11β-Hydroxysteroid dehydrogenases of the choriocarcinoma cell line JEG-3 and their inhibition by glycyrrhetinic acid and other natural substances

Gómez-Sánchez, Elise P.; Cox, Diana L.; Foecking, Mark F.; Ganjam, Venkataseshu K.; Gómez-Sánchez, Celso E.

doi:10.1016/0039-128x(95)00201-z

Cited by 39 publications

(23 citation statements)

References 38 publications

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“…Two of the choriocharcinoma cell lines (BeWo and JEG) express GC receptor, whereas no detectable levels of GC receptor were identified in the JAR cells. Moreover, 11b-HSD-2 activity (Gomez- Sanchez et al 1996) and functional mineralocorticoid receptors (Listwak et al 1996) were identified in JEG-3 cells. JAR cells were used as negative control in this study to identify a potential involvement of the mineralocorticoid receptor in GC effects, because GCs can also transactivate this receptor (Grossmann et al 2004).…”

Section: Discussionmentioning

confidence: 97%

Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines

Mandl

Ghaffari-Tabrizi²,

Haas³

et al. 2006

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Several clinical situations require continuous glucocorticoid (GC) treatment during pregnancy. A well-known deleterious side effect of such treatment is the higher incidence of growth-restricted fetuses, for which a too shallow trophoblast invasion is presently hypothesised as the underlying cause. This study investigated whether the synthetic GC triamcinolone acetonide (TA) influences proliferation, invasion and endocrine activity of human trophoblast. BeWo and JEG-3 choriocarcinoma cell lines both express GC receptors (western blotting) and were used as models for human trophoblast. JAR devoid cells of GC receptor were used as negative control. The cells were cultured for 48 h without (control) or with 0.5, 5 and 50 mM TA. In the presence and absence of serum, proliferation was determined by cell counting and measuring the cell cycle regulating protein cyclin B1 (Western blotting); invasion was determined by a conventional Matrigel invasion assay and by measuring the secretion (ELISA) of matrix-metalloproteinases (MMP-2, MMP-9) into the culture medium; endocrine activity was assessed by measuring the levels of human chorionic gonadotropin (ELISA) into the culture medium. TA altered the number of viable and dead cells as well as cyclin B1 levels and, to a lesser extent, invasion of BeWo and JEG-3, with a strong influence of serum. BeWo and JEG-3 cells reacted differently and in most instances reverse. In the cell lines used as models of human trophoblast, TA alter some functions relevant to proliferation and invasion, and suggest that caution should be exercised when treating women with GCs during pregnancy.

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Section: Discussionmentioning

confidence: 97%

Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines

Mandl

Ghaffari-Tabrizi²,

Haas³

et al. 2006

Reproduction

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“…In addition to the identification of additional 11P-HSD isozymes (1 ID-HSD-3 has been suggested recently in the JEG-3 cell line [20]) and polymorphism studies, an exciting series of results can be expected once the molecular regulation of 11P-HSD-1 has been determined, selective inhibitors or inducers developed, or transgenic animals lacking 11P-HSD-I [21] used to study the significance of 1 ID-HSD-I in detoxification processes in vivo.…”

Section: Discussionmentioning

confidence: 99%

The 11β‐Hydroxysteroid Dehydrogenase System, A Determinant of Glucocorticoid and Mineralocorticoid Action

Uct.

