7-케토 DHEA
7-Keto DHEA
📚 관련 논문 (28편)
1. Arch Gynecol Obstet. 2023 Sep;308(3):777-785. doi: 10.1007/s00404-022-06884-8. Epub 2022 Dec 25. A systematic review of the impact of 7-keto-DHEA on body weight. Jeyaprakash N(1), Maeder S(1), Janka H(2), Stute P(3)(4). Author information: (1)Department of Obstetrics and Gynecology, Universit
1. J Nutr Biochem. 2007 Sep;18(9):629-34. doi: 10.1016/j.jnutbio.2006.11.008. Epub 2007 Apr 5. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. Zenk JL(1), Frestedt JL, Kuskowski MA. Author information: (1)Department of Clinical Affairs, Minnesota Applied Research Center, Edina, MN 55435, USA. john@zenk.net This study tested the hypothesis that 3-acetyl-7-oxo-dehydroepiandrosterone alone (7-Keto) and in combination with calcium citrate, green tea extract, ascorbic acid, chromium nicotinate and cholecalciferol (HUM5007) will increase the resting metabolic rate (RMR) of overweight subjects maintained on a calorie-restricted diet. In this randomized, double-blind, placebo-controlled, crossover trial, overweight adults on a calorie-restricted diet were randomized to three 7-day treatment periods with 7-Keto, HUM5007 or placebo. Resting metabolic rate was measured by indirect calorimetry at the beginning and end of each treatment period with a 7-day washout between testing periods. Of 45 subjects enrolled, 40 completed the study (30 women, 10 men; mean age, 38.5 years; mean mass index, 32.0 kg/m(2)). During the placebo treatment, RMR decreased by 3.9% (75+/-111 kcal/day; mean+/-S.D.); however, RMR increased significantly by 1.4% (21+/-115 kcal/day) and 3.4% (59+/-118 kcal/day) during the 7-Keto and HUM5007 treatment periods, respectively (each compared to placebo, P=.001). No significant differences were found between the treatment periods with respect to compliance or adverse events. In this study, the administration of HUM5007 or 7-Keto reversed the decrease in RMR normally associated with dieting. HUM5007 and 7-Keto increased RMR above basal levels and may benefit obese individuals with impaired energy expenditure. HUM5007 and 7-Keto were generally well tolerated and no serious adverse events were reported. DOI: 10.1016/j.jnutbio.2006.11.008 PMID: 17418559 [Indexed for MEDLINE]
1. Drug Test Anal. 2019 Nov;11(11-12):1629-1643. doi: 10.1002/dta.2734. Epub 2019 Dec 13. 7-keto-DHEAmetabolism in humans. Pitfalls in interpreting the analytical results in the antidoping field. Martinez-Brito D(1), de la Torre X(1), Colamonici C(1), Curcio D(1), Botrè F(1)(2). Author information: (1)Laboratorio Antidoping FMSI, Rome, Italy. (2)Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy. 7-keto-DHEA (3β-hydroxy-androst-5-ene-7,17-dione) is included in section S1 of the World Antidoping Agency (WADA) List of Prohibited Substances. The detection of its misuse in sports needs special attention, since it is naturally present in urine samples. The main goal of this study is to investigate the in vivo metabolism of 7-keto-DHEA after a single administration to healthy volunteers and to better describe the relationship between arimistane (androst-5-ene-7,17-dione) and 7-keto-DHEA after the application of the common routine procedures to detect anabolic steroids in WADA accredited antidoping laboratories. Free, glucuro-, and sulpho-conjugated steroids extracted from urine samples obtained before and after the administration of 7-keto-DHEA were analyzed by different gas chromatographic (GC)-mass spectrometric (MS) techniques. Gas chromatography coupled to tandem MS to study the effect on the endogenous steroid profile, coupled to isotope ratio mass spectrometry (IRMS) to investigate the potential formation of androgens derived from DHEA and coupled to high resolution accurate mass spectrometry (HRMS) to investigate new diagnostic metabolites. The analysis by IRMS confirmed that there is no formation of DHEA from 7-keto-DHEA. Ten proposed metabolites, not previously reported, were described. These include reduced and hydroxylated structures that are not considered part of the steroid profile in antidoping analyses. They showed considerable responses in all fractions analyzed. Some deoxidation reactions (including arimistane formation) were found and most probably can be linked to the sample preparation or instrumental analysis. This is important when interpreting the results after the application of procedures to detect steroids in urine currently used in antidoping laboratories. 7-keto-DHEA metabolism in humans for antidoping purposes was studied and unexpected results were found. This could lead to a misinterpretation of the data, depending on the procedure applied and the analytical instrumentation used. © 2019 John Wiley & Sons, Ltd. DOI: 10.1002/dta.2734 PMID: 31701664 [Indexed for MEDLINE]
