Dehydroepiandrosterone inhibits the amplification of glucocorticoid action in adipose tissue

Apostolova, Galina; Schweizer, Roberto A.S.; Balázs, Zoltán; Kostadinova, Radina; Odermatt, Alex

doi:10.1152/ajpendo.00442.2004

Cited by 84 publications

(84 citation statements)

References 63 publications

(70 reference statements)

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“…DHEA significantly lowered 11␤-HSD1 mRNA expression in liver (19 Ϯ 3% of control; P Ͻ 0.001), WAT (28 Ϯ 5%; P Ͻ 0.001), and kidney (57 Ϯ 10%; P Ͻ 0.01; Figure 4), in line with previous observations in C57BL/6J mice. 17 DHEA treatment for a relatively short time (12 d) did not significantly alter food intake or body weight in C57BL/6J mice and Sprague-Dawley rats (data not shown). Figure 2.…”

Section: Dhea Modulates Glucocorticoid Metabolism By Inducing a Switcmentioning

confidence: 91%

“…17 Here, we tested the hypothesis that DHEA has antiglucocorticoid effects by inducing a switch from 11␤-HSD1-dependent activation to 11␤-HSD2-dependent inactivation of glucocorticoids. We investigated the impact of DHEA on 11␤-HSD2 expression and activity in RCCD2 rat cortical collecting duct cells.…”

Section: Dhea Upregulates 11␤-hsd2 Expression and Activity In Renal Cmentioning

confidence: 99%

“…To ensure that the DHEA-mediated suppression of glucocorticoid reactivation reported in a previous study with mice 17 is not species specific, we measured 11␤-HSD1 mRNA expression in liver, white adipose tissue (WAT), and kidney from Sprague-Dawley rats fed standard rodent chow or chow containing 0.2% DHEA. DHEA significantly lowered 11␤-HSD1 mRNA expression in liver (19 Ϯ 3% of control; P Ͻ 0.001), WAT (28 Ϯ 5%; P Ͻ 0.001), and kidney (57 Ϯ 10%; P Ͻ 0.01; Figure 4), in line with previous observations in C57BL/6J mice.…”

Section: Dhea Modulates Glucocorticoid Metabolism By Inducing a Switcmentioning

confidence: 99%

“…16 We recently reported reduced 11␤-HSD1 expression in response to DHEA in 3T3-L1 adipocytes and in liver and adipose tissue of treated mice. 17 We showed that the CCAAT/enhancer-binding protein (C/EBP) family of basic leucin zipper transcription factors C/EBP-␣, C/EBP-␤, and C/EBP-␦ is involved in the DHEA-mediated regulation of 11␤-HSD1 expression. C/EBP can act as transcriptional activators as well as repressors.…”

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DHEA Induces 11β-HSD2 by Acting on CCAAT/Enhancer-Binding Proteins

Balázs

Schweizer²,

Frey³

et al. 2008

Journal of the American Society of Nephrology

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11␤-Hydroxysteroid dehydrogenase (11␤-HSD) type 1 and type 2 catalyze the interconversion of inactive and active glucocorticoids. Impaired regulation of these enzymes has been associated with obesity, diabetes, hypertension, and cardiovascular disease. Previous studies in animals and humans suggested that dehydroepiandrosterone (DHEA) has antiglucocorticoid effects, but the underlying mechanisms are unknown. In this study, DHEA treatment markedly increased mRNA expression and activity of 11␤-HSD2 in a rat cortical collecting duct cell line and in kidneys of C57BL/6J mice and Sprague-Dawley rats. DHEA-treated rats tended to have reduced urinary corticosterone to 11-dehydrocorticosterone ratios. It was found that CCAAT/enhancer-binding protein-␣ (C/EBP-␣) and C/EBP-␤ regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11␤-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing C/EBP-␤ mRNA and protein expression. Moreover, it is shown that C/EBP-␣ and C/EBP-␤ differentially regulate the expression of 11␤-HSD1 and 11␤-HSD2. In conclusion, DHEA induces a shift from 11␤-HSD1 to 11␤-HSD2 expression, increasing conversion from active to inactive glucocorticoids. This provides a possible explanation for the antiglucocorticoid effects of DHEA. Enhanced glucocorticoid effects, mainly as a result of locally disturbed glucocorticoid metabolism, contribute to diseases such as hypertension and the metabolic syndrome. 1-3 The adrenal steroid hormone precursor dehydroepiandrosterone (DHEA) is the most abundant circulating steroid in humans, with peak levels between 20 and 30 yr of age, followed by a steady, age-dependent decline. Many metabolic effects, including antiobesity, antidiabetic, and antiaging properties, have been attributed to DHEA. 4 In rodents, DHEA attenuated ischemia/reperfusion-induced oxidative stress and renal dysfunction, 5 showed beneficial effects in diabetic nephropathy, 6,7 and inhibited the age-related development of proteinuria. 8 DHEA seems to counteract several adverse effects of excessive glucocorticoid action, including a negative correlation between DHEA concentrations and body mass index, visceral adiposity, and impaired insulin sensitivity in elderly individuals 9 ; however, the molecular mechanisms underlying these antiglucocorticoid effects remain unclear.In peripheral tissues, local glucocorticoid metabolism is mainly controlled by 11␤-hydroxysteroid dehydrogenase (11␤-HSD1) and 11␤-HSD2. 11␤-HSD1 catalyzes the reduction of inactive 11-ketoglucocorticoids (cortisone, 11-dehydrocorticosterone) into active 11␤-hy-