Persson

Jörnvall

1997

European Journal of Biochemistry

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processesCarbonyl reduction is a significant step in the biotransformation leading to the elimination, of endogenous and exogenous aldehydes, ketones and quinones. This reaction is mediated by members of the aldoketo reductase and short-chain dehydrogenaseheductase (SDR) superfamilies. The essential role of these enzymes in protecting organisms from damage by the accumulation of toxic carbonyl compounds is generally accepted, although their physiological roles are not always clear. Recently, the SDR enzyme 1 1P-hydroxysteroid dehydrogenase-I has been identified to perform an important role in the detoxification of non-steroidal carbonyl compounds, in addition to metabolising its physiological glucocorticoid substrates. This review summarises the current knowledge of type-1 1 1P-hydroxysteroid dehydrogenase and discusses possible substratehnhibitor interactions. They might impair either the physiological function of glucocorticoids or the detoxification of non-steroid carbonyl compounds.Keywords: aldehyde ; ketone and quinone detoxification ; nicotine-derived nitrosamine ketone, carbonyl reduction; reductive metabolism; 1 I@-hydroxysteroid dehydrogenase ; short-chain dehydrogenasekeductase ; steroid metabolism ; microsomal reductase ; xenobiotic metabolism.Over the last decade 1 lp-hydroxysteroid dehydrogenases (1 1P-HSD) have received increasing attention from the scientific community. These enzymes have a multitude of (patho)physiological functions and a wide tissue distribution of isoforms. The key role of their enzymatic activity is the metabolism of physiologically occurring glucocorticoids, i.e. the 1 1P-oxidoreduction of cortisol (corticosterone) and cortisone (dehydrocorticosterone).However, in 1993 it was discovered that hepatic 11P-HSD-1, in addition to its role in the metabolism of physiological steroid substrates, is also capable of catalysing the carbonyl reduction of non-steroid xenobiotic aldehydes, ketones and quinones [ 1,

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“…HPLC grade hexane, ethyl acetate, ethanol, chloroform and acetone were obtained from Fisher Scientific Co. (Pittsburgh, PA). [1,2,6, H]-DHEA and [1,2,6,7-3 H]-CS were purchased from NEN Life Science Products (Boston, MA). Tritiated 7α-OH-DHEA and 7-oxo-DHEA were prepared by the method developed by our laboratory [9].…”

Section: Methodsmentioning

confidence: 99%

“…The major role proposed for 11βHSD2 and 3 is to convert GC from their active alcohol form (cortisol and corticosterone) to the keto non-active form (cortisone and dehydrocorticosterone) in an irreversible reaction, thereby, preventing binding of GC to the mineralocorticoid receptor. 11βHSD activity has been observed in nuclei, mitochondrial and microsomal organelles from normal human and rat placenta [5] and choriocarcinoma cells [6]. In human kidney nuclei, immuno-reactive human 11βHSD2 accounted for 40% of total cellular 11βHSD2 protein content [7,8].…”

Section: Introductionmentioning

confidence: 99%

Interactions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: Nuclear and microsomal 11β-hydroxysteroid dehydrogenases

Robinzon

Prough

2005

Archives of Biochemistry and Biophysics

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The 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) activates glucocorticoids (GC) by reversibly converting 11-keto-GC to 11-hydroxy-GC, while 11βHSD2 and 11βHSD3 only catalyzes the reverse reaction. Recently, rat and human 11βHSDs were shown to interconvert 7α-and 7β-hydroxy-dehydroepiandrosterone (7α-or 7β-OH-DHEA) with 7-oxo-DHEA. We report that pig kidney microsomes (PKMc) and nuclei (PKN) oxidize 7α-OH-DHEA to 7-oxo-DHEA at higher rates with NAD + , than with NADP + . Corticosterone (CS), dehydrocoticosterone (DHC), 11α-and 11β-hydroxyprogesterone, and carbenoxolone completely inhibited these reactions, while 7-oxo-DHEA only inhibited the NAD + -dependent reaction. Conversely, CS oxidation was not inhibited by 7α-OH-DHEA or 7-oxo-DHEA. PKMc and PKN did not convert 7-oxo-DHEA to 7-OH-DHEA with either NADPH or NADH. Finally, PKN contained a high affinity, NADPH-dependent 11βHSD that reduces DHC to CS. The GC effects on interconversion of DHEA metabolites may have clinical significance, since DHEA and its 7-oxidized derivatives have been proposed for treatment of human autoimmune and inflammatory disorders.

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11β-Hydroxysteroid dehydrogenases of the choriocarcinoma cell line JEG-3 and their inhibition by glycyrrhetinic acid and other natural substances

Cited by 39 publications

References 38 publications

Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines

Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines

The 11β‐Hydroxysteroid Dehydrogenase System, A Determinant of Glucocorticoid and Mineralocorticoid Action

Interactions between dehydroepiandrosterone and glucocorticoid metabolism in pig kidney: Nuclear and microsomal 11β-hydroxysteroid dehydrogenases

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