2. Steroids. 2018 Dec;140:185-195. doi: 10.1016/j.steroids.2018.10.010. Epub 2018 Nov 3. Chemical synthesis of 7-oxygenated 12α-hydroxy steroid derivatives to enable the biochemical characterization of cytochrome P450 8B1, the oxysterol 12α-hydroxylase enzyme implicated in cardiovascular health and obesity. Offei SD(1), Arman HD(1), Baig MO(2), Chavez LS(2), Paladini CA(2), Yoshimoto FK(3). Author information: (1)Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249-0698, United States. (2)Department of Biology, UTSA Neurosciences Institute, The University of Texas at San Antonio, San Antonio, TX 78249-0698, United States. (3)Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249-0698, United States. Electronic address: francis.yoshimoto@utsa.edu. Cholic acid is the endogenous 12α-hydroxylated bile acid, which possesses enhanced cholesterol absorption properties compared to its 12-desoxy counterpart, chenodeoxycholic acid. The oxysterol 12α-hydroxylase enzyme is cytochrome P450 8B1 (P450 8B1), which regioselectively and stereoselectively incorporates the 12α-hydroxy group in 7α-hydroxycholest-4-en-3-one, the biosynthetic precursor of cholic acid. Despite the vital role of P450 8B1 activity in cardiovascular health, research studies of other 12α-hydroxy steroid derivatives are rare. A synthetic route to incorporate a C12α-hydroxy group into the C12-methylene (-CH2-) in dehydroepiandrosterone derivatives is disclosed. The incorporation of the C12-oxygen was accomplished through a copper mediated Schönecker oxidation of an imino-pyridine intermediate, introducing the 12β-hydroxy group. The resulting 12β-hydroxy steroid derivative was oxidized to the C12-ketone, which was stereoselectively reduced with lithium tri-sec-butylborohydride to afford the 12α-hydroxy stereochemistry. The C7-position was oxidized to yield the various 7-keto, 7β-hydroxy, and 7α-hydroxy derivatives. Furthermore, 7-ketodehydroepiandrosterone and 12 α-hydroxy-7-ketodehydroepiandrosterone both displayed NMDA receptor antagonistic activities at 10 μM concentrations. These C12α-hydroxy steroids will be used as tools to identify new biochemical properties of the enzymatic products of P450 8B1, the oxysterol 12α-hydroxylase. Copyright © 2018 Elsevier Inc. All rights reserved. DOI: 10.1016/j.steroids.2018.10.010 PMCID: PMC6249089 PMID: 30399365 [Indexed for MEDLINE]
3. Steroids. 2015 Sep;101:103-9. doi: 10.1016/j.steroids.2015.06.005. Epub 2015 Jun 16. Allylic oxidation of steroidal olefins by vanadyl acetylacetonate and tert-butyl hydroperoxide. Grainger WS(1), Parish EJ(2). Author information: (1)Department of Chemistry and Biochemistry, College of Science and Mathematics, Auburn University, Auburn, AL 36849-5319, United States. (2)Department of Chemistry and Biochemistry, College of Science and Mathematics, Auburn University, Auburn, AL 36849-5319, United States. Electronic address: parisej@auburn.edu. Readily available vanadyl acetylacetonate was found to oxidize the allylic sites of Δ(5) steroidal alcohols without protection of hydroxyl groups. Cholesterol, dehydroepiandrosterone, cholesterol benzoate, cholesterol acetate, pregnenolone, and 5-pregnen-3,20-diene were oxidized to 7-keto products using vanadyl acetylacetonate in one pot reactions at room temperature in the presence of oxygen and water. Copyright © 2015 Elsevier Inc. All rights reserved. DOI: 10.1016/j.steroids.2015.06.005 PMID: 26091580 [Indexed for MEDLINE]
4. Toxicol In Vitro. 2012 Sep;26(6):1014-21. doi: 10.1016/j.tiv.2012.04.012. Epub 2012 May 26. Bovine liver slices: A multifunctional in vitro model to study the prohormone dehydroepiandrosterone (DHEA). Rijk JC(1), Bovee TF, Peijnenburg AA, Groot MJ, Rietjens IM, Nielen MW. Author information: (1)RIKILT - Institute of Food Safety, Wageningen UR. P.O. Box 230, 6700 AE Wageningen, The Netherlands. jeroen.rijk@wur.nl 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). An increase in androgenic activity was observed in the bioassay upon testing of samples from incubations of DHEA with liver slices and the formation of 4-androstenedione (4-AD), 5-androstene-3ß,17ß-diol, 17ß-T, 7α-hydroxy-DHEA, 7-keto-DHEA and 17α-T could be confirmed by UPLC-TOFMS analysis. Exposure of liver slices to DHEA and the strong androgen 17ß-T resulted in the identification of significantly up- and down-regulated genes and revealed similar gene expression profiles for both compounds. The results indicate that DHEA itself is biologically not very active, but is rapidly converted by the liver slices into the more androgen active compounds 4-AD and 17ß-T. Moreover, the present data highlight the multi-functionality of bovine liver slices as an in vitro bioactivation model, allowing the assessment of androgen activity or gene expression as effect-based endpoints for prohormone exposure. Copyright © 2012 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.tiv.2012.04.012 PMID: 22640920 [Indexed for MEDLINE]