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Section: Dhea Modulates Glucocorticoid Metabolism By Inducing a Switcmentioning

confidence: 91%

Section: Dhea Upregulates 11␤-hsd2 Expression and Activity In Renal Cmentioning

confidence: 99%

Section: Dhea Modulates Glucocorticoid Metabolism By Inducing a Switcmentioning

confidence: 99%

mentioning

confidence: 99%

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DHEA Induces 11β-HSD2 by Acting on CCAAT/Enhancer-Binding Proteins

Balázs

Schweizer²,

Frey³

et al. 2008

Journal of the American Society of Nephrology

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“…It also has properties to increase insulin sensitivity in hepatocytes (25). In addition, it has been shown that DHEA can inhibit 11β-hydroxysteroid dehydrogenase 1 expression in liver and adipose tissues (26). It is proposed that the overexpression of 11β-hydroxysteroid dehydrogenase 1 in adipose tissues increases the local cortisol production and thereby leads to the metabolic syndrome-like status (27,28).…”

Section: Discussionmentioning

confidence: 99%

Serum Dehydroepiandrosterone Sulphate Levels in Patients with Non-Alcoholic Fatty Liver Disease

et al. 2011

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Backgound Dehydroepiandrosterone (DHEA) is an adrenal hormone reported to prevent body weight gain, diabetes mellitus and atherosclerosis. We hypothesized that DHEA is involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD) often associated with obesity and insulin resistance. In this study, we aimed to examine the clinical significance of serum DHEA sulfate (DHEAS) in patients with NAFLD. Methods We determined serum DHEAS, serum alanine aminotransferase (ALT), serum lipids, plasma fasting glucose and insulin levels in 158 Japanese men who had neither viral hepatic diseases nor alcohol intake exceeding 20 g/day. NAFLD was diagnosed by the presence of fatty change of the liver by echotomographic examination. Results Among the study subjects, 69 were diagnosed as having NAFLD. Their serum DHEAS levels were significantly higher than in 89 subjects without NAFLD. Serum DHEAS levels in 19 NAFLD patients with elevated ALT levels (>40 U/L) were significantly higher than in the other 50 NAFLD patients with normal ALT levels (!40 U/L). Multivariate regression analysis demonstrated that serum ALT was positively correlated with serum DHEAS, serum triglyceride and body mass index. Conclusion Serum DHEAS levels are increased in patients with NAFLD with elevated ALT levels. Increased serum DHEAS may be a component of the pathophysiology of NAFLD.

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Corticosterone and dehydroepiandrosterone have opposing effects on adult neuroplasticity in the avian song control system

Newman

MacDougall‐Shackleton

et al. 2010

J of Comparative Neurology

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Chronic elevations in glucocorticoids can decrease the production and survival of new cells in the adult brain. In rat hippocampus, supraphysiological doses of dehydroepiandrosterone (DHEA; a sex steroid precursor synthesized in the gonads, adrenals, and brain) have antiglucocorticoid properties. With male song sparrows (Melospiza melodia), we examined the effects of physiological doses of corticosterone, the primary circulating glucocorticoid in birds, and DHEA on adult neuroplasticity. We treated four groups of nonbreeding sparrows for 28 days with empty (control), corticosterone, DHEA, or corticosterone + DHEA implants. Subjects were injected with BrdU on days 3 and 4. In HVC, a critical song control nucleus, corticosterone and DHEA had independent, additive effects. Corticosterone decreased, whereas DHEA increased, HVC volume, NeuN(+) cell number, and BrdU(+) cell number. Coadministration of DHEA completely reversed the neurodegenerative effects of chronic corticosterone treatment. In an efferent target of HVC, the robust nucleus of the arcopallium (RA), DHEA increased RA volume, but this effect was blocked by coadministration of corticosterone. There were similar antagonistic interactions between corticosterone and DHEA on BrdU(+) cell number in the hippocampus and ventricular zone. This is the first report on the effects of corticosterone treatment on the adult song control circuit, and HVC was the most corticosterone-sensitive song nucleus examined. In HVC, DHEA is neuroprotective and counteracts several pronounced effects of corticosterone. Within brain regions that are particularly vulnerable to corticosterone, such as the songbird HVC and rat hippocampus, DHEA appears to be a potent native antiglucocorticoid.

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Dehydroepiandrosterone inhibits the amplification of glucocorticoid action in adipose tissue

Cited by 84 publications

References 63 publications

DHEA Induces 11β-HSD2 by Acting on CCAAT/Enhancer-Binding Proteins

DHEA Induces 11β-HSD2 by Acting on CCAAT/Enhancer-Binding Proteins

Serum Dehydroepiandrosterone Sulphate Levels in Patients with Non-Alcoholic Fatty Liver Disease

Corticosterone and dehydroepiandrosterone have opposing effects on adult neuroplasticity in the avian song control system

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