Δ4-アンドロステン-3,17-ジオン

DEA Schedule III Controlled Substance -> Anabolic steroids

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

log Kow = 2.75

2.75

In water, 57.3 mg/L at 25 °C, pH 7.3; 40 mg/L at 37 °C, pH 7.4

In water, 66 mg/L at 20 °C, pH 6.5 (EU Method A.6, Water Solubility, flask method)

0.0578 mg/mL

Danger

H302 (97.9%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P263, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 48 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard Traits - Carcinogenicity

DEA schedule III controlled substance

Status: Active Update: 15-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/13632

Androstenedione: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Anabolic Steroids. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation containing any quantity of the following substances, including its salts, esters and ethers. Anabolic steroids /including 4-androstenedione/, DEA Code 4000, is included on this list.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Concentrations of intratesticular (IT) testosterone (T) are known to be 100-200 times those of serum T; however, the IT concentrations of T's precursors, their testicular to serum gradients, gonadotropin dependence, and response to stimulation with human chorionic gonadotropin (hCG) have not been studied in detail. We hypothesized that serum and IT androstenedione (ADD) and IT dehydroepiandrosterone (DHEA) would be significantly suppressed by the administration of a GnRH antagonist and increased when stimulated by hCG, without a similar suppression of serum DHEA. We suppressed gonadotropins in 23 normal men with the GnRH antagonist acyline and randomly assigned them to one of four doses of hCG, 0, 15, 60, or 125 IU sc every other day for 10 d. Blood and IT fluid for the measurement of serum and IT hormones were obtained at baseline and after 10 d of treatment. Baseline IT ADD [median (25th, 75th percentile)] was 629 (308, 860) nmol/liter, and IT DHEA was 564 (411, 879) nmol/liter, which were 175 and 27 times higher than their respective serum concentrations. IT ADD and IT DHEA were suppressed by 98 and 82%, respectively, by acyline and significantly increased with hCG administration. Likewise, serum ADD was suppressed by 50%, but serum DHEA was unchanged. ADD and DHEA are highly concentrated within the human testes compared with serum. Serum and IT ADD and IT DHEA are markedly suppressed with GnRH administration and stimulated by hCG, but serum DHEA is not, suggesting that most circulating DHEA is not of testicular origin.

Anticoagulant effects of coumarin- or indandione-derivative or anti-inflammatory analgesics, nonsteroidal or salicylates, in therapeutic doses may be increased during concurrent use with anabolic steroids, especially 17-alpha-alkylated compounds, because of decreased procoagulant factor concentration caused by alteration of procoagulant factor synthesis or catabolism and increased receptor affinity for the anticoagulant; anticoagulant dosage adjustment based on prothrombin time determinations may be required during and following concurrent use with anabolic steroids. /Anabolic Steroids/

Concurrent use of antidiabetic agents, sulfonylurea or insulin with anabolic steroids may decrease blood glucose concentration; diabetic patients should be closely monitored for signs of hypoglycemia ... /Anabolic Steroids/

Concurrent use of corticosteroids, glucocorticoid, especially with significant mineralocorticoid activity, prolonged therapeutic corticotropin or sodium-containing medications or foods with anabolic steroids may increase the possibility of edema; in addition, concurrent use of glucocorticoids or corticotropin with anabolic steroids may promote development of severe acne. /Anabolic Steroids/

For more Interactions (Complete) data for Androstenedione (7 total), please visit the HSDB record page.

Androstenedione was legally defined as an anabolic steroid by the FDA in 2004. It poses significant health risks commonly associated with steroids. The side effects for men include breast development, behavioral changes, heart disease, and more. Side effects for women are similar to the side effects from anabolic steroids in that their voices will deepen and they may grow facial hair since both occur from an increase level of testosterone. Another side effect of androstenedione is male pattern baldness. The main psychological side effect of androstenedione is depression. Mood swings are also common. Chronically high levels of androstenedione are associated with male pseudohermaphrodism with gynecomastia, Adrenal Hyperplasia Type 3 and Aromatase deficiency.

