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Journal of Chromatography. B,... Mar 2018Androstenedione is an androgen and intermediate in the biosynthesis of most adrenocortical, anabolic, sex and synthetic steroids, such as canrenone, eplerenone,...
Refining androstenedione and bisnorcholenaldehyde from mother liquor of phytosterol fermentation using macroporous resin column chromatography followed by crystallization.
Androstenedione is an androgen and intermediate in the biosynthesis of most adrenocortical, anabolic, sex and synthetic steroids, such as canrenone, eplerenone, norethindrone and spironolactone. Bisnorcholenaldehyde is an important intermediate in the synthesis of progesterone. This study established an androstenedione and bisnorcholenaldehyde separation method that used a macroporous adsorption resin and an ethanol-water mixture as eluent. The adsorption properties of 12 non-polar or weakly polar macroporous adsorption resins were compared, and three resins exhibited a high adsorption capacity and high desorption rate for both androstenedione and bisnorcholenaldehyde. The three resins were then compared using column chromatography, and one resin was selected and parameters (flow rate, resin size, ethanol concentration and volume) of chromatography were optimized to obtain high purity and recovery. Chromatography eluate was concentrated, dissolved in suitable solvent and crystallized at an optimal temperature to obtain a high purity of both androstenedione and bisnorcholenaldehyde from the same starting material. The levels of androstenedione and bisnorcholenaldehyde in the raw material were 39.78% and 19.15%, respectively. After preparative separation and enrichment by resin column chromatography and crystallization, the purity of androstenedione and bisnorcholenaldehyde was 94.3% and 98.6%, respectively, with their recovery yields of 66.8% and 57.9%, respectively. In addition, the resin maintained over 90% separation efficiency for 5 cycles of adsorption. These results indicated that the combination of macroporous resin chromatography followed by crystallization provide a simple, effective, environmentally friendly and low-cost method for the simultaneous purification of androstenedione and bisnorcholenaldehyde.
Topics: Adsorption; Androstenedione; Crystallization; Ethanol; Fermentation; Phytosterols; Polymers; Porosity; Pregnenes; Solvents; Water
PubMed: 29425789
DOI: 10.1016/j.jchromb.2017.09.032 -
Food and Chemical Toxicology : An... Jun 2004This study was conducted to characterize the effect of androstenedione on estrous cyclicity, mating behavior and fetal development. Thirty-day old rats received corn oil...
This study was conducted to characterize the effect of androstenedione on estrous cyclicity, mating behavior and fetal development. Thirty-day old rats received corn oil alone or androstenedione (in corn oil) at one of four concentrations (0, 1.0, 5.0, 10.0 or 30.0 mg/kg body weight) by gavage for two weeks prior to mating, during the mating period and throughout gestation. Dose related increases in serum androstenedione, estradiol and estrone were observed in all androstenedione treated animals at gestation day 20. A statistically significant increase in serum testosterone concentration was observed in the 30 mg/kg dose group. Feed and fluid consumption were not affected by androstenedione treatment during the pre-mating or gestational periods, however a statistically significant decrease in the number of females with regular estrous cycles was observed in the 10.0 and 30.0 mg/kg dose groups. Exposure to androstenedione did not affect mean body weight gain during pre-mating or gestation. Slight not statistically significant reductions in the number of implants, number of viable fetuses and number of viable male fetuses were observed in the 30.0 mg/kg androstenedione group. Reductions were not observed in the number of corpora lutea. Fetal growth in terms of fetal weight, crown-rump length, anogenital distance and the number of external abnormalities was not affected by androstenedione exposure. At the doses given, androstenedione had no specific effect on the development of individual bones, including sternebrae. Dose related effects of androstenedione were not observed on the development of soft tissues. A statistically significant increase in moderately enlarged ureter at the kidney was observed in both the 1.0 and 5.0 mg/kg dose groups. Organ weights (expressed per gram of body weight or per gram of brain weight) were not affected by androstenedione treatment.
