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1.
Antisera for the radioimmunoassay of estrone and estradiol-17β in plasma are usually raised against estradiol-17β coupled to a protein through a derivative at carbon 17. Such antisera cross react with other naturally occurring estrogens, necessitating preliminary chromatographic separation. This difficulty could be overcome by the use of more specific antisera. We have raised antisera against the 6-0-carboxymethyloxime-bovine serum albumin (BSA) derivatives of estrone, estradiol-17β and estriol respectively. We have determined cross reactions with a number of estrogens and other naturally occurring steroids, and have compared the cross reactivity with that of an antiserum raised against estradiol-17β-17-succinyl-BSA. The former antisera show greatly reduced cross reaction with naturally occurring estrogens known or thought to be in relatively high concentration in plasma, as compared with the latter antiserum, but at the expense of greatly increased cross reaction with estrogens substituted at carbon 6. However, since these latter estrogens are thought to be in low concentration in plasma, the use of antisera raised against the 6-0-carboxymethyloxime-BSA derivatives should result in a net gain in specificity. The antisera raised against the estrone and estriol 6-0-carboxymethyloxime-BSA derivatives should be particularly useful. 相似文献
2.
Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. 相似文献
3.
Sobolevsky T Rodchenkov G 《The Journal of steroid biochemistry and molecular biology》2012,128(3-5):121-127
The biotransformation of dehydrochloromethyltestosterone (DHCMT, 4-chloro-17β-hydroxy,17α-methylandrosta-1,4-dien-3-one) in man was studied with the aim to discover long-term metabolites valuable for the antidoping analysis. Having applied a high performance liquid chromatography for the fractionation of urinary extract obtained from the pool of several DHCMT positive urines, about 50 metabolites were found. Most of these metabolites were included in the GC-MS/MS screening method, which was subsequently applied to analyze the post-administration and routine doping control samples. As a result of this study, 6 new long-term metabolites were identified tentatively characterized using GC-MS and GC-MS/MS as 4-chloro-17α-methyl-5β-androstan-3α,16,17β-triol (M1), 4-chloro-18-nor-17β-hydroxymethyl,17α-methyl-5β-androsta-1,13-dien-3α-ol (M2), 4-chloro-18-nor-17β-hydroxymethyl,17α-methyl-5β-androst-13-en-3α-ol (M3), its epimer 4-chloro-18-nor-17α-hydroxymethyl,17β-methyl-5β-androst-13-en-3α-ol, 4-chloro-18-nor-17β-hydroxymethyl,17α-methylandrosta-4,13-dien-3α-ol (M4) and its epimer 4-chloro-18-nor-17α-hydroxymethyl,17β-methylandrosta-4,13-dien-3α-ol. The most long-term metabolite M3 was shown to be superior in the majority of cases to the other known DHCMT metabolites, such as 4-chloro-18-nor-17β-hydroxymethyl,17α-methylandrosta-1,4,13-trien-3-one and 4-chloro-3α,6β,17β-trihydroxy-17α-methyl-5β-androst-1-en-16-one. 相似文献
4.
Charles L. Bevins Robert H. Kayser Ralph M. Pollack D.Belinda Ekiko Scott Sadoff 《Biochemical and biophysical research communications》1980,95(3):1131-1137
The spiro-17β-oxiranyl derivatives of d-equilenin, epiandrosterone, dehydroepiandrosterone, and Δ4-androsten-3,17-dione are active-site-directed irreversible inhibitors of Δ5-3-ketosteroid isomerase of . The 17β-oxiranyl steroids rapidly inhibit the isomerase in a time-dependent manner which exhibits saturation kinetics. The enzyme is protected against inactivation by the competitive inhibitor 19-nortestosterone. In addition, prolonged dialysis against neutral buffer leads to no regeneration of enzyme activity. Fluorescent spectral changes associated with the incubation of the enzyme with the 17β-oxirane derived from d-equilenin indicate that there are two modes of binding for steroids to the isomerase. These results suggest that 17β-oxiranes may inhibit the enzyme by a mechanism similar to that for the previously studied spiro-3β-oxiranyl steroids. 相似文献
5.
