Isolation of Hydrocortisone and Corticosterone From Human Adrenal Vein Blood*

Romanoff, Elijah B.; Hudson, Perry B.; Pincus, Gregory

doi:10.1210/jcem-13-12-1546

Cited by 105 publications

(23 citation statements)

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“…Subsequently, hydrocortisone was found to be one of the principal corticoids in human adrenal gland perfusates (2) and in human peripheral blood (3). These observations strongly suggest that hydrocortisone may be the principal corticosteroid secreted by the adrenal cortex of man.…”

mentioning

confidence: 99%

The Miscible Pool and Turnover Rate of Hydrocortisone in Man

Peterson¹,

Wyngaarden²

1956

J. Clin. Invest.

174

111

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In 1948, Mason and Sprague (1) reported the isolation of hydrocortisone from the urine of a patient with Cushing's syndrome, and thus provided evidence that hydrocortisone was produced by the human adrenal cortex. Subsequently, hydrocortisone was found to be one of the principal corticoids in human adrenal gland perfusates (2) and in human peripheral blood (3). These observations strongly suggest that hydrocortisone may be the principal corticosteroid secreted by the adrenal cortex of man. Recent studies (4, 5) utilizing hydrocortisone-4-Cli have elucidated much new information regarding the metabolism and physiological disposition in man of this naturally occurring adrenal steroid.The availability of labeled hydrocortisone has made possible the direct estimation of the magnitude of the reservoir of hydrocortisone in the body, and the rate at which new, non-isotopic hydrocortisone is synthesized in the body and enters the reservoir. This report is concerned with the experimental determination of the magnitude of the miscible pool of hydrocortisone and the rate of its turnover in man. These estimations depend upon serial measurements of the specific activity of circulating hydrocortisone after the infusion of trace quantities of hydrocortisone4-0C1 and analyses of these data utilizing conventional turnover calculations (6, 7). Observations have been made in normal subjects, and subjects receiving adrenocorticotropin and A1 cortisone (prednisone). MATERIALS AND METHODSNine normal subjects (7 male and 2 female) were used for these studies. Each subject received 1 to 2.5 microcuries of hydrocortisone-4-C' dissolved in 2 to 5 ml. of 10 per cent ethanol in sterile distilled water. The steroid was administered intravenously in the fasting state in the morning over a period of approximately 3 minutes. Heparinized blood samples (40 to 60 ml. each) were collected at 30 to 40-minute intervals after injection of the isotope.Procedure for determination of sPecific activity of circulating hydrocortisone Twenty-five to 35 ml. of plasma were extracted gently for 10 minutes on a rotator (Arthur H. Thomas Co., Catalog No. 3623) in a 700-ml. Erlenmeyer flask with 5 volumes of dichloromethane (purified by passing through a column of silica gel [5]).The plasma and solvent were gently transferred to a 200-ml. ground-glass stoppered cylinder, and the plasma removed by aspiration.The dichloromethane extract was washed successively with 'A volume of 0.01 N sodium hydroxide, 'As volume of 0.1 M acetic acid, and X5 volume of water.

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mentioning

confidence: 99%

The Miscible Pool and Turnover Rate of Hydrocortisone in Man

Peterson¹,

Wyngaarden²

1956

J. Clin. Invest.

174

111

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“…2 The dose was 8 mg of cortisol (calculated as milligrams of the free steroid) per kg body weight. The amount chosen was large 1) in a deliberate attempt to achieve high, readily measurable concentrations of cortisol, 2) in order to approximate pharmacologic doses, and 3) in order to achieve high plasma concentrations of glucuronides of cortisol metabolites so as to afford the best possible opportunity for these glucuronides to penetrate the blood-CSF barrier.…”

Section: Methodsmentioning

confidence: 99%

“…Cortisol,' one of the principal circulating adrenal cortical steroids of man (1,2) enters the CSF (3)(4)(5), but little is known about the rate at which it passes into the CSF or what factors regulate its passage. Although the relationship of CSF to the extracellular fluid of the brain is complex, it is generally accepted that the two compartments are in equilibrium, and that the blood-CSF and blood-brain barriers do not differ qualitatively in their respective permeability characteristics (6,7).…”

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confidence: 99%

Studies of the Blood-Cerebrospinal Fluid Barrier to Cortisol in the Dog*

Christy¹,

Fishman²

1961

J. Clin. Invest.

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This study was undertaken to investigate the entry of administered cortisol and one of its metabolic products into the cerebrospinal fluid (CSF) of dogs under a variety of conditions. Cortisol,' one of the principal circulating adrenal cortical steroids of man (1, 2) enters the CSF (3-5), but little is known about the rate at which it passes into the CSF or what factors regulate its passage. Although the relationship of CSF to the extracellular fluid of the brain is complex, it is generally accepted that the two compartments are in equilibrium, and that the blood-CSF and blood-brain barriers do not differ qualitatively in their respective permeability characteristics (6, 7). The data of this study on the entry of cortisol into CSF can therefore be considered relevant to the problem of penetration of cortisol into the brain. This is of some clinical importance with respect to the known effects of cortisol upon brain metabolism; e.g., upon seizure threshold and emotional state (8).There are abundant data which show that the rate of entry of many substances into the CSF is determined by certain of their physical and chemical properties. These properties are solubility in lipid solvents, binding to plasma protein, molecular size, and in the case of salts of weak acids and bases, pK (6, 7, 9). Since neutral steroids have no pK, and molecular size is not an important determinant of rate of entry into the CSF except with substances of very high molecular weight (6. 7), only lipid solubility and binding to plasma

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“…Corticosterone is the next most abundant compound (114,115). Progesterone was shawn to be converted to 18-hydroxycorticosterone in human adrenals (108), and was reported'to be present in larger amounts than te -26 -aldosterone (117).…”

Section: )mentioning

confidence: 99%