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of 6170(2) indicates that androstenedione is expected be immobile in soil(SRC). Volatilization of androstenedione from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.7X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Androstenedione is not expected to volatilize from dry soil surfaces(SRC) based upon an extrapolated vapor pressure of 7.35X10-9 mm Hg at 20 °C(4). Using OECD Guideline 301B (CO2 Evolution Test) with a non-adapted activated sludge inoculum, androstenedione reached 79-95% degradation over a 28-day incubation period which classified the compound as readily biodegradable(4). Based on the results of soil column studies with various soils and sands(2), the estimated half-life of androstenedione ranged from 1.7 to 77 hours(SRC). Androstenedione absorbs at wavelenghts >290 nm(5), and direct photolysis tests in water(5) suggest that androstenedione is expected to be susceptible to photodegradation on soil surfaces exposed to sunlight(SRC).

AQUATIC FATE: Based on a classification scheme(1), a Koc value of 6170(2) indicates that androstenedione is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.7X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 30(SRC), from a log Kow of 2.75(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low to moderate(SRC). Using OECD Guideline 301B (CO2 Evolution Test) with a non-adapted activated sludge inoculum, androstenedione reached 79-95% degradation over a 28-day incubation period which classified the compound as readily biodegradable(7). Androstenedione absorbs at wavelenghts >290 nm(8), and, therefore, may be susceptible to direct photolysis at water surfaces exposed to sunlight(SRC). In photodegradation studies in aqueous solution, androstenedione underwent direct photolysis half-lives ranging from 3.7 to 10.8 hours in direct sunlight(8). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(3).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), androstenedione, which has an extrapolated vapor pressure of 7.35X10-9 mm Hg at 20 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase androstenedione is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3.5 hours(SRC), calculated from its rate constant of 1.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Vapor-phase androstenedione is also degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 1 day(SRC), calculated from its rate constant of 1.1X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase androstenedione may be removed from the air by wet and dry deposition(SRC). Androstenedione absorbs at wavelenghts >290 nm(4), and therefore, may be susceptible to direct photolysis(SRC). Androstenedione underwent direct photolysis half-lives ranging from 3.7 to 10.8 hours in aqueous solution via sunlight exposure(4).

IDENTIFICATION AND USE: Androstenedione is a synthetic analog of androgens, formerly used as a dietary supplement. HUMAN STUDIES: There are cases of androstenedione-induced impotence and severe oligospermia. The effects of androstenedione supplementation on the hormonal profile of 10 males and its interaction with resistance exercise have been studied. Exercise elevated testosterone, with no difference between conditions. Exercise in the supplemented condition significantly elevated plasma estradiol by approximately 83% for 90 min. Androstenedione supplementation, thus, is unlikely to provide male athletes with any anabolic benefit and, with heavy resistance exercise, elevates estrogen. Other study suggested that oral androstenedione, when given in dosages of 300 mg/day, increased serum testosterone and estradiol concentrations in some healthy men. However, supplementation does result in significant increases in estrogen-related compounds, dehydroepiandrosterone sulfate concentrations, down-regulation in testosterone synthesis, and unfavorable alterations in blood lipid and coronary heart disease risk profiles of men aged 35 to 65 years. ANIMAL STUDIES: Androstenedione did not reveal a skin sensitization potential when tested in a guinea pig maximization test with a concentration of 5% for intradermal induction and 25% for epicutaneous induction and challenge following. Eye irritation was reported in rabbits. A single oral dose of androstenedione to male rats caused mortality at 1000 mg/kg, whereas animals survived at 500 mg/kg. Compound-related clinical signs were apathy, disturbance of gait and squatting position. At the lethal dose, additional signs included prone position, unconsciousness, disturbance in respiration and increased diuresis. The once daily oral administration of androstenedione to male and female rats over 4 weeks at doses of 0, 15, 50 and 150 mg/kg led to dose-dependent effects in females, such as increased body weight, atrophy of uterus, cervix, pituitary gland and adrenals, as well as increased numbers of erythrocytes and increased hemoglobin. For males alterations in thymus were reported. These effects were regarded to represent endocrine effects typical for a steroid hormone. Infusion of androstenedione to pregnant monkeys resulted in the premature occurrence of labor-type myometrial activity and increases in maternal plasma estrogen, oxytocin and amnion fibronectin concentrations similar to those measured at normal-term labor. In rats, androstenedione had no specific effect on the development of individual bones or soft tissues. Androstenedione did not show a mutagenic potential in a bacterial reverse mutation assay according to OECD TG 471 (Ames test in S. typhimurium TA98, TA1537, TA100, TA102, TA1535) when tested up to the highest recommended dose level of 5.0 mg/plate in the absence or presence of metabolic activation. ECOTOXICITY STUDIES: Exposure to androstenedione via water can cause masculinization of adult female mosquitofish in a relatively short period of time. Exogenous androstenedione, at environmentally relevant concentrations, can significantly modulate the reproductive physiology of the fathead minnows in a sex-specific manner.