《Steroids》2014
Therapeutic potential of nandrolone and its derivatives against leishmaniasis has been studied. A number of derivatives of nandrolone (1) were synthesized through biotransformation. Microbial transformation of nandrolone (1) with Cunninghamella echinulata and Cunninghamella blakesleeana yielded three new metabolites, 10β,12β,17β-trihydroxy-19-nor-4-androsten-3-one (2), 10β,16α,17β-trihydroxy-19-nor-4-androsten-3-one (3), and 6β,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with four known metabolites, 10β,17β-dihydroxy-19-nor-4-androsten-3-one (5), 6β,17β-dihydroxy-19-nor-4-androsten-3-one (6) 10β-hydroxy-19-nor-4-androsten-3,17-dione (7) and 16β,17β-dihydroxy-19-nor-4-androsten-3-one (8). Compounds 1–8 were evaluated for their anti-leishmanial activity. Compounds 1 and 8 showed a significant activity in vitro against Leishmania major. The leishmanicidal potential of compounds 1–8 (IC50 = 32.0 ± 0.5, >100, 77.39 ± 5.52, 70.90 ± 1.16, 54.94 ± 1.01, 80.23 ± 3.39, 61.12 ± 1.39 and 29.55 ± 1.14 μM, respectively) can form the basis for the development of effective therapies against the protozoal tropical disease leishmaniasis. 相似文献
6.
Yoshizawa Itsuo Nagata Kyoko Ohuchi Ryoko Itoh Shinji Kanaiwa Yoshio Amiya Takashi 《Steroids》1980,36(1):87-96
Two D-homosteroids were isolated from the hydrolyzate of 5β-pregnane -3α,20α-diol disulfate (II) when it was refluxed in 3N hydrochloric acid. The structures of these steroids have been elucidated as 17α-methyl-D-homo-5β-androstane-3α, 17aβ-diol (VI) and 17α-methyl-17aγb-chloro-D-homo-5β-androstan-3α-ol (VIII) by instrumental analyses. The former was identical with a synthetic specimen derived from 5β-pregnane-3α,20β-diol di-sulfate (IV) by uranediol rearrangement. The main hydrolyzates obtained were 17α-ethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol (V) and 5β-pregnane-3α, 20α-diol (III). 相似文献
7.
19-Norandrosterone (19-NA) as its glucuronide derivative is the target metabolite in anti-doping testing to reveal an abuse of nandrolone or nandrolone prohormone. To provide further evidence of a doping with these steroids, the sulfoconjugate form of 19-norandrosterone in human urine might be monitored as well. In the present study, the profiling of sulfate and glucuronide derivatives of 19-norandrosterone together with 19-noretiocholanolone (19-NE) were assessed in the spot urines of 8 male subjects, collected after administration of 19-nor-4-androstenedione (100 mg). An LC/MS/MS assay was employed for the direct quantification of sulfoconjugates, whereas a standard GC/MS method was applied for the assessment of glucuroconjugates in urine specimens. Although the 19-NA glucuronide derivative was always the most prominent at the excretion peak, inter-individual variability of the excretion patterns was observed for both conjugate forms of 19-NA and 19-NE. The ratio between the glucuro- and sulfoconjugate derivatives of 19-NA and 19-NE could not discriminate the endogenous versus the exogenous origin of the parent compound. However, after ingestion of 100 mg 19-nor-4-androstenedione, it was observed in the urine specimens that the sulfate conjugates of 19-NA was detectable over a longer period of time with respect to the other metabolites. These findings indicate that more interest shall be given to this type of conjugation to deter a potential doping with norsteroids. 相似文献
8.
The scope and limitation of some recent acylation methods were investigated as applied to the preparation of steroidal esters of highly hindered acids. As representative steroids, 19-nor-17 alpha-ethinyl testosterone (19-NET) and testosterone, and as representative acid, pivalic (trimethylacetic) acid were used. 相似文献
9.
C E Cook T J Odiorne M C Dickey M E Twine E D Pellizzari M E Wall R Bressler 《Life sciences》1974,15(9):1621-1629
An analytical procedure for the estimation of norethindrone (17β-hydrox-19-nor-17α-pregn-4-en-20-yn-3-one) in human plasma has been developed. After extraction and purification on a silver ion exchange column, norethindrone is converted to a methoxime-trimethylsilyl ether derivative and measured by a gas chromatograph-mass spectrometer-accelerating voltage alternator system. Norethindrone-13C20,21?7?2H is used as a carrier and internal standard. Results correlated well with those obtained by radiochromatography. Maximum plasma levels of norethindrone in chronically treated and naive subjects ranged from 17–38 ng/ml. 相似文献
10.