5. Behav Pharmacol. 2012 Jun;23(3):250-61. doi: 10.1097/FBP.0b013e32835342d2. A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule. Amato RJ(1), Hulin MW, Winsauer PJ. Author information: (1)Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, USA. Russell.j.amato@vanderbilt.edu 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. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared with food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, whereas it did not affect ethanol-maintained responding compared with the control. Low to intermediate doses of rauwolscine produced small, nonsignificant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence. DOI: 10.1097/FBP.0b013e32835342d2 PMCID: PMC3360959 PMID: 22473025 [Indexed for MEDLINE]
6. Alcohol. 2011 Jun;45(4):349-54. doi: 10.1016/j.alcohol.2010.08.020. Epub 2010 Nov 4. Effects of 7-keto dehydroepiandrosterone on voluntary ethanol intake in male rats. Worrel ME(1), Gurkovskaya OV, Leonard ST, Lewis PB, Winsauer PJ. Author information: (1)Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. 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. Subjects were administered 10 and 56 mg/kg of DHEA or 7-keto DHEA intraperitoneally 15 min before drinking sessions. Subjects received each particular dose daily until one of two criteria was met, that is, either ethanol intake did not differ by more than 20% of the mean for 3 consecutive days or for a maximum of 8 days. Both 10 and 56 mg/kg of 7-keto DHEA significantly reduced the dose of ethanol consumed. Although 10mg/kg of 7-keto DHEA produced decreases similar to those found with DHEA, the 56-mg/kg dose of 7-keto DHEA was significantly more effective at decreasing the dose of ethanol consumed than the same dose of DHEA. These results show that 7-keto DHEA is comparable with, or possibly more effective than, DHEA at decreasing ethanol consumption in rats, and that 7-keto DHEA is a compound deserving further investigation as a possible clinical treatment for alcohol abuse without the prohormonal effects of DHEA. Copyright © 2011 Elsevier Inc. All rights reserved. DOI: 10.1016/j.alcohol.2010.08.020 PMCID: PMC3095668 PMID: 21051179 [Indexed for MEDLINE]
7. Int J Pharm Compd. 2010 Nov-Dec;14(6):465-71. The clinical use of dehydroepiandrosterone in postmenopausal women. Bramwell BL(1). Author information: (1)Walgreens, West Plains, Missouri. A basic understanding of the distinct metabolism, mechanism of action, and clinical use of dehydroepiandrosterone and its metabolites is critical to balancing the hormone milieu in postmenopausal women. To date, studies of dehydroepiandrosterone therapy in women with adrenal insufficiency suggest that they are the most likely group to gain health benefits from dehydroepiandrosterone replacement therapy. Our understanding of the potential long-term health benefits of replacing dehydroepiandrosterone along with other deficient hormones is still only in its infancy. With the evidence currently available, however, one can reasonably suggest that dehydroepiandrosterone offers the promise of a safe and efficient replacement therapy for specific symptoms common to postmenopausal women. This article reviews the metabolism, physiology, and clinical use of dehydroepiandrosterone in postmenopausal women. The clinical effectiveness of dehydroepiandrosterone for vulvovaginal atrophy, sexual dysfunction, osteoporosis, adrenal and immunological function, cardiovascular disease, and, in combination, hormone replacement therapy is reviewed. In addition, the use of the dehydroepiandrosterone metabolite 7-keto-dehydroepiandrosterone for weight loss is discussed. PMID: 23965649
8. Anal Bioanal Chem. 2009 Aug;394(8):2105-9. doi: 10.1007/s00216-009-2917-3. Epub 2009 Jul 4. Gradient HPLC separation of dehydroepiandrosterone (DHEA) from its metabolites and biological congeners: role of tetrahydrofuran in the chromatographic mechanism. Gergely A(1), Horváth P, Szász G, Veress G. Author information: (1)Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes Endre u. 9, Budapest 1092, Hungary. 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. Tetrahydrofuran probably acts as a proton acceptor coadsorbent, while isopropanol behaves as a proton donor during the separation of testosterone, estradiol, and the stereoisomers of 7-OH-DHEA. DOI: 10.1007/s00216-009-2917-3 PMID: 19578835 [Indexed for MEDLINE]
9. Mol Cell Endocrinol. 2009 Mar 25;301(1-2):117-22. doi: 10.1016/j.mce.2008.10.021. Epub 2008 Oct 25. Hexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11beta-hydroxysteroid dehydrogenase 1. Balázs Z(1), Nashev LG, Chandsawangbhuwana C, Baker ME, Odermatt A. Author information: (1)Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. 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. Using HEK-293 cells expressing 11beta-HSD1 or coexpressing 11beta-HSD1 and H6PDH, we observed significant differences of 11beta-HSD1 inhibition by natural and pharmaceutical compounds as well as endogenous hormone metabolites. Furthermore, we show potent and dose-dependent inhibition of 11beta-HSD1 by 7-keto-DHEA in differentiated human THP-1 macrophages and in HEK-293 cells overexpressing 11beta-HSD1 with or without H6PDH. In contrast, 7-ketocholesterol (7-KC) did not inhibit 11beta-HSD1 in HEK-293 cells, even in the presence of H6PDH, but inhibited 11beta-HSD1 reductase activity in differentiated THP-1 macrophages (IC(50) 8.1+/-0.9microM). 7-Keto-DHEA but not 7-KC inhibited 11beta-HSD1 in HEK-293 cell lysates. In conclusion, cellular factors such as H6PDH can significantly modulate the effect of inhibitors and alternative 7-oxygenated substrates on intracellular glucocorticoid availability. DOI: 10.1016/j.mce.2008.10.021 PMID: 19010388 [Indexed for MEDLINE]
