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Jeroen C W Rijk, Toine F H Bovee, Ad A C M Peijnenburg, Maria J Groot, Ivonne M C M Rietjens, Michel W F Nielen
Biotransformation of inactive prohormones like dehydroepiandrosterone (DHEA) can lead to the formation of potent androgens and subsequent androgenic responses in target tissues. In the present study, precision-cut bovine liver slices were used to study the effects of DHEA on the metabolite, transcript and androgenic activity level. Bovine liver slices were exposed for 6h to various concentrations of DHEA. Changes in androgenic activity of the DHEA containing cell culture media were measured using a yeast androgen bioassay and metabolites were identified using ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS), while gene expression in the DHEA-treated liver slices was examined using bovine microarrays and compared with the profile as obtained with 17ß-testosterone (17ß-T)...
September 2012: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Russell Joseph Amato, Mary Worrel Hulin, Peter John Winsauer
Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectivity for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol-maintained and food-maintained responding, compared with the control, while also decreasing the blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding...
June 2012: Behavioural Pharmacology
Mary E Worrel, Olga V Gurkovskaya, Stuart T Leonard, Peter B Lewis, Peter J Winsauer
Administration of dehydroepiandrosterone (DHEA), a neurosteroid that can negatively modulate the GABA A receptor, has been shown to decrease voluntary intake of ethanol in rats. In vivo, DHEA can be metabolized to a variety of metabolites, including 3β-acetoxyandrost-5-ene-7,17-dione (7-keto DHEA), a metabolite without the prohormonal effects of DHEA. This study compared the effectiveness of 7-keto DHEA with DHEA for reducing ethanol intake in the same group of rats. The subjects, previously trained to drink ethanol using a saccharin-fading procedure, had access to ethanol for 30 min daily and the amount consumed was recorded...
June 2011: Alcohol
András Gergely, Péter Horváth, György Szász, Gábor Veress
A three-step gradient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the separation of dehydroepiandrosterone (DHEA), its sulfate ester (DHEA-S), its three C7-oxidized metabolites (7alphaOH-DHEA, 7betaOH-DHEA, 7-keto-DHEA), and its biosynthetic congeners (androstenedione, testosterone, estradiol, pregnenolone). This new method allows the quantitative characterization of DHEA metabolism and biosynthetic transformation under given physiological, pathological, or therapeutically influenced circumstances...
August 2009: Analytical and Bioanalytical Chemistry
Zoltán Balázs, Lyubomir G Nashev, Charlie Chandsawangbhuwana, Michael E Baker, Alex Odermatt
Intracellular glucocorticoid reactivation is catalyzed by 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1), which functions predominantly as a reductase in cells expressing hexose-6-phosphate dehydrogenase (H6PDH). We recently showed that the ratios of cortisone to cortisol and 7-keto- to 7-hydroxy-neurosteroids are regulated by 11beta-HSD1 and very much depend on coexpression with H6PDH, providing cosubstrate NADPH. Here, we investigated the impact of H6PDH on the modulation of 11beta-HSD1-dependent interconversion of cortisone and cortisol by inhibitors and alternative substrates...
March 25, 2009: Molecular and Cellular Endocrinology
Lyubomir G Nashev, Charlie Chandsawangbhuwana, Zoltan Balazs, Atanas G Atanasov, Bernhard Dick, Felix J Frey, Michael E Baker, Alex Odermatt
BACKGROUND: The role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in the regulation of energy metabolism and immune system by locally reactivating glucocorticoids has been extensively studied. Experiments determining initial rates of enzyme activity revealed that 11beta-HSD1 can catalyze both the reductase and the dehydrogenase reaction in cell lysates, whereas it predominantly catalyzes the reduction of cortisone to cortisol in intact cells that also express hexose-6-phosphate dehydrogenase (H6PDH), which provides cofactor NADPH...
2007: PloS One
Henry Lardy, Ashok Marwah, Padma Marwah
Dehydroepiandrosterone (DHEA), produced from cholesterol in the adrenals, is the most abundant steroid in our circulation. It is present almost entirely as the sulfate ester, but the free steroid is the form that serves as a precursor of estrogens and androgens, as well as 7- and 16-oxygenated derivatives. Mammalian tissues reduce the 17-keto Group of DHEA to produce androstenediol-a weak estrogen and full-fledged androgen. Its androgen activity is not inhibited by the anti-androgens commonly used to treat prostate cancer...
2005: Vitamins and Hormones
Frans T Delbeke, Peter Van Eenoo, Wim Van Thuyne, Noël Desmet
Several precursors of testosterone and nandrolone introduced on the nutritional supplement market as performance enhancing drugs are banned in sports. Until now they are legally sold without a prescription in the US. Results of excretion studies with related compounds including 7-keto-DHEA and 1-androstenediol are presented. The main metabolites of 7-keto-DHEA are 7-hydroxylated compounds. The commercial 1-androstenediol preparation was contaminated with several other anabolic steroids. Oxidation of 1-androstenediol to 1-androstenedione seems to be the major renal metabolic pathway...
December 2002: Journal of Steroid Biochemistry and Molecular Biology
Garret Ihler, Hasna Chami-Stemmann
Patients with Raynaud's phenomenon have abnormal digital vasoconstriction in response to cold. The pathogenesis remains unknown but may involve a local neurovascular defect leading to vasoconstriction. Diagnosis of primary Raynaud's phenomenon is based on typical symptomatology coupled with normal physical examination, normal laboratory studies and lack of observable pathology by nail fold capillaroscopy. Secondary Raynaud's phenomenon is known to occur associated with several connective tissue diseases, vascular injury due to repeated vibrational trauma, and other causes which produce demonstrable vascular and microcirculatory damage...
March 2003: Medical Hypotheses
N P Gontscharow, A J Simarina, S K Jefremova, R Schön, K Schubert
The adrenal steroid secretion was investigated in male baboons (Papio hamadryas) treated for a long time with sodium chloride, in comparison to an untreated control group. In animals treated with NaCl, the secretion of progesterone, 17alpha-hydroxyprogesterone, 11-deoxycortisol, aldosterone and corticosterone was decreased, while cortisone, pregnenolone, 7-keto-cholesterol, 7-keto-DHEA, DHEA and adrenosterone were increased.
January 1975: Endokrinologie
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