Androstenedione is converted to testosterone and estrogen, and when taken in sufficient quantities androstenedione can cause unwanted masculinizing and feminizing effects. Androstenedione is considered an androgenic steroid precursor because testosterone is an androgen or male hormone. In males, conversion of androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase. In females, conversion of androstenedione to estrogen (e.g., estrone and estradiol) requires the enzyme aromatase.

/AQUATIC SPECIES/ In this study, ...the capacity of androstenedione to masculinize female mosquitofish /was investigated/. Previous studies have identified androstenedione in the water and sediment of the Fenholloway River, a Florida, USA, coastal river that receives paper mill effluent and contains masculinized eastern mosquitofish (Gambusia holbrooki). Females of the closely related western mosquitofish, Gambusia affinis, were exposed to androstenedione through both dietary and static renewal treatments. Morphological masculinization of female mosquitofish is characterized by the development of a male secondary sexual trait: an elongated and modified anal fin (gonopodium). Dietary exposure to 0.7, 7, 70, and 700 ug of androstenedione per gram of food failed to induce gonopodial development at any concentration within the six-week exposure period. Static renewal treatments used androstenedione concentrations of 0.14, 1.4, 14, 140, and 350 nM. Significant anal fin ray elongation was observed in all but the lowest exposure group. Fish growth during the static renewal exposure experiment was negatively correlated with androstenedione concentration. No significant effects were observed for gonadosomatic index, vitellogenin expression, or ovarian area in fish exposed to androstenedione via either the dietary or static renewal methods. These results indicate that exposure to androstenedione via water can cause masculinization of adult female mosquitofish in a relatively short period of time and that acute dietary exposure to androstenedione at the concentrations used is not sufficient to induce masculinization.

/AQUATIC SPECIES/ High concentrations (300 ng/L) of androstenedione (A4) were identified in snowmelt runoff from fields fertilized with manure from livestock feeding operations in Wisconsin, USA. In fishes, A4 is an active androgen and substrate for biosynthesis of functional androgens (e.g., testosterone and 11-ketotestosterone) and estrogens (e.g., estradiol-17beta). Thus, A4 has the potential to be a powerful endocrine disruptor. This hypothesis was tested by exposing reproductively mature fathead minnows to 0.0 ng/L, 4.5 ng/L, 74 ng/L, and 700 ng/L A4 for 26 days in a flow-through system. Various reproductive endpoints were measured including fecundity, fertilization success, secondary sexual characteristics, gonadosomatic index (GSI), and hepatic vitellogenin messenger RNA (mRNA) expression. In addition, fertilized embryos from the reproduction assay were used in an embryonic development assay to assess A4 effects on development and hatchability. In males, A4 significantly increased Vtg mRNA expression (estrogenic effect), significantly reduced GSI, and had no effect on tubercle expression (p=0.067). In females, A4 induced tubercle development (androgenic effect) with no effects on GSI. Fecundity was not significantly impacted. Exposure to A4 had no effect on fertilization, embryonic development, or hatchability. These data indicate that exogenous A4, at environmentally relevant concentrations, can significantly modulate the reproductive physiology of the fathead minnows in a sex-specific manner and that A4 should be monitored as an endocrine disruptor.

