Mineralocorticoid excess and inhibition of 11 β‐hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome

Walker, Brian R.; Campbell, Jill C.; Fraser, Robert; Stewart, Paul M.; Edwards, C. R. W.

doi:10.1111/j.1365-2265.1992.tb01478.x

Cited by 181 publications

(132 citation statements)

References 40 publications

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“…The plasma levels of the inactive form, cortisone, are w50-100 nM, and the hormone is largely unbound to plasma proteins (Walker et al 1992). Local conversion between active and inactive forms is catalysed by 11b-hydroxysteroid dehydrogenase (11b-HSD).…”

Section: Cellular Mechanisms Of Gc Actionmentioning

confidence: 99%

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

Rafacho¹,

Ortsäter²,

Nadal³

et al. 2014

Journal of Endocrinology

184

114

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Glucocorticoids (GCs) are broadly prescribed for numerous pathological conditions because of their anti-inflammatory, antiallergic and immunosuppressive effects, among other actions. Nevertheless, GCs can produce undesired diabetogenic side effects through interactions with the regulation of glucose homeostasis. Under conditions of excess and/or long-term treatment, GCs can induce peripheral insulin resistance (IR) by impairing insulin signalling, which results in reduced glucose disposal and augmented endogenous glucose production. In addition, GCs can promote abdominal obesity, elevate plasma fatty acids and triglycerides, and suppress osteocalcin synthesis in bone tissue. In response to GC-induced peripheral IR and in an attempt to maintain normoglycaemia, pancreatic b-cells undergo several morphofunctional adaptations that result in hyperinsulinaemia. Failure of b-cells to compensate for this situation favours glucose homeostasis disruption, which can result in hyperglycaemia, particularly in susceptible individuals. GC treatment does not only alter pancreatic b-cell function but also affect them by their actions that can lead to hyperglucagonaemia, further contributing to glucose homeostasis imbalance and hyperglycaemia. In addition, the release of other islet hormones, such as somatostatin, amylin and ghrelin, is also affected by GC administration. These undesired GC actions merit further consideration for the design of improved GC therapies without diabetogenic effects. In summary, in this review, we consider the implication of GC treatment on peripheral IR, islet function and glucose homeostasis.

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Section: Cellular Mechanisms Of Gc Actionmentioning

confidence: 99%

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

Rafacho¹,

Ortsäter²,

Nadal³

et al. 2014

Journal of Endocrinology

184

114

View full text Add to dashboard Cite

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“…It is well known that 11β-hydroxysteroid dehydrogenase (11β-HSD) isoenzymes reversibly catalyze the interconversion between cortisol and cortisone. Endogenous cortisol is reversibly converted to its inactive metabolite, cortisone by 11β-HSD type 1 (3). On the contrary, 11β-HSD type 2 predominantly catalyzes the conversion of cortisol to cortisone mostly in mineralocorticoid target tissues (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous quantitative analysis of salivary cortisol and cortisone in Korean adults using LC-MS/MS

Lee¹,

Kwon

Shin

et al. 2010

BMB Reports

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The levels of salivary cortisol and cortisone in Korean adults were measured for the first time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The salivary cortisol and cortisone were separated within 10 min. The regression coefficients (r) of the calibration curves were greater than 0.999 for the two steroids. The limits of quantitation (LOQ) were 0.2 ng/ml for cortisol and 1 ng/ml for cortisone. The intra-day precisions of the assay were ＜3.9% and 8.6% for cortisol and cortisone respectively, and the inter-day precisions were ＜1.9% and 4.3% for cortisol and cortisone, respectively. The salivary cortisone concentrations were approximately 4-9 times higher than those of salivary cortisol during the daytime. Diurnal rhythms, during which the cortisol and cortisone concentrations were higher in the morning than in the afternoon, were also observed. The present assay may be useful for the diagnosis of several adrenal dysfunctions in clinical biochemistry. [BMB reports 2010; 43(7): 506-511]

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“…Mice homozygous for a targeted disruption of the 11␤-HSD1 gene cannot reduce 11-keto glucocorticoids to active 11-hydroxy steroids (12). Hepatic 11␤-HSD1 is the major site of regeneration of active glucocorticoids; in humans, inert cortisone administered orally is rapidly converted to cortisol, predominantly by the liver (13). As well as contributing toward plasma glucocorticoid levels, 11␤-HSD1 increases intracellular glucocorticoid levels, amplifying glucocorticoid action.…”

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confidence: 99%

C/EBP Regulates Hepatic Transcription of 11β-Hydroxysteroid Dehydrogenase Type 1

Williams¹,

Lyons²,

Macleod³

et al. 2000

Journal of Biological Chemistry

104

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Glucocorticoid action within individual cells is potently modulated by 11␤-hydroxysteroid dehydrogenase (11␤-HSD), which, by interconverting active and inert glucocorticoids, determines steroid access to receptors. Type 1 11␤-HSD (11␤-HSD1) is highly expressed in liver where it regenerates glucocorticoids, thus amplifying their action and contributing to induction of glucocorticoid-responsive genes, most of which are also regulated by members of the C/EBP (CAAT/enhancer-binding protein) family of transcription factors. Here we demonstrate that C/EBP␣ is a potent activator of the 11␤-HSD1 gene in hepatoma cells and that mice deficient in C/EBP␣ have reduced hepatic 11␤-HSD1 expression. In contrast, C/EBP␤ is a relatively weak activator of 11␤-HSD1 transcription in hepatoma cells and attenuates C/EBP␣ induction, and mice that lack C/EBP␤ have increased hepatic 11␤-HSD1 mRNA. The 11␤-HSD1 promoter (between ؊812 and ؉76) contains 10 C/EBP binding sites, and mutation of the promoter proximal sites decreases the C/EBP inducibility of the promoter. One site encompasses the transcription start, and both C/EBP␣ and C/EBP␤ are present in complexes formed by liver nuclear proteins at this site. The regulation of 11␤-HSD1 expression, and hence intracellular glucocorticoid levels, by members of the C/EBP family provides a novel mechanism for cross-talk between the C/EBP family of transcription factors and the glucocorticoid signaling pathway.Glucocorticoids, synthesized and secreted by the adrenal cortex, play a vital role in maintaining homeostasis, particularly during stress. The control of energy metabolism is central to the maintenance of homeostasis, and glucocorticoids play an important role in regulating glucose availability and utilization. In addition, during inflammation or injury, glucocorticoids potently suppress the immune response and play a role in the acute phase response in liver (1). The actions of glucocorticoids are principally mediated by the type II or glucocorticoid receptor and, in a limited number of tissues, by the related type I or mineralocorticoid receptor. The interaction between glucocorticoid hormone and receptors is crucially modulated by the glucocorticoid-metabolizing 11␤-hydroxysteroid dehydrogenase (11␤-HSD; EC 1.1

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Mineralocorticoid excess and inhibition of 11 β‐hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome

Cited by 181 publications

References 40 publications

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

Simultaneous quantitative analysis of salivary cortisol and cortisone in Korean adults using LC-MS/MS

C/EBP Regulates Hepatic Transcription of 11β-Hydroxysteroid Dehydrogenase Type 1

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