Corticosteroid metabolism in isolated rat kidney in vitro

Hierholzer, Klaus; Sch�nesh�fer, M.; Siebe, H.; Tsiakiras, D.; Weskamp, P.; Lichtenstein, I.

doi:10.1007/bf00587533

Cited by 26 publications

(1 citation statement)

References 26 publications

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“…In clinical studies these licorice-derived inhibitors induce mineralocorticoid effects, with little or no change in the cortisone/cortisol metabolite ratio (23,28,29). Ring A reduction, a step known to occur in normal kidney (30,31), is also inhibited by glycerrhetinic acid (32). This reaction could be impaired in the carbenoxolone model and in the type 2 variant.…”

Section: Licorice-derived Inhibitors Of the Peripheral Metabolism Of mentioning

confidence: 98%

Pathogenesis of the Type 2 Variant of the Syndrome of Apparent Mineralocorticoid Excess*

Ulick

Tedde

Mantero

1990

The Journal of Clinical Endocrinology & Metabolism

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The syndrome of apparent mineralocorticoid excess, which is not a primary disorder of the adrenal cortex, describes the association of an unexplained hypermineralocorticoid state with a decreased rate of peripheral 11 beta-hydroxydehydrogenation of cortisol to cortisone. Studies in this syndrome have led to the hypothesis that peripheral cortisol inactivation is the normal mechanism permitting specific mineralocorticoid recognition. This view reconciled developing evidence that the mineralocorticoid receptor itself could not distinguish between mineralocorticoids and glucocorticoids. The syndrome occurs in two forms. In both forms there is decreased turnover of a normal level of plasma cortisol, consistent with the view that delayed removal of the glucocorticoid from strategic receptor sites unmasks its potential mineralocorticoid agonism. In the type 1 variant, impaired 11 beta-hydroxydehydrogenation is reflected by an elevated cortisol/cortisone metabolite ratio. In three patients with the type 2 variant, this ratio was normal, suggesting that the rate of 11 beta-hydroxydehydrogenation was unimpaired. The hypertension and hypokalemic alkalosis of both forms are improved by spironolactone, but patients with the type 2 variant have responded somewhat better to the suppression of cortisol by dexamethasone.

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Section: Licorice-derived Inhibitors Of the Peripheral Metabolism Of mentioning

confidence: 98%

Pathogenesis of the Type 2 Variant of the Syndrome of Apparent Mineralocorticoid Excess*

Ulick

Tedde

Mantero

1990

The Journal of Clinical Endocrinology & Metabolism

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Aldosterone: Renal Action and Physiological Effects

Johnston

Welch

Cain

et al. 2023

Comprehensive Physiology

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Aldosterone exerts profound effects on renal and cardiovascular physiology. In the kidney, aldosterone acts to preserve electrolyte and acid-base balance in response to changes in dietary sodium (Na + ) or potassium (K + ) intake. These physiological actions, principally through activation of mineralocorticoid receptors (MRs), have important effects particularly in patients with renal and cardiovascular disease as demonstrated by multiple clinical trials. Multiple factors, be they genetic, humoral, dietary, or otherwise, can play a role in influencing the rate of aldosterone synthesis and secretion from the adrenal cortex. Normally, aldosterone secretion and action respond to dietary Na + intake. In the kidney, the distal nephron and collecting duct are the main targets of aldosterone and MR action, which stimulates Na + absorption in part via the epithelial Na + channel (ENaC), the principal channel responsible for the fine-tuning of Na + balance. Our understanding of the regulatory factors that allow aldosterone, via multiple signaling pathways, to function properly clearly implicates this hormone as central to many pathophysiological effects that become dysfunctional in disease states. Numerous pathologies that affect blood pressure (BP), electrolyte balance, and overall cardiovascular health are due to abnormal secretion of aldosterone, mutations in MR, ENaC, or effectors and modulators of their action. Study of the mechanisms of these pathologies has allowed researchers and clinicians to create novel dietary and pharmacological targets to improve human health. This article covers the regulation of aldosterone synthesis and secretion, receptors, effector molecules, and signaling pathways that modulate its action in the kidney. We also consider the role of aldosterone in disease and the benefit of mineralocorticoid antagonists.

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Bile acids and their amidates inhibit 11?-hydroxysteroid dehydrogenase obtained from rat kidney

1991

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Recently it has been demonstrated that interaction of corticosteroids with extraadrenal target cells can effectively be modulated by metabolic transformation of the steroid hormone. As far as 11-hydroxylated glucocorticoids are concerned 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is the most important enzyme charged with target cell metabolism. Inhibition of 11 beta-HSD function either by genetically transmitted deficiency or by exogenous enzyme inhibitors causes severe pathophysiological derangements, which result in a syndrome of "apparent mineralocorticoid excess". In the present paper we have tested whether or not endogenous inhibitors of this enzyme system might exist. The effects of the main naturally occurring mono-, di-, and trihydroxylated bile acids in man on 11 beta-HSD have been studied in in vitro experiments. Using rat renal microsomes it could be demonstrated that unconjugated bile acids of all three classes as well as the corresponding glycine and taurine amidates effectively inhibit oxidative as well as reductive activity of 11 beta-HSD, with lithocholic acid and chenodeoxycholic acid being the most potent compounds. It is concluded that bile acids are potent endogenous inhibitors of 11 beta-HSD and, therefore, could participate in abnormalities of cortisol metabolism observed in liver cirrhosis and extrahepatic biliary obstruction and, possibly, after ingestion of bile acids.

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Corticosteroid metabolism in isolated rat kidney in vitro

Cited by 26 publications

References 26 publications

Pathogenesis of the Type 2 Variant of the Syndrome of Apparent Mineralocorticoid Excess*

Pathogenesis of the Type 2 Variant of the Syndrome of Apparent Mineralocorticoid Excess*

Aldosterone: Renal Action and Physiological Effects

Bile acids and their amidates inhibit 11?-hydroxysteroid dehydrogenase obtained from rat kidney

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