11β-hydroxysteroid dehydrogenase 1 in adipocytes: Expression is differentiation-dependent and hormonally regulated

Napolitano, A; Voice, Michael W.; Edwards, C. R. W.; Seckl, Jonathan R.; Chapman, Karen

doi:10.1016/s0960-0760(97)00200-8

Cited by 113 publications

(76 citation statements)

References 42 publications

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“…In accordance with the previous observations (Napolitano et al 1998), a little (lower than 2%) cortisone to cortisol conversion was measured in undifferentiated 3-T3-L1 cells. Differentiation was accompanied by a severalfold elevation of the reductase activity, reaching a peak value at the seventh day (Fig.…”

Section: Cortisone Reductase Activity Increases In Admscs and 3t3-l1 supporting

confidence: 92%

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

Senesi

Marcolongo

Manini

et al. 2008

Journal of Molecular Endocrinology

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The reductase activity of 11b-hydroxysteroid dehydrogenase type 1 (HSD11B1) plays an important role in the growth and differentiation of adipose tissue via the prereceptorial activation of glucocorticoids. This enzyme colocalizes with hexose-6-phosphate dehydrogenase (H6PD) at the luminal surface of the endoplasmic reticulum membrane, and the latter enzyme provides NADPH to the former, which can thus act as an 11b-reductase. It was suggested that, during adipogenesis, the increased expression of H6PD causes a dehydrogenase-to-reductase switch in the activity of HSD11B1. However, only the expression of the HSD11B1 has been extensively studied, and little is known about the expression of H6PD. Here, we investigated the expression and the activity of H6PD in the course of the differentiation of human adipose-derived mesenchymal stem cells (ADMSCs) and murine 3T3-L1 cells. It was found that H6PD is already present in adipose-derived stem cells and in 3T3-L1 fibroblasts even before the induction of adipogenesis. Moreover, mRNA and protein levels, as well as the microsomal H6PD activities remained unchanged during the differentiation. At the same time a great induction of HSD11B1 was observed in both cell types. The observed constant expression of H6PD suggests that HSD11B1 acts as a reductase throughout the adipogenesis process in human ADMSCs and murine 3T3-L1 cells.

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Section: Cortisone Reductase Activity Increases In Admscs and 3t3-l1 supporting

confidence: 92%

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

Senesi

Marcolongo

Manini

et al. 2008

Journal of Molecular Endocrinology

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“…Under basal conditions in liver, the ratio of C/EBP␣ to C/EBP␤ will be high, favoring high levels of 11␤-HSD1 transcription and hence local production of active glucocorticoids. Treatments that decrease the ratio of C/EBP␣/C/EBP␤, for example glucagon (which increases intracellular cAMP) or glucocorticoid administration, would be predicted to decrease 11␤-HSD1 transcription, as found in some studies in vitro (16,44) and in vivo (23,45). In addition, C/EBP␤ is regulated both at the level of translation and post-translationally (reviewed in Refs.…”

Section: Discussionmentioning

confidence: 83%

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

Williams¹,

Lyons²,

Macleod³

et al. 2000

Journal of Biological Chemistry

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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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“…11 -HSD1 is expressed in mouse, rat (Napolitano et al, 1998) and in human adipose tissue (Bujalska et al, 1997, Morton and. 11 -HSD1 levels increase with differentiation of mature adipocytes (3T3F442A and 3T3-L1 cells) -and the reaction direction is exclusively 11-ketoreduction (Napolitano et al, 1998).…”

Section: -Hydroxysteroid Dehydrogenase Type 1 In Adipocytesmentioning

confidence: 99%

“…11 -HSD1 levels increase with differentiation of mature adipocytes (3T3F442A and 3T3-L1 cells) -and the reaction direction is exclusively 11-ketoreduction (Napolitano et al, 1998). Unlike the undifferentiated 3T3 cells, primary mouse preadipocytes express abundant 11 -HSD1 (De Sousa Peixoto et al, 2008).…”

Section: -Hydroxysteroid Dehydrogenase Type 1 In Adipocytesmentioning

confidence: 99%

Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

Morton

2010

Molecular and Cellular Endocrinology

150

159

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11β-hydroxysteroid dehydrogenase 1 in adipocytes: Expression is differentiation-dependent and hormonally regulated

Cited by 113 publications

References 42 publications

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

Constant expression of hexose-6-phosphate dehydrogenase during differentiation of human adipose-derived mesenchymal stem cells

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

Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

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