10. PLoS One. 2007 Jun 27;2(6):e561. doi: 10.1371/journal.pone.0000561. Hexose-6-phosphate dehydrogenase modulates 11beta-hydroxysteroid dehydrogenase type 1-dependent metabolism of 7-keto- and 7beta-hydroxy-neurosteroids. Nashev LG(1), Chandsawangbhuwana C, Balazs Z, Atanasov AG, Dick B, Frey FJ, Baker ME, Odermatt A. Author information: (1)Institute of Molecular and Systems Toxicology, University of Basel, Basel, Switzerland; Department of Nephrology and Hypertension, University of Berne, Berne, Switzerland. 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. Besides its role in glucocorticoid metabolism, there is evidence that 11beta-HSD1 is involved in the metabolism of 7-keto- and 7-hydroxy-steroids; however the impact of H6PDH on this alternative function of 11beta-HSD1 has not been assessed. METHODOLOGY: We investigated the 11beta-HSD1-dependent metabolism of the neurosteroids 7-keto-, 7alpha-hydroxy- and 7beta-hydroxy-dehydroepiandrosterone (DHEA) and 7-keto- and 7beta-hydroxy-pregnenolone, respectively, in the absence or presence of H6PDH in intact cells. 3D-structural modeling was applied to study the binding of ligands in 11beta-HSD1. PRINCIPAL FINDINGS: We demonstrated that 11beta-HSD1 functions in a reversible way and efficiently catalyzed the interconversion of these 7-keto- and 7-hydroxy-neurosteroids in intact cells. In the presence of H6PDH, 11beta-HSD1 predominantly converted 7-keto-DHEA and 7-ketopregnenolone into their corresponding 7beta-hydroxy metabolites, indicating a role for H6PDH and 11beta-HSD1 in the local generation of 7beta-hydroxy-neurosteroids. 3D-structural modeling offered an explanation for the preferred formation of 7beta-hydroxy-neurosteroids. CONCLUSIONS: Our results from experiments determining the steady state concentrations of glucocorticoids or 7-oxygenated neurosteroids suggested that the equilibrium between cortisone and cortisol and between 7-keto- and 7-hydroxy-neurosteroids is regulated by 11beta-HSD1 and greatly depends on the coexpression with H6PDH. Thus, the impact of H6PDH on 11beta-HSD1 activity has to be considered for understanding both glucocorticoid and neurosteroid action in different tissues. DOI: 10.1371/journal.pone.0000561 PMCID: PMC1891437 PMID: 17593962 [Indexed for MEDLINE] Conflict of interest statement: Competing Interests: The authors have declared that no competing interests exist.
11. Vitam Horm. 2005;71:263-99. doi: 10.1016/S0083-6729(05)71009-8. C(19)-5-ene steroids in nature. Lardy H(1), Marwah A, Marwah P. Author information: (1)Institute for Enzyme Research, Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53726, USA. 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. It is probably responsible for the growth of therapy-resistant prostate cancer. DHEA is hydroxylated at the 7 alpha position, and this derivative is oxidized by 11 beta-hydroxysteroid dehydrogenase to form 7-keto DHEA. The latter is reduced by the same dehydrogenase to form 7 beta-hydroxy DHEA. When fed to rats, each of the latter three steroids induce the formation of two thermogenic enzymes in the liver. The late-term human fetus produces relatively large amounts of 16 alphahydroxy DHEA, which serves the mother as a precursor of estriol. DOI: 10.1016/S0083-6729(05)71009-8 PMID: 16112271 [Indexed for MEDLINE]
12. Mini Rev Med Chem. 2003 Sep;3(6):557-67. doi: 10.2174/1389557033487953. 7-keto-delta(5)-steroids: key-molecules owning particular biological and chemical interest. Arsenou ES(1), Fousteris MA, Koutsourea AI, Nikolaropoulos SS. Author information: (1)Department of Pharmacy, School of Health Sciences, University of Patras, 265 00 Rion-Patra, Greece. 7-keto-Delta(5)-steroids have been suggested for the treatment of several diseases. Their significant biological profile resulted in the development of a great number of methods and reagents for the allylic oxidation of Delta(5)-steroids. These methods and the biological evaluation of the main oxidized Delta(5)-steroids are summarized. DOI: 10.2174/1389557033487953 PMID: 12871158 [Indexed for MEDLINE]
13. J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):245-51. doi: 10.1016/s0960-0760(02)00274-1. Prohormones and sport. Delbeke FT(1), Van Eenoo P, Van Thuyne W, Desmet N. Author information: (1)Doping Control Unit, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. frans.delbeke@rug.ac.be 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. Additionally contaminated nutritional supplements containing banned substances not indicated on the label were administered. The results of the excretion studies indicate that after the intake of amounts substantially lower than the recommended dose athletes can fail a doping test for periods up to 120 h. DOI: 10.1016/s0960-0760(02)00274-1 PMID: 12650722 [Indexed for MEDLINE]
