Conversion of Cortisone to Compound F

Amelung, D; Hübener, H. J.; Róka, L; Meyerheim, G.

doi:10.1210/jcem-13-9-1125

Cited by 66 publications

(29 citation statements)

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“…Previous investigators have shown by perfusion of the liver (11,12) and with liver slices (13,14) and liver homogenates (15,16), that cortisone is converted to hydrocortisone. Also, studies of urinary steroid metabolites in man following the administration of cortisone have demonstrated this conversion (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

The Physiological Disposition and Metabolic Fate of Cortisone in Man

Peterson¹,

Pierce²,

Wyngaarden³

et al. 1957

J. Clin. Invest.

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In an earlier paper we described studies on the physiological disposition and metabolic fate of hydrocortisone in man (1). This paper describes similar studies on cortisone. Although contributing very little to the body pool of adrenal cortical steroids, cortisone has been used extensively as a therapeutic agent, and it was therefore of interest to compare its metabolism with that of hydrocortisone. Large doses of cortisone and hydrocortisone were administered intravenously and rates of disappearance from the plasma determined in normal subjects and in patients with liver disease, myxedema, thyrotoxicosis, and rheumatoid arthritis. Trace quantities of cortisone-4-C" and hydrocortisone-4-C" were employed in certain studies. From these studies, information was obtained regarding rate of metabolic transformation, rate of absorption, rates and routes of excretion of cortisone and its metabolites, and, to some extent, the identity and amount of these metabolites. Information was also obtained on the in vivo conversion of cortisone to hydrocortisone. MATERIALS AND METHODSAdministration of steroid. The steroids were dissolved in 25 ml. ethanol and added to 500 ml. of sterile five per cent dextrose in water. This solution was administered intravenously over a period of 10 to 20 minutes. For oral or intramuscular administration the steroids were suspended in saline. Cortisone-4-C" was administered intravenously in trace quantities in a small volume of five per cent ethanol in water over a period of 3 to 5 minutes, or mixed with carrier cortisone and given in 500 ml. of three per cent ethanol in five per cent dextrose in sterile distilled water. Following the administration of the steroids, blood samples were drawn in heparinized syringes every 20 or 30 minutes for 2 hours-or more.Urine samples were collected and preserved by freezing.Methods of assay. The extraction procedures for the steroids in plasma and urine were the same as those de-

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Section: Discussionmentioning

confidence: 99%

The Physiological Disposition and Metabolic Fate of Cortisone in Man

Peterson¹,

Pierce²,

Wyngaarden³

et al. 1957

J. Clin. Invest.

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“…First, Burton et al (106) demonstrated cortisone metabolism to other steroids including cortisol in humans. Then in 1953, Amelung et al (21) in Frankfurt administered cortisone to rats in vivo and incubated cortisone with homogenates of various tissues in vitro and found conversion to cortisol. The activity, localized to microsomes, was highest in liver with lower amounts in kidney and muscle.…”

Section: A the Historical Contextmentioning

confidence: 99%

“…11␤-HSD1 was initially discovered, characterized, purified, cloned, and most highly expressed in liver (4,21,378,478,695). Despite this head start, and the absence of 11␤-HSD2, the function of 11␤-HSD1 in hepatocytes and especially in liver in vivo is far from completely understood.…”

Section: A Livermentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

713

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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“…11-␤-Hydroxysteroid dehydrogenase type II (HSD2) is an enzyme that catalyzes the conversion of active cortisol to inert cortisone (1). This conversion plays an important role in MR-expressing cells by preventing binding of cortisol (a glucocorticoid) to the MR and allowing aldosterone to bind in its place.…”

mentioning

confidence: 99%

Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone

Koneru

Bathina

Cherry

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Koneru B, Bathina CS, Cherry BH, Mifflin SW. Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone. Am J Physiol Regul Integr Comp Physiol 306: R61-R66, 2014. First published November 20, 2013 doi:10.1152/ajpregu.00434.2013.-The purpose of this study was to determine whether neurons within the nucleus tractus solitarius (NTS) that express the mineralocorticoid receptor (MR) play a role in aldosterone stimulation of salt intake. Adult Wistar-Kyoto (WKY) rats received microinjections into the NTS of a short-hairpin RNA (shRNA) for the MR, to site specifically reduce levels of the MR by RNA interference (shRNA; n ϭ 9) or scrambled RNA as a control (scRNA; n ϭ 8). After injection of the viral construct, aldosteronefilled osmotic minipumps were implanted subcutaneously and connected to a cannula extending into the fourth ventricle to infuse aldosterone at a rate of 25 ng/h. Before and after surgeries, rats had ad libitum access to normal sodium (0.26%) rat chow and two graduated drinking bottles filled with either distilled water or 0.3 M NaCl. Before the surgeries, basal saline intake was 1.6 Ϯ 0.6 ml in the scRNA group and 1.56 Ϯ 0.6 ml in the shRNA group. Twenty-four days postsurgery, saline intake was elevated to a greater extent in the scRNA group (5.9 Ϯ 1.07 ml) than in the shRNA group (2.41 Ϯ 0.6 ml). Post mortem immunohistochemistry revealed a significant reduction in the number of NTS neurons exhibiting immunoreactivity for MR in shRNA-injected rats (23 Ϯ 1 cells/section) versus scRNAinjected rats (33 Ϯ 2 cells/section; P ϭ 0.008). shRNA did not alter the level of 11-␤-hydroxysteroid dehydrogenase type II (HSD2) protein in the NTS as judged by the number of HSD2 immunoreactive neurons. These results suggest that fourth ventricular infusions of aldosterone stimulate saline intake, and that this stimulation is at least in part mediated by hindbrain NTS neurons that express MR.

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Conversion of Cortisone to Compound F

Cited by 66 publications

References 0 publications

The Physiological Disposition and Metabolic Fate of Cortisone in Man

The Physiological Disposition and Metabolic Fate of Cortisone in Man

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Mineralocorticoid receptor in the NTS stimulates saline intake during fourth ventricular infusions of aldosterone

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