Inhibition of human placental 17β-hydroxysteroid dehydrogenase by C18 and C19 steroids and nonsteroidal alcohols was assayed at pH 9.0 with 17β-estradiol 3-methyl ether and NAD+ as reactants. The nonstaroidal alcohols tested were poor inhibitors. Cyclopentanol and cyclohexanol had Ki values greater than 5 mm. Nonaromatic C18 and C19 steroids with oxygen functions at both positions 3 and 17 gave no detectable inhibition or had Ki, values greater than or equal to 160 μm. 3μ-Hydroxy-5,16-androstadiene, 5-androsten-3β-ol, 1,3,5(10)-estratrien-3-ol, and 1,3,5(10),16-estratetraen-3-ol, steroids lacking a C(17) oxygen function, had Ki values of 1.8, 6.0, 0.04, and 0.17 μm, respectively, demonstrating that both C18 and C19 steroids can bind at the steroid site. Binding specificity is narrowed and binding affinity for nonaromatic steroids weakened by oxygen functions at C(17) or both C(3) and C(17). The structural implications of the specificity data for steroid recognition and complex formation and in vivo control of enzyme activity are discussed. 相似文献
11.
The epimerization and dehydration reactions of the 17 beta-hydroxy group of anabolic 17 beta-hydroxy-17 alpha-methyl steroids have been investigated using the pyridinium salts of 17 beta-sulfate derivatives of methandienone 1, methyltestosterone 4, oxandrolone 7, mestanolone 10 and stanozolol 11 as model compounds. Rearrangement of the sulfate conjugates in buffered urine (pH 5.2) afforded the corresponding 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes in a ratio of 0.8:1. These data indicated that both epimerization and dehydration of the 17 beta-sulfate derivatives were not dependent upon the respective chemical features of the steroids studied, but were instead inherent to the chemistry of the tertiary 17 beta-hydroxy group of these steroids. Interestingly, in vivo studies carried out with human male volunteers showed that only methandienone 1, methyltestosterone 4 and oxandrolone 7 yielded the corresponding 17-epimers 2, 5 and 8 and the 18-nor-17,17-dimethyl-13(14)-enes 3, 6 and 9 in ratios of 0.5:1, 2:1 and 2.7:1, respectively. No trace of the corresponding 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes derivatives of mestanolone 10 and stanozolol 11 was detected in urine samples collected after administration of these steroids. These data suggested that the in vivo formation of the 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes derivatives of 17 beta-hydroxy-17 alpha-methyl steroids is also dependent upon phase I and phase II metabolic reactions other than sulfation of the tertiary 17 beta-hydroxyl group, which are probably modulated by the respective chemical features of the steroidal substrates. The data reported in this study demonstrate that the 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes are not artifacts resulting from the acidic or microbial degradation of the parent steroids in the gut as previously suggested by other authors, but arise from the rearrangement of their 17 beta-sulfate derivatives. Unchanged oxandrolone 7 was solely detected in the unconjugated steroid fraction whereas unchanged steroids 1, 4 and 11 were recovered from the glucuronide fraction. These data are indirect evidences suggesting that the glucuronide conjugates of compounds 1 and 4 are probably enol glucuronides and that of compound 11 is excreted in urine as a N-glucuronide involving its pyrazole moiety. The urinary excretion profiles of the epimeric and 18-nor-17,17-dimethyl-13(14)-ene steroids are presented and discussed on the basis of their structural features. 相似文献
12.
Metandienone is one of the most frequently detected anabolic androgenic steroids in sports drug testing. Metandienone misuse is commonly detected by monitoring different metabolites excreted free or conjugated with glucuronic acid using gas chromatography mass spectrometry (GC–MS) and liquid chromatography tandem mass spectrometry (LC–MS/MS) after hydrolysis with β-glucuronidase and liquid–liquid extraction. It is known that several metabolites are the result of the formation of sulphate conjugates in C17, which are converted to their 17-epimers in urine. Therefore, sulphation is an important phase II metabolic pathway of metandienone that has not been comprehensively studied. The aim of this work was to evaluate the sulphate fraction of metandienone metabolism by LC–MS/MS. Seven sulphate metabolites were detected after the analysis of excretion study samples by applying different neutral loss scan, precursor ion scan and SRM methods. One of the metabolites (M1) was identified and characterised by GC–MS/MS and LC–MS/MS as 18-nor-17β-hydroxymethyl-17α-methylandrost-1,4,13-triene-3-one sulphate. M1 could be detected up to 26 days after the administration of a single dose of metandienone (5 mg), thus improving the period in which the misuse can be reported with respect to the last long-term metandienone metabolite described (18-nor-17β-hydroxymethyl-17α-methylandrost-1,4,13-triene-3-one excreted in the glucuronide fraction). 相似文献
13.