Topics: Administration, Oral; Androstenedione; Animals; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Estrus; Female; Male; Rats; Sexual Behavior, Animal
PubMed: 15110100
DOI: 10.1016/j.fct.2004.01.015 -
Toxicological Sciences : An Official... May 2003The Fenholloway River near Perry, Florida, receives effluent from a paper mill and contains populations of masculinized female eastern mosquitofish, Gambusia holbrooki....
The Fenholloway River near Perry, Florida, receives effluent from a paper mill and contains populations of masculinized female eastern mosquitofish, Gambusia holbrooki. A previous study identified the androgen precursor androstenedione at a low concentration (0.14 nM) in water samples from the river. The present study makes use of a toxicity identification and evaluation approach that includes solid phase extraction and high pressure liquid chromatography purification, androgen receptor transcription assays, and liquid chromatography mass spectroscopy to identify and characterize steroids in the Fenholloway River sediment. Androstenedione (2.4 nM) and progesterone (155 nM) were identified in the river sediment at concentrations greater than in the river water column (0.14 nM androstenedione, and 6.5 nM progesterone). Spring Creek, a comparison stream that does not receive mill effluent, contained low levels of progesterone (0.3 nM) but no androstenedione in the sediment. The data are consistent with the hypothesis that pine pulp-derived phytosteroids in the paper mill effluent accumulate in river sediment where they are converted by microbes into progesterone and this into androstenedione and other bioactive steroids. Equally important is that normal streams with much less organic matter still contain progesterone, but at dramatically lower levels. The presence of androgens and androgen precursors in the river water and sediment likely contributes to the masculinized phenotype of the female Gambusia holbrooki in the Fenholloway River.
Topics: Androstenedione; Animals; Cell Line; Chromatography, High Pressure Liquid; Florida; Haplorhini; Industrial Waste; Industry; Kidney; Mass Spectrometry; Paper; Progesterone; Receptors, Androgen; Transcription, Genetic; Water Pollutants, Chemical
PubMed: 12700410
DOI: 10.1093/toxsci/kfg042 -
Physical Medicine and Rehabilitation... Nov 2000Supplements that are marketed as ergogenic aids have achieved widespread use in the United States. In image-conscious society, these agents are not only being consumed... (Review)
Review
Supplements that are marketed as ergogenic aids have achieved widespread use in the United States. In image-conscious society, these agents are not only being consumed by athletes, but also by those looking for a quick fix to enhance their appearance. Many assume that the performance claims made by the manufacturers are based on actual data, and that these agents must be safe because they are sold to the general public. Unfortunately, in most cases these assumptions are false. Creatine has become very popular, particularly among college and high school athletes. Studies within the last 5 years have shown that creatine does seem to have certain ergogenic benefits in a laboratory setting. It is not currently known whether these benefits actually can be transferred to the playing field. Although creatine has not consistently been shown to cause any major side effects, there is some question regarding creatine's effect on the kidneys, particularly with long-term use. Also, the safety of supplementation in children and adolescents has not been examined at all; its use in this population should be discouraged until there are more data. Androstenedione is an agent that has received a large amount of popular press in the last year, and this has led to an surge in its usage. It is believed to exert its ergogenic effects through conversion to testosterone. But what limited data are available suggest that at the recommended dosage, it does not cause any measurable change in testosterone levels, or provide any ergogenic benefit in inexperienced weight lifters. Also, it has yet to be determined whether androstenedione causes any of the side effects often attributed to use of the illegal anabolic steroids. Its mechanism of action suggests it has the potential to cause many of these negative effects. Studies are just beginning to appear in the literature, and certainly more data need to be gathered before androstenedione supplementation can be recommended for use as an ergogenic aid.
Topics: Androstenedione; Creatine; Dietary Supplements; Humans; Sports
PubMed: 11092026
DOI: No ID Found -
Journal of Enzyme Inhibition and... Oct 2011The aim of this study was to determine the capacity of some progesterone derivatives, to inhibit the conversion of labeled androstenedione ([(3)H] 4-dione) to...