/AQUATIC SPECIES/ Standard reproductive assays with daphnids involve parthenogenetically reproducing females and exclude the assessment of effects on sexual reproduction. The goals of this study were to characterize sexual differentiation of male and female daphnids (Daphnia magna) and to evaluate whether exposure to putative endocrine-disrupting chemicals may perturb the development of sex characteristics. Anatomical sex differences that developed during maturation in males included elongated first antennae and morphologic alterations in the head capsule and carapace edge. Reproductive maturation in females was associated with the development of a brood chamber and abdominal process. Alterations in the growth rates of the first antennae of males and the abdominal process of females were used to evaluate the effects of chemical exposure on the development of these sex characteristics during maturation. Exposure of female daphnids to the nonsteroidal vertebrate estrogen diethylstilbesterol and the insect juvenile hormone analog methoprene at concentrations as low as 3.0 and 0.080 uM, respectively, stimulated development of the abdominal process. Exposure of males to the steroidal vertebrate androgen androstenedione (> or = 6.0 uM) stimulated development of the first antennae. These results demonstrate that the development of secondary sex characteristics in daphnids can be altered by chemical exposure.

Breast development (in men), behavioral changes, heart disease, male pattern baldness and depression. Side effects for women include a deepening and they may grow facial hair. In children or fetuses high levels of androstenedione (CAH) can lead to a number of changes. Females with congenital adrenal hyperplasia are born with an enlarged clitoris and normal internal reproductive tract structures. Males have normal genitals at birth. CAH causes abnormal growth for both sexes; patients will be tall as children and short as adults. Females develop male characteristics, and males experience premature sexual development.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of July 27, 2017: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for androstenedione is available.[Available from, as of April 24, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

Sampling at drinking water treatment plants in France during 2007-2008 detected androstenedione at concentrations of 0.1-2.1 ng/L in the influent waters (surface waters) and not detectable (0.04 ng/L)-2.8 ng/L in the effluent drinking water(1). Androstenedione was detected in STP (sewage treatment plant) effluents sampled from Beijing, China in 2006(2) and in 2008(3).

The Koc of androstenedione has been measured as log 3.79 (Koc of 6170) in Drummer soil, a silty clay sand soil, organic content of 2.91%(1). According to a classification scheme(2), this Koc value suggests that androstenedione is expected to be immobile in soil.

Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Anabolic Steroids. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation containing any quantity of the following substances, including its salts, esters and ethers. Anabolic steroids /including 4-androstenedione/, DEA Code 4000, is included on this list.

Androstenedione is a steroid hormone that is produced primarily in the adrenals, testes, and ovaries. It is classified as a weak androgen because it binds to the body's receptor for androgen hormones in a much less potent fashion than classic anabolic/androgenic steroids such as testosterone. It is synthesized from the precursor hormone dehydroepiandrosterone (DHEA) and is the direct precursor to testosterone. In normal physiologic circumstances, androstenedione can also be converted to potent feminizing hormones such as estrone and estradiol (both members of the estrogen class of hormones). ... Importantly, the enzymes that convert androstenedione to potent hormones like testosterone and estradiol are active not only in endocrine glands, but also in many peripheral body tissue such as muscle, bone, liver and brain.

4-androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.

Anabolic steroids reverses catabolic processes and negative nitrogen balance by promoting protein anabolism and stimulating appetite if there is concurrently a proper intake of calories and proteins. /Anabolic Steroids/

A comparative study was performed to assess the metabolism of the androgen precursor androstenedione (AD) in two gastropod species from the Muricidae family: Bolinus brandaris and Hexaplex trunculus. AD was mainly converted to 5alpha-dihydrotestosterone by microsomal fractions isolated from Bolinus brandaris, whereas it was primarily metabolized to testosterone by Hexaplex trunculus. Sex differences in the metabolism of AD were only detected in Bolinus brandaris and attributed to higher 5alpha-reductase activity in males. Thereafter, the effect of the organotin compounds, tributyltin (TBT) and triphenyltin (TPT), on the metabolism of AD was investigated. A significant interference was only detected in females, and differences between the modes of action of the two compounds were observed: TPT was a strong inhibitor of 5alpha-reductase activity in B. brandaris at a concentration as low as 100 nM whereas only TBT (10 uM) altