The Secretion and Disposition of Cortisol During Pregnancy*

Cohen, May; Stiefel, M.; Reddy, William J.; Laidlaw, J. C.

doi:10.1210/jcem-18-10-1076

Cited by 92 publications

(15 citation statements)

References 3 publications

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“…The latter biologic potential of transcortin has been demonstrated in the experiments presented. In previously published investigations it was shown that cortisol is metabolized at a greatly reduced rate in subjects with high concentrations of plasma transcortin (4,(6)(7)(8). These results were interpreted as indicating that the much slower metabolism of cortisol was due to its being bound to transcortin and thus rendered unavailable for catabolism by the liver.…”

Section: Discussionmentioning

confidence: 96%

“…Using these indirect evidences, we have postulated that transcortinbound cortisol is 1) biologically inactive and 2) unavailable for catabolism. The first hypothesis explains the lack of hypercorticism in face of high cortisol levels in pregnancy and in estrogentreated subjects, and the second hypothesis the slower metabolism of cortisol in the above subjects (4)(5)(6)(7)(8). The verification of the first hypothesis has recently been published from our laboratory and is based on the observation that transcortin prevents glycogen deposition in adrenalectomized mice treated with cortisol (9).…”

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confidence: 98%

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Transcortin: A Corticosteroid-Binding Protein of Plasma. V. In Vitro Inhibition of Cortisol Metabolism*

Sandberg¹,

Slaunwhite²

1963

J. Clin. Invest.

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Elevated concentrations of plasma transcortin have been shown to exist during pregnancy or after the administration of estrogens and to be accompanied by almost concomitant increases in the levels of plasma cortisol (1-4).1 The latter change has been ascribed to the higher transcortin capacity to bind cortisol. Using these indirect evidences, we have postulated that transcortinbound cortisol is 1) biologically inactive and 2) unavailable for catabolism. The first hypothesis explains the lack of hypercorticism in face of high cortisol levels in pregnancy and in estrogentreated subjects, and the second hypothesis the slower metabolism of cortisol in the above subjects (4-8). The verification of the first hypothesis has recently been published from our laboratory and is based on the observation that transcortin prevents glycogen deposition in adrenalectomized mice treated with cortisol (9). In this paper we wish to report evidence in support of the second hypothesis, i.e., that transcortin prevents the catabolism of cortisol by human or rat liver homogeniates or microsomes. METHODS AND MATERIALSHuman liver was obtained at operation and processed immediately at 50 C. Human or rat liver homogenates (10 per cent) were made in 0.05 M phosphate buffer at pH 7.4. For the isolation of microsomes a 10 per cent homogenate in 0.25 M sucrose was prepared by hand usinig a Potter-Elvehj em homogenizer. After sedimentation of the nuclei and mitochondria, the microsomes were collected as sediment at 104,000 X G. The microsomes * Presented at the Fifty-fourth Annual Meeting of the American Society for Clinical Investigation (Section on Endocrinology), Atlantic City, N. J., April, 1962. This study has been supported in part by Grant A-1240 from the National Institutes of Health.1 The following abbreviations have been employedcortisol (F): 11,6,17a,21-trihydroxy-4-pregnene-3,20-dione; dihydrocortisol: 11 ,17a,21-trihydroxy-pregnane-3,20-dione; tetrahydrocortisol: 3a,11,6,17a,21-tetrahydroxy-pregnane-20-one; TPNH: reduced triphosphopyridine nucleotide; HSA: human serum albumin.were then suspended in phosphate buffer. The homogenates or microsomes were incubated with 1.5 ,tg of 4-C14-cortisol (13.7 tuc per mg) and one ml of 2 X 10-3M TPNH (generated enzymatically immediately before use) (10) in a total volume of 8 ml for 30 minutes at 37.50 C. At the end of the incubation the contents of each flask were extracted twice with 3 volumes of dichloromethane. Purification of transcortin. Over 600 ml of plasma from subjects treated with estrogens was dialyzed against 2 volumes of water overnight in the cold room. After adjusting the pH of the dialyzed plasma to 5.0, it was clarified by centrifugation and then placed on a 5 X 35 cm column of diethylaminoethylcellulose (DEAEC), which had been previously conditioned to 0.05 M sodium chloride at pH 5.0. After the plasma had all entered the resin, the column was washed with 0.05 Ml sodium chloride, pH 5.0, until the optical density of the eluate at 280 myt fell to 0.6. A gradient was then started...