Carbon isotope ratio (CIR) analysis of urinary steroids using gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS) is a recognized test to detect illicit doping with synthetic testosterone. There are currently no universally used steroid isotopic standards (SIS). We adapted a protocol to prepare isotopically uniform steroids for use as a calibrant in GCC-IRMS that can be analyzed under the same conditions as used for steroids extracted from urine. Two separate SIS containing a mixture of steroids were created and coded CU/USADA 33-1 and CU/USADA 34-1, containing acetates and native steroids, respectively. CU/USADA 33-1 contains 5α-androstan-3β-ol acetate (5α-A-AC), 5α-androstan-3α-ol-17-one acetate (androsterone acetate, A-AC), 5β-androstan-3α-ol-11, 17-dione acetate (11-ketoetiocholanolone acetate, 11k-AC) and 5α-cholestane (Cne). CU/USADA 34-1 contains 5β-androstan-3α-ol-17-one (etiocholanolone, E), 5α-androstan-3α-ol-17-one (androsterone, A), and 5β-pregnane-3α, 20α-diol (5βP). Each mixture was prepared and dispensed into a set of about 100 ampoules using a protocol carefully designed to minimize isotopic fractionation and contamination. A natural gas reference material, NIST RM 8559, traceable to the international standard Vienna PeeDee Belemnite (VPDB) was used to calibrate the SIS. Absolute δ13CVPDB and Δδ13CVPDB values from randomly selected ampoules from both SIS indicate uniformity of steroid isotopic composition within measurement reproducibility, SD(δ13C) < 0.2‰. This procedure for creation of isotopic steroid mixtures results in consistent standards with isotope ratios traceable to the relevant international reference material. 相似文献
14.
In the present report, the metabolism of dehydroepiandrosterone, 5-androstene-3β, 17β-diol and androstenedione has been studied in two different Shionogi tumors, one is androgendependent (“androgen sensitive”) and grows in intact male mice and the other is apparently androgen-independent (“androgen insensitive”) since the cells continue to grow in castrated antiandrogen (Flutamide) treated male animals. Our data clearly show that both the sensitive and insensitive tumors contain 3β-hydroxysteroid Δ5-Δ4 isomerase which causes the transformation of C19 steroids into potent androgenic steroids. However, the androgen sensitive tumor is able to convert 5-androstene-3β, l7β-diol into 2-hydroxyestrogens while the rate of conversion is extremely low in the insensitive tumor. Most interestingly, the production of 5α-reduced steroids observed in both tissues was clearly higher in insensitive tumor homogenates. 相似文献
15.
Vidrna L Černý I Pouzar V Borovská J Vyklický V Vyklický L Chodounská H 《Steroids》2011,76(10-11):1043-1050
Analogs of pregnanolone (3α-hydroxy-5β-pregnan-20-one), modified in position 17 were prepared. Compounds with 20-keto pregnane side chain replaced completely by azide (17α- and 17β-azido-5β-androstan-3α-ol), compounds with its part replaced (20-azido-21-nor-5β-pregnan-3α-ol), and compounds with keto group only replaced ((20R)- and (20S)-20-azido-5β-pregnan-3α-ol) were synthesized using tosylate displacements with sodium azide or Mitsunobu reaction with azoimide. All five azido steroids were converted into corresponding sulfates. Subsequent tests for inhibition of glutamate induced response on NMDA receptors revealed that modification of pregnanolone sulfate side chain with azide did not disturb the activity and some of sulfates tested were more active than parent compound. 相似文献
16.
Phytochemical investigation of the root of Streptocaulon griffithii Hook (Asclepiadaceae) led to the isolation of three unusual novel triterpenoids, 28, 29-nor-3β, 4β-dihydroxyl-9, 19-cycloartan-26-acid (1), 28, 29-nor-3β, 4β-dihydroxyl-9, 19-cycloartan- 26-acid methylester (2), a 30-nor-lupeol derivative 30-nor-3β-acetoxy-lupan-20-one (3) and five known compounds 4–8. Their structures were established on the basis of physical and spectroscopic analysis, including 1D and 2D NMR (1H, 13C, COSY, HSQC, and HMBC), ESI mass spectrometry, and by comparison with the NMR data published in the literature. The cytotoxicities of the isolated compounds against a panel of cultured tumor cell lines (Hela, PC3, SMMC7721, CNE) were evaluated. The new compounds 1 and 2 showed moderate activities with IC50 values of 11.76 ∼ 26.52 μg/mL, respectively. The result showed that triterpenoids are typical compounds of Streptocaulon genus, which could be useful as characteristic markers in chemotaxonomic research and might helpful for explaining the use of S. griffithii in traditional medicine. 相似文献
17.