The aim of this study was to determine the capacity of some progesterone derivatives, to inhibit the conversion of labeled androstenedione ([(3)H] 4-dione) to [(3)H]dihydrotestosterone ([(3)H]DHT) in prostate nuclear membrane fractions, where the 5α-reductase activity is present. The enzyme 5α-reductase catalyzes the 5α-reduction of 4-dione whereas the 17β-hydroxysteroid dehydrogenase catalyzes the transformation of 4-dione to testosterone or 5α-dione to dihydrotestosterone (DHT). Moreover, we also investigated the role of unlabeled 5α-dione in these pathways. In order to determine the inhibitory effect of different concentrations of the progesterone derivatives in the conversion of [(3)H] 4-dione to [(3)H]DHT, homogenates of human prostate were incubated with [(3)H] 4-dione, NADPH and increasing concentrations of non-labeled 5α-dione. The incubating mixture was extracted and purified using thin layer chromatography. The fraction of the chromatogram corresponding to the standard of DHT was separated and the radioactivity determined. The results showed that the presence of [(3)H] 4-dione plus unlabelled 5α-dione produced similar levels of DHT as compared to [(3)H] 4-dione. On the other hand, the results indicated that 17α-hydroxypregn-4-ene-3,20-dione 5 and 4-bromo-17α-hydroxypregn-4-ene-3,20-dione 7b, were the most potent steroids to inhibit the conversion of [(3)H] 4-dione to [(3)H]DHT, showing IC(50) values of 2 and 1.6 nM, respectively.
Topics: 5-alpha Reductase Inhibitors; Adult; Androstenedione; Enzyme Activation; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Male; Molecular Structure; Nuclear Envelope; Prostate
PubMed: 21299452
DOI: 10.3109/14756366.2010.548330 -
JAMA Jun 1999Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However,... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
CONTEXT
Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known.
OBJECTIVES
To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function.
DESIGN AND SETTING
Eight-week randomized controlled trial conducted between February and June 1998.
PARTICIPANTS
Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training.
INTERVENTIONS
Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n = 10), or placebo (n = 10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men.
MAIN OUTCOME MEASURES
Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration.
RESULTS
Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation.
CONCLUSIONS
Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.
Topics: Administration, Oral; Adult; Analysis of Variance; Androstenedione; Biopsy, Needle; Body Composition; Dietary Supplements; Double-Blind Method; Estrogens; Exercise; Humans; Lipids; Liver Function Tests; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Nutrition Assessment; Testosterone; Transaminases
PubMed: 10359391
DOI: 10.1001/jama.281.21.2020 -
JAMASeveral anabolic steroids are sold over-the-counter (OTC) in the United States, and their production is not regulated by the US Food and Drug Administration. Reports... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
CONTEXT
Several anabolic steroids are sold over-the-counter (OTC) in the United States, and their production is not regulated by the US Food and Drug Administration. Reports have suggested that use of these supplements can cause positive urine test results for metabolites of the prohibited steroid nandrolone.
OBJECTIVES
To assess the content and purity of OTC androstenedione and to determine if androstenedione and 19-norandrostenedione administration causes positive urine test results for 19-norandrosterone, a nandrolone metabolite.
DESIGN
Randomized controlled trial of androstenedione, open-label trial of 19-norandrostenedione, and mass spectrometry of androstenedione preparations, conducted between October 1998 and April 2000.
SETTING
Outpatient facility of a university hospital.
PARTICIPANTS
A total of 41 healthy men aged 20 to 44 years.
INTERVENTION
Participants were randomly assigned to receive oral androstenedione, 100 mg/d (n = 13) or 300 mg/d (n = 11) for 7 days, or no androstenedione (n = 13); in addition, 4 patients received 10 microg of 19-norandrostenedione.
MAIN OUTCOME MEASURES
Content of OTC androstenedione preparations; level of 19-norandrosterone in urine samples, determined by mass spectrometry, compared among the 3 randomized groups at day 1 and day 7, and among the participants who received 19-norandrostenedione from October 1998 to April 2000.
