning et al, 1981 (Bedin et aL, 1988a (Payne and Kelch, 1975 (Lykkesfeldt et al, 1985b;Ruokonen et t aL, 1986;Bedin et aL, 1988b (Burstein and Dorfman, 1963), it is tempting to speculate that the enzymatic activity present in microsomes prepared from whole testis homogenates reflects the Leydig cell STS. Another, argument in favour of such a similarity between Leydig cells and whole testicular microsomes in terms of STS activity is that hCG treatment modulates the enzyme expression in the latter preparation in a manner similar to that previously reported for Leydig cells (Bedin et aL, 1988a (Payne and Kelch, 1975).…”

Section: Tissue Preparationsmentioning

confidence: 92%

Steroid sulfatase activity in homogenates, microsomes and purified Leydig cells from adult rat testis

Mouhadjer¹,

Bedin²,

Pointis³

1989

Reprod. Nutr. Dévelop.

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Summary -Steroid sulfatase (STS) activity was studied in the Long-Evans rat testis. The rate of dehydroepiandrosterone sulfate (DHA-S) hydrolysis determined in whole testis homogenates was low compared to that of the corresponding microsomal fractions, which was, in contrast, as high as that expressed in homogenates from purified Leydig cells. Such an increment in STS activity between total homogenate and the corresponding microsomes was not observed for the seminiferous tubules. The STS affinity reported for total testicular microsomes (K m = 3.47 ± 0.54 J.1M; mean ± SEM) was of the same magnitude as that previously reported for Leydig cells, but was about 3 times higher than that measured for whole testis homogenate (K, = 10.11 ± 0.92 J.1M). In vivo hCG treatment decreased the STS affinity in total testicular microsomes without affecting this kinetic parameter in whole testis homogenate. These data suggest that the steroid sulfatase expressed in total testicular microsomes (activity and regulation by hCG) could be considered as a good index of Leydig cell STS activity.steroid sulfatase -rat -testis -Leydig cells -microsomes Résumé -Activité stéroïde sulfatase dans des préparations purifiées de testicule de rat Long-Evans. L'activité stéroïde sulfatase (STS) a été étudiée dans le testicule de rat Long-Evans. Les homogénats de cellules de Leydig purifiées et la fraction microsomale isolée du testicule entier hydrolysent le sulfate de DHA à des taux équivalents; ces derniers sont nettement supérieurs au taux mesuré dans l'homogénat de testicule entier. L'enrichissement de l'activité STS constaté entre l'homogénat et la fraction microsomale correspondante n'est cependant pas retrouvé au niveau des tubes séminifères. La détermination des valeurs de K m (moyenne ± SEM) montre que I affinité de l'enzyme exprimée dans les microsomes de testicule entier (K m = 3,47 ± 0,54 P M) est du même ordre que celle précédemment rapportée pour les cellules de Leydig; elle est par ailleurs près de 3 fois supérieure à celle de l'enzyme présente dans l'homogénat de testicule entier (K m = 10,11 ± + 0,92 I cM). Le

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THE IN VIVO METABOLISM OF CORTISONE¹

Cited by 51 publications

References 0 publications

Quantitative Determination of the Urinary Cortisolc Metabolites, “Tetrahydro F,” “Allo-Tetrahydro F” and “Tetrahydro E”: Effects of Adrenocorticotropin and Complex Trauma in the Human1

Quantitative Determination of the Urinary Cortisolc Metabolites, “Tetrahydro F,” “Allo-Tetrahydro F” and “Tetrahydro E”: Effects of Adrenocorticotropin and Complex Trauma in the Human1

On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

Steroid sulfatase activity in homogenates, microsomes and purified Leydig cells from adult rat testis

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THE IN VIVO METABOLISM OF CORTISONE1

Cited by 51 publications

References 0 publications

Quantitative Determination of the Urinary Cortisolc Metabolites, “Tetrahydro F,” “Allo-Tetrahydro F” and “Tetrahydro E”: Effects of Adrenocorticotropin and Complex Trauma in the Human1

Quantitative Determination of the Urinary Cortisolc Metabolites, “Tetrahydro F,” “Allo-Tetrahydro F” and “Tetrahydro E”: Effects of Adrenocorticotropin and Complex Trauma in the Human1

On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

Steroid sulfatase activity in homogenates, microsomes and purified Leydig cells from adult rat testis

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THE IN VIVO METABOLISM OF CORTISONE¹