Placental homogenates from guinea-pigs at 16, 20, 35 and 55 days gestation were incubated with 7α-3H-dehydroepiandrosterone and 4-14C-androstenedione and analyzed for conversion products by reverse isotope dilution methods. 14C-3α-Hydroxy-5α-androstan-17-one, 14C-androstane-3α, 17β-diol and 3Handrost-5-ene-3β, 17β-diol were isolated from homogenates incubated with substrates for 2 hours. 3H, 14C-Testosterone was isolated from preparations incubated for 15 minutes or with high substrate: tissue ratios. Androst-4-ene-3, 17-dione, 5α-androstane-3, 17-dione, 5β-androstanedione derivative and C18 steroid formation could not be demonstrated. These results demonstrate the capacity of guinea-pig placentas to convert dehydroepiandrosterone and androstenedione to testosterone and to derivatives reduced in ring A (5α) and at carbon 17. The activity of the Δ5-3β-hydroxysteroid dehydrogenase enzyme system appears to have been rate limiting.Homogenates of adrenals from 44–55 day old fetuses converted 4-14C-pregnenolone to androst-4-ene-3, 17-dione and 6β- and 11β-hydroxyandrostenedione. A guineapig fetal-placental unit is postulated, with steroid metabolic characteristics different from the human unit. Both permit reduction of fetal adrenal cortisol production and placental removal of C19 steroids. 相似文献
18.
The chemical synthesis of 16β-hydroxyandrosterone was described preparatory to studies of the disulphates of the 16-oxygenated ketonic C19 steroids present in the bile of female rats dosed with [3H]androsterone sulphate. The biliary metabolites were separated by chromatography on Sephadex LH-20 to afford monosulphate and dicon jugate fractions. After solvolysis of the diconjugate fraction, the liberated steroids were separated by partition chromatography on Celite 545 and analyzed by gas chromatography-mass spectrometry. In addition to 3α, 17β-dihydroxy-5α-androstan-16-one isolated previously, 16β-hydroxyandrosterone was identified as a disulphate. 相似文献
19.
[7β-3H]-(24R and 24S)-27-nor-24-methyl-3α,7α-dihydroxy-5β-cholestan-26-oic acids and [7β-3H]-27-nor-3α,7α-dihydroxy-5β-cholestan-26-oic acid (C27 and C26 bile acids having the same nuclear configuration as cheno-deoxycholic acid and its precursor, 3α,7α-dihydroxy-5β-cholestan-26-oic-acid) were synthesized and administered intraperitoneally to bile fistula guinea pigs. The biliary bile acids formed were hydrolyzed and analyzed by thin layer chromatography, and the metabolites were identified by the inverse isotope dilution method. The results showed that both (24R and 24S)-27-nor-24-methyl-3α,7α-dihydroxy-5β-cholestan-26-oic acids were not metabolized by the liver and were excreted unchanged as their taurine and glycine conjugates whereas 27-nor-3α,7α-dihydroxy-5β-cholestan-26-oic acid was converted to chenodeoxycholic acid. 相似文献
20.
The effect of position substituents on sulfuric acid-induced fluorescence of corticosteroids was examined. Of all the steroids tested, 11β,17α-dihydroxy-3-keto-4-androsten-17β-carboxylic acid gave the greatest relative fluorescence intensity with a value approximately four times that of cortisol. All but two steroids yielding relative fluorescence values greater than 2% of that of cortisol had an 11β-OH moiety. The two exceptions were 20α-hydroxy-4-pregnen-3-one and 20β-hydroxy-4-pregnen-3-one. The following characteristics were common to those steroids yielding sulfuric acid-induced fluorescence: All contained an oxygen substituent of carbon 20. At least one hydroxyl group was present on the side chain. If an 11-hydroxyl group occurred an additional hydroxyl oxygen was found at position 17 or 21 or both. If an 11-hydroxylated substituent was absent, then positions 17 and 21 were both devoid of oxygen. The 18-aldehyde group or Δ1 unsaturation strongly suppressed fluorescence. 相似文献