14. Med Hypotheses. 2003 Mar;60(3):391-7. doi: 10.1016/s0306-9877(02)00409-7. 7-oxo-DHEA and Raynaud's phenomenon. Ihler G(1), Chami-Stemmann H. Author information: (1)Department of Medical Biochemistry and Medical Genetics, Texas A&M College of Medicine, College Station 77843, USA. gmihler@tamu.edu 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. Treatment of Raynaud's symptoms is conservative and aimed at prevention of attacks. Patients are advised to remain warm and, if possible, to live in warm climates. We suggest that an ergogenic (thermogenic) steroid, 7-oxo-DHEA (3-acetoxyandrost-5-ene-7,17-dione), which is available without prescription as the trademarked 7-keto DHEA, may be very helpful in prevention of primary Raynaud's attacks by increasing the basal metabolic rate and inhibiting vasospasm. DOI: 10.1016/s0306-9877(02)00409-7 PMID: 12581618 [Indexed for MEDLINE]
15. Probl Endokrinol (Mosk). 1979 Jul-Aug;25(4):28-31. [Excretion of testosterone, epitestosterone, androstenedione and 7-ketodehydroepiandrostenedione in healthy men of different ages]. [Article in Russian] Marenich LP. Urinary excretion of testosterone, epitestosterone, androstendion, and 7-keto-dehydroepistendion was studied in 34 healthy men, aged from 20 to 72 years. The maximal excretion of these steroids and observed in men, aged between 20 and 30 years; their reduction was noted with the advance of age. PMID: 157483 [Indexed for MEDLINE]
16. Kardiologiia. 1979 Jun;19(6):76-9. [Effect of chorionic gonadotropin on the urinary excretion of testosterone and other androgens in healthy men and those with coronary arteriosclerosis]. [Article in Russian] Marenich LP. The results of studying the excretion of testosterone and other androgens with the urine after a chorionic gonadotropin load in patients with ischemic heart disease and in persons who had suffered from acute myocardial infarction are discussed. In choriogonin load stimulating the gonads, there is noticeable variability in the excretion of testosterone and epitestosterone, androstenedione, and 7-keto-dehydroepiandrosterone in the urine. The data obtained are evidence of reduced functional reserves of the sex glands in some of the patients. PMID: 156806 [Indexed for MEDLINE]
17. Acta Med Acad Sci Hung. 1975;32(2):139-52. The metabolism of [4-14C]5-androstene-3 beta, 17 beta-diol by normal human skin in vitro. Faredin I, Tóth I. Healthy female and male abdominal skin slices were incubated with [4-14C]5-androstene-3 beta, 17 beta-diol. With a reverse isotope dilution method the following metabolites were isolated and identified: 5 alpha-androstane-3,17-dione, 4-androstene-3, 17-dione, 5 alpha-dihydrotestosterone, dehydroepiandrosterone, androsterone, testosterone, 7-keto-5-androstene-3beta, 17 beta-diol, 7 alpha-hydroxydehydroepiandrosterone sulphate and 5-androstene-3 beta, 17 beta-diol-3-sulphate. The amounts of the metabolites formed showed that [4-14C]5-androstene-3 beta, 17 beta-diol was metabolized in different ways by healthy female and male abdominal skin slices. In female skin the main direction of metabolism leads to the formation of androgenic steroids, while in male skin the main biosynthetic route is the C7-oxidation of the substrate. The fact that 5-androstene-3beta, 17 beta-diol is transformed to a considerable extent to testosterone and 5 alpha-dihydrotestosterone proves that in human skin 5-androstene-3 beta, 1m beta-diol is a better precursor of the androgenic steroids than dehydroepiandrosterone or 4-androstene-3, 17-dione. PMID: 1235221 [Indexed for MEDLINE]
18. Endokrinologie. 1975 Jan;64(2):213-6. [Steroid metabolism in primates. XVI. Secretion of corticosteroids in the baboon Papio hamadryas during chronic administration of sodium chloride]. [Article in German] Gontscharow NP, Simarina AJ, Jefremova SK, Schön R, Schubert K. 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. PIP: Adrenal steroid secretion was studied in 8 male baboons treated with sodium chloride for 1-3 years. In comparison with untreated animals, the secretion of progesterone, 17alpha-hydroxyprogesterone, 11-deoxycort isol, aldosterone, and corticosterone was decreased, while cortisone, pregnenolone, 7-keto-cholesterol, 7-keto-DHEA, DHEA, and adrenosterone secretion were increased. PMID: 125195 [Indexed for MEDLINE]