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 98%

Transcortin: A Corticosteroid-Binding Protein of Plasma. V. In Vitro Inhibition of Cortisol Metabolism*

Sandberg¹,

Slaunwhite²

1963

J. Clin. Invest.

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“…Decreased rates of metabolism of C14-cortisol have been shown to occur in pregnant women (12,13). It should be emphasized, however, that transcortin may be only one of the factors influencing rates of cortisol metabolism and that the other factors (state of liver function, metabolic rate and so forth) probably play important roles.…”

Section: Discussionmentioning

confidence: 99%

Transcortin: A Corticosteroid-Binding Protein of Plasma. Ii. Levels in Various Conditions and the Effects of Estrogens *

Sandberg¹,

Slaunwhite²

1959

J. Clin. Invest.

237

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“…The elevated levels of plasma 17-OHCS are associated with an augmented response of plasma levels of these steroids to exogenous adrenocorticotropic hormone (ACTH) and with a marked delay in the rate of clearance of exogenous cortisol from plasma (2). The last trimester of pregnancy is associated with similar changes in levels of plasma 17-OHCS and in their response to exogenous ACTH (3)(4)(5)(6)(7)(8)(9). In the last trimester of pregnancy there is a variable increase in urinary 17-OHCS excretion, a decrease in the rate of clearance of exogenous cortisol from plasma (9)(10)(11), a decrease in the rate of clearance of exogenous tetrahydrocortisone from plasma (11) and an increase in corticosteroid-binding protein (12).…”

mentioning

confidence: 99%

“…The last trimester of pregnancy is associated with similar changes in levels of plasma 17-OHCS and in their response to exogenous ACTH (3)(4)(5)(6)(7)(8)(9). In the last trimester of pregnancy there is a variable increase in urinary 17-OHCS excretion, a decrease in the rate of clearance of exogenous cortisol from plasma (9)(10)(11), a decrease in the rate of clearance of exogenous tetrahydrocortisone from plasma (11) and an increase in corticosteroid-binding protein (12). The apparently normal adrenal status of pregnant women and of patients treated with estrogens for long periods of time suggests that the administration of estrogens to man elevates plasma 17-OHCS levels by altering the normal metabolism of endogenous cortisol by a mechanism similar to that seen in pregnancy.…”

mentioning

confidence: 99%

Studies on the Mechanism of the Plasma 17-Hydroxycorticosteroid Elevation Induced in Man by Estrogens*

Wallace¹,

Carter²

1960

J. Clin. Invest.

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The administration of estrogens to man produces sustained elevation above normal levels of plasma (1, 2). The elevated levels of plasma 17-OHCS are associated with an augmented response of plasma levels of these steroids to exogenous adrenocorticotropic hormone (ACTH) and with a marked delay in the rate of clearance of exogenous cortisol from plasma (2). The last trimester of pregnancy is associated with similar changes in levels of plasma 17-OHCS and in their response to exogenous ACTH (3-9). In the last trimester of pregnancy there is a variable increase in urinary 17-OHCS excretion, a decrease in the rate of clearance of exogenous cortisol from plasma (9-11), a decrease in the rate of clearance of exogenous tetrahydrocortisone from plasma (11) and an increase in corticosteroid-binding protein (12). The apparently normal adrenal status of pregnant women and of patients treated with estrogens for long periods of time suggests that the administration of estrogens to man elevates plasma 17-OHCS levels by altering the normal metabolism of endogenous cortisol by a mechanism similar to that seen in pregnancy. Studies have been made of urinary 17-OHCS excretion, of clearance of tetrahydrocortisone from plasma, and of plasma corticosteroid-binding protein after the administration of estrogens to man. MATERIALS AND METHODSThe patients studied were primarily adult females ranging in age from 37 to 75 years, all of whom either had been surgically castrated or were at least 3 years past a spontaneous menopause. A number of these subjects were patients with metastatic carcinoma of the * This work was supported in part by a research grant from The National Cancer Institute, Bethesda, Md. breast. One male was studied during recovery from a myocardial infarction.After appropriate control studies, the patients were treated for periods of 2 weeks to 6 months with either oral ethinyl estradiol (Estinyl), diethylstilbestrol or conjugated equine estrogens (Premarin). Only doses of these preparations which uniformly elevated plasma 17-OHCS levels above normal were used in the studies (Table I). Ethinyl estradiol 0.1 and 0.5 mg, diethylstilbestrol 15 mg, and Premarin 10 mg, daily by mouth, all caused significant increases in the levels of plasma 17-OHCS.The effect of oral ethinyl estradiol, 0.5 mg daily, on urinary excretion of free and total 17-OHCS and of 17-ketosteroids was studied. Twenty-four hour urinary excretion of steroids was determined in each patient before estrogen therapy and again after plasma 17-OHCS

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The Secretion and Disposition of Cortisol During Pregnancy*

Cited by 92 publications

References 3 publications

Transcortin: A Corticosteroid-Binding Protein of Plasma. V. In Vitro Inhibition of Cortisol Metabolism*

Transcortin: A Corticosteroid-Binding Protein of Plasma. V. In Vitro Inhibition of Cortisol Metabolism*

Transcortin: A Corticosteroid-Binding Protein of Plasma. Ii. Levels in Various Conditions and the Effects of Estrogens *

Studies on the Mechanism of the Plasma 17-Hydroxycorticosteroid Elevation Induced in Man by Estrogens*

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