RESULTS
All urine samples from participants treated with androstenedione contained 19-norandrosterone, while no samples from the no-androstenedione group did. Urinary concentrations were averaged for day 1 vs day 7 measurements; mean (SD) 19-norandrosterone concentrations in the 100-mg/d and 300-mg/d groups were 3.8 (2.5) ng/mL and 10.2 (6.9) ng/mL, respectively (P =. 006). The 19-norandrosterone content exceeded the cutoff for reporting positive cases (>2.0 ng/mL) in 20 of 24. The androstenedione preparation used was pure at a sensitivity of 0.1%, but at 0.001% 19-norandrostenedione was found. For the 4 participants to whom 10 microg of 19-norandrostenedione was administered, 19-norandrosterone was found in all urine samples. Of 7 brands of androstenedione analyzed at the 1% level, 1 contained no androstenedione, 1 contained 10 mg of testosterone, and 4 more contained 90% or less of the amount stated on the label.
CONCLUSION
Our study suggests that trace contamination of androstenedione with 19-norandrostenedione is sufficient to cause urine test results positive for 19-norandrosterone, the standard marker for nandrolone use. Oral steroid doses as small as 10 microg are absorbed and excreted in urine. Some brands of androstenedione are grossly mislabeled. Careful analysis of androstenedione preparations is recommended in all studies of its biological effects. JAMA. 2000;284:2618-2621.
Topics: Adult; Anabolic Agents; Androstenedione; Dietary Supplements; Drug Contamination; Estranes; Humans; Male; Mass Spectrometry; Nandrolone; Nonprescription Drugs; Substance Abuse Detection; United States; Urinalysis
PubMed: 11086369
DOI: 10.1001/jama.284.20.2618 -
Proceedings of the National Academy of... May 1987Spotted hyenas (Crocuta crocuta Erxleben) present a unique syndrome of reversal in behavioral and anatomical distinction between the sexes: females are heavier and more...
Spotted hyenas (Crocuta crocuta Erxleben) present a unique syndrome of reversal in behavioral and anatomical distinction between the sexes: females are heavier and more aggressive than males and dominant over them. The female's external genitalia include a false scrotum and a fully erectile pseudopenis through which mating and birth take place. Results of studies of circulating testosterone levels in wild spotted hyenas do not account for the "male-like" characteristics of the female. Androstenedione, however, is consistently higher in females than in males, particularly during early infancy. Experiments on rodents show that androstenedione can be a potent organizer of anatomical and behavioral differentiation. This study suggests that it may also produce the profound virilization of female spotted hyenas.
Topics: Aging; Androstenedione; Animals; Carnivora; Disorders of Sex Development; Female; Male; Ovariectomy; Sex Characteristics; Sexual Maturation; Testosterone
PubMed: 3472215
DOI: 10.1073/pnas.84.10.3444 -
Fertility and Sterility Jul 2005To report a case of androstenedione (A)-induced impotence and severe oligospermia.
OBJECTIVE
To report a case of androstenedione (A)-induced impotence and severe oligospermia.
DESIGN
Case report.
SETTING
Multispecialty tertiary referral center.
PATIENT(S)
A 29-year-old married male recreational bodybuilder using the legal dietary supplement A in an attempt to enhance athletic performance.
INTERVENTION(S)
Immediate cessation of oral A, Depo-T regimen with a taper, administered during 3 months, to alleviate loss of libido and impotence.
MAIN OUTCOME MEASURE(S)
Resolution of symptoms and normalization of semen parameters.
RESULT(S)
Resolution of symptoms and normalization of semen parameters at 6 months, and successful intrauterine pregnancy achieved 1 year after initial presentation.
CONCLUSION(S)
Oral A has a previously unrecognized side effect, which is the potential to suppress the hypothalamic pituitary gonadal axis.
Topics: Administration, Oral; Adult; Androstenedione; Erectile Dysfunction; Humans; Male; Oligospermia
PubMed: 16009183
DOI: 10.1016/j.fertnstert.2005.01.125 -
JAMA Feb 2000
Topics: Adult; Androstenedione; Dietary Supplements; Exercise; Humans; Male; Muscle, Skeletal
PubMed: 10683045
DOI: No ID Found