19. Steroids. 2016 Apr;108:112-7. doi: 10.1016/j.steroids.2016.02.005. Epub 2016 Feb 11. A validated LC-MS/MS method for the sensitive quantitation of serum 7alpha hydroxy-, 7beta hydroxy- and 7keto-dehydroepiandrosterone using a novel derivatization reagent. Ke Y(1), Gonthier R(1), Simard JN(1), Labrie F(2). Author information: (1)EndoCeutics Laboratory, 1405 Parc Technologique Blvd, Suite 250, Québec, QC G1P 4P5, Canada. (2)EndoCeutics Laboratory, 1405 Parc Technologique Blvd, Suite 250, Québec, QC G1P 4P5, Canada. Electronic address: fernand.labrie@endoceutics.com. 7alpha hydroxy-, 7beta hydroxy- and 7keto-dehydroepiandrosterone (7α OH-DHEA, 7β OH-DHEA and 7 oxo-DHEA) are oxidized metabolites of dehydroepiandrosterone (DHEA). Their concentrations are low in the circulation, especially in postmenopausal women, thus resulting in a considerable challenge for their reliable measurement. A sensitive and accurate LC-MS/MS method has been developed using a simple sample preparation procedure and a novel derivatization with 1-amino-4-methyl piperazine (MP). The derivatized metabolites are stable in high water content reagents. A 10 pg/mL (0.2 pg on column) for the low limit of quantitation (LLOQ) has been achieved for all three compounds. A proper choice of multiple reaction monitoring (MRM) transitions provides good specificity. The excess amount of reagent can be removed from the sample during the derivatization process. Within the calibration range of 10-2000 pg/mL, a good linearity was obtained with R>0.99 where the weighing factor is 1/X while the bias and coefficient of variance (CV) are within 8% for all levels of QCs and calibration curves. This method has been fully validated according to the FDA guidelines, where the results of the matrix effect meet the acceptance criteria while freeze-thaw stability, short and long term stability in matrix and solution as well as post-processed sample stability meet the requirements. With this method, the concentrations of 7α OH-DHEA, 7β OH-DHEA and 7 oxo-DHEA were measured in premenopausal and postmenopausal serum. The average concentration of 7α OH-DHEA is equivalent to that of 7β OH-DHEA in both types of sera. Copyright © 2016 Elsevier Inc. All rights reserved. DOI: 10.1016/j.steroids.2016.02.005 PMID: 26855361 [Indexed for MEDLINE]
20. Physiol Res. 2015;64(Suppl 2):S121-33. doi: 10.33549/physiolres.933073. Steroid hormones related to 11beta-hydroxysteroid dehydrogenase type 1 in treated obesity. Máčová L(1), Sosvorová L, Vítků J, Bičíková M, Hill M, Zamrazilová H, Sedláčková B, Stárka L. Author information: (1)Department of Steroids and Proteofactors, Institute of Endocrinology, Prague, Czech Republic. lmacova@endo.cz. The local concentration of glucocorticoids is intensively regulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1). Human 11beta-HSD 1 also reversibly catalyzes the inter-conversion of 7alpha-hydroxy- and 7beta-hydroxy-dehydroepiandrosterone (DHEA) into 7-oxo-DHEA. The cohort of 282 obese adolescents, 154 girls (median age 15.31 years, range 14.17-16.68 years) and 128 boys (median age 14.95 years, range 13.87-16.16 years), BMI (Body Mass Index) >90th percentile was examined. In samples collected before and after one month of reductive diet therapy, circulating levels of steroids were analyzed by liquid chromatography-tandem mass spectrometry and radioimmunoassay methods. The model of the treatment efficacy prediction was calculated. A significant reduction in circulating levels of cortisone, E2 and increased levels of 7beta-hydroxy-DHEA after the reductive treatment was observed. Levels of cortisol, DHEA, DHT sustained without any significant change. The predictive Orthogonal Projections to Latent Structures (OPLS) model explained 20.1 % of variability of BMI, z-score change by the basal levels of 7alpha-hydroxy-DHEA, DHEA, cortisol and E2 as the strongest predictors. Reduced levels of circulating cortisone and reduced ratios of oxygenated/reduced metabolites reflect increased reductase activity of 11beta-HSD 1 with reduced BMI, z-score. We hypothesize whether these changes can be attributed to the altered activity of 11beta-HSD 1 in the liver. DOI: 10.33549/physiolres.933073 PMID: 26680473 [Indexed for MEDLINE]
21. Physiol Res. 2014;63(1):95-101. doi: 10.33549/physiolres.932540. Epub 2013 Nov 1. Reduced levels of circulating 7alpha-hydroxy-dehydroepiandrosterone in treated adolescent obese patients. Máčová L(1), Bičíková M, Zamrazilová H, Hill M, Kazihnitková H, Sedláčková B, Stárka L. Author information: (1)Department of Steroids and Proteofactors, Institute of Endocrinology, Prague, Czech Republic. lmacova@endo.cz. Erratum in Physiol Res. 2014;63(3):393. Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD 1), an enzyme that regenerates active cortisol from inert cortisone. Increased expression of 11beta-HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11beta-HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-oxo-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7alpha-OH-DHEA, 7beta-OH-DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04-15.67 years, BMI greater than 90th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7alpha-OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854, transformed mean with 95 % confidence interval) to 1.530 nmol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1.842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1.132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7beta-OH-DHEA levels was observed. In conclusions, diminished levels of 7alpha-OH-DHEA indicate its possible effect on activity of 11beta-HSD 1. Further studies are necessary to clarify whether competitive substrates for 11beta-HSD 1 such as 7alpha-OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity. DOI: 10.33549/physiolres.932540 PMID: 24182335 [Indexed for MEDLINE]
22. Steroids. 2007 Apr;72(4):342-50. doi: 10.1016/j.steroids.2006.12.005. Epub 2006 Dec 20. A novel radioimmunoassay of 7-oxo-DHEA and its physiological levels. Kazihnitková H(1), Zamrazilová L, Hill M, Lapcík O, Pouzar V, Hampl R. Author information: (1)Institute of Endocrinology, Národní 8, 11694 Praha 1, Czech Republic. A novel radioimmunoassay (RIA) of unconjugated 7-oxo-dehydroepiandrosterone (7-oxo-DHEA) in human serum was developed for the first time. This steroid is an intermediate in the biosynthesis of immunomodulatory 7-hydroxylated DHEA metabolites, and has been shown to possess thermogenic properties. The method employs polyclonal rabbit antiserum to (19E)-3beta-hydroxy-7,17,19-trione-19-O-(carboxymethyloxime):BSA conjugate and a homologous radioiodinated derivative with tyrosine methyl ester. The cross reactivity of the antiserum with structurally closest 7-hydroxyepimers of DHEA was lower than 1.7%, with DHEA 0.4%, with all other related steroid less than 0.4%. The method includes ether extraction of serum (0.5 ml), followed by RIA. Its detection limit was 0.06 pmol (18 pg)/tube, the average intra- and inter-assay coefficients of variation were 4.1% and 8.3%, respectively. Mean recovery of serum spiked with 7-oxo-DHEA varied between 78.8% and 112%. Its levels in three serum pools were compared with a low-resolution gas chromatography-mass spectrometry method with satisfactory results. The method has been used for determination of 7-oxo-DHEA in serum samples of 215 subjects (91 males and 124 females) without overt endocrine disorders, aged 5-71 years. The over-all mean+/-S.D. was 0.280+/-0.227, the median 0.239 nmol/l. No significant sex differences were recorded. The only group which differed significantly from all other ones were males below 10 years, significantly lower values than in other age groups were found also in the first two age groups of females. DOI: 10.1016/j.steroids.2006.12.005 PMID: 17298836 [Indexed for MEDLINE]
23. Steroids. 2004 Dec;69(13-14):817-24. doi: 10.1016/j.steroids.2004.08.003. Simultaneous determination of dehydroepiandrosterone and its 7-oxygenated metabolites in human serum by high-resolution gas chromatography--mass spectrometry. Matsuzaki Y(1), Yoshida S, Honda A, Miyazaki T, Tanaka N, Takagiwa A, Fujimoto Y, Miyazaki H. Author information: (1)Department of Gastroenterology and Hepatology, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. ymatsuzaki-gi@umin.ac.jp A highly sensitive and specific method has been developed for the simultaneous measurement of free (unconjugated) or sulfate-conjugated forms of dehydroepiandrosterone (DHEA), 7alpha-hydroxy-DHEA (7alpha-OH-DHEA), 7beta-hydroxy-DHEA (7beta-OH-DHEA), and 7-oxo-DHEA (7-oxo-DHEA) in human serum. This method is based upon a stable isotope-dilution technique by gas chromatography-selected-ion monitoring mass spectrometry. Free steroids were extracted from serum with an organic solvent and the sulfate-conjugated steroids remained in aqueous phase. Free steroids were purified by solid-phase extraction, while sulfate-conjugated steroids were hydrolyzed by sulfatase and deconjugated steroids were purified by solid-phase extractions. The extracts were treated with O-methylhydroxylamine hydrochloride and were subsequently dimethylisopropylsilylated. The resulting methyloxime-dimethylisopropylsilyl (MO-DMIPS) ether derivatives were quantified by gas chromatography-selected-ion monitoring mass spectrometry in a high-resolution mode. The detection limits of MO-DMIPS ether derivatives of DHEA, 7alpha-OH-DHEA, 7beta-OH-DHEA and 7-oxo-DHEA were 1.0, 0.5, 0.5 and 2.0pg, respectively. Coefficients of variation between samples ranged from 10.6 to 22.9% for free 7-oxygenated DHEA to less than 10% for DHEA and sulfate-conjugated 7-oxygenated DHEA. The concentrations of these steroids were measured in 18 sera samples from healthy volunteers (9 males and 9 females; aged 23-78 years). Free DHEA, 7alpha-OH-DHEA, 7beta-OH-DHEA and 7-oxo-DHEA levels ranged between 0.21-3.55, 0.001-0.194, 0.003-0.481, and 0.000-0.077ng/ml, respectively, and the sulfate-conjugated steroid levels of these metabolites ranged between 253-4681, 0.082-3.001, 0.008-0.903, and 0.107-0.803ng/ml, respectively. The free DHEA-related steroid concentrations were much lower than those previously measured by RIA and low-resolution GC-MS. The present method made it possible to determine simultaneously serum DHEA-related steroid levels with sufficient sensitivity and accuracy. DOI: 10.1016/j.steroids.2004.08.003 PMID: 15582537 [Indexed for MEDLINE]
24. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Feb 15;767(2):285-99. doi: 10.1016/s1570-0232(01)00570-0. Ergosteroids. VI. Metabolism of dehydroepiandrosterone by rat liver in vitro: a liquid chromatographic-mass spectrometric study. Marwah A(1), Marwah P, Lardy H. Author information: (1)University of Wisconsin-Madison, Institute for Enzyme Research and Department of Biochemistry, 53705-4908, USA. Because relatively large amounts of dehydroepiandrosterone (DHEA) are required to demonstrate its diverse metabolic effects, it is postulated that this steroid may be converted to more active molecules. To search for the possible receptor-recognized hormones. DHEA was incubated with whole rat liver homogenate and metabolite appearances were studied by LC-MS as a function of time to predict the sequence of their formation. An array of metabolites has been resolved, identified and characterized by highly specific and accurate technique of LC-MS, and several of these steroids were analyzed quantitatively. Their identities were established by comparison with pure chemically synthesized compounds and by chemical degradation of isolated fractions. In the present study, we have reasonably established that DHEA was converted to 7alpha-OH-DHEA, 7-oxo-DHEA, and 7beta-OH-DHEA in sequence. These metabolites were further reduced at position 7 and/or 17 to form their respective diols and triols, which were also sulfated at 3beta-position. DHEA and its 7-oxygenated derivatives were also converted to their respective 3beta-sulfate esters. Several of these steroids are being reported for the first time. 16Alpha-hydroxy-DHEA, androst-5-ene-3beta,16alpha,17beta-triol, androst-4-ene-3,17-dione, 11-hydroxy-androst-4-ene-3,17-dione, androst-5-ene-3,17-diol and testosterone were also identified and characterized. In all, 19 metabolites of DHEA are being reported in this extensive study. We have also detected the formation of 12 additional metabolites including several conjugates, which are the subject of current investigation. DOI: 10.1016/s1570-0232(01)00570-0 PMID: 11885858 [Indexed for MEDLINE]
25. Biochem Biophys Res Commun. 1999 Jan 8;254(1):124-6. doi: 10.1006/bbrc.1998.9908. An escalating dose oral gavage study of 3beta-acetoxyandrost-5-ene-7, 17-dione (7-oxo-DHEA-acetate) in rhesus monkeys. Henwood SM(1), Weeks CE, Lardy H. Author information: (1)Covance Laboratories Inc., Madison, Wisconsin. To test the effects of 7-oxo-dehydroepiandrosterone-3 acetate (hereafter 7-ODA) in Rhesus macaques the steroid was administered by oral gavage to two male and two female monkeys. Dose levels of 250, 500, and 1,000 mg/kg body weight (BW)/day were administered on days 1, 3, and 5 respectively, and 1,000 mg/kg on days 7 through 11. Each group received the dose in a volume of 10 ml/kg BW. All animals survived to the scheduled sacrifice on day 12. No adverse clinical effects of 7-ODA were observed at the 250 or 500 mg/kg doses. Females vomited on non-treatment days and all animals vomited on some days after being given the 1000 mg/kg dose. Excessive salivation was observed before or immediately after dosing on days 9 through 11. Appearance, behavior and body weights were not altered by the treatments. Visual examination of all body cavities, and macroscopic and microscopic examination of 42 different organs and tissues found no lesions or abnormalities. Copyright 1999 Academic Press. DOI: 10.1006/bbrc.1998.9908 PMID: 9920744 [Indexed for MEDLINE]
26. Biochem Biophys Res Commun. 1999 Jan 8;254(1):120-3. doi: 10.1006/bbrc.1998.9907. An acute oral gavage study of 3beta-acetoxyandrost- 5-ene-7,17-dione (7-oxo-DHEA-acetate) in rats. Lardy H(1), Henwood SM, Weeks CE. Author information: (1)Institute for Enzyme Research, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA. The present study was done to assess the tolerance of rats for 3-acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate, 7-ODA) when administered as a single oral gavage dose. Five groups of Sprague-Dawley rats (Crl:CD (SD) BR VAF/Plus) (five/sex/group) were treated with 7-ODA at a dose level of 0 (control), 250, 500, 1000, or 2,000 mg/kg of body weight in a dose volume of 10 ml/kg. Food and water were provided ad libitum. All animals survived in good health to the scheduled sacrifice on Day 15. The single oral administration of 7-ODA had no apparent effects on body weight. Food consumption was significantly higher for all female treated groups during week two; however, the statistically significant differences were not considered to be of clinical consequence. Treatment caused no apparent changes of gross or microscopic anatomical structures of nine different organs. This study demonstrated that the no-observable adverse effect level for a single oral dose of 7-ODA in male and female rats was 2,000 mg/kg. Copyright 1999 Academic Press. DOI: 10.1006/bbrc.1998.9907 PMID: 9920743 [Indexed for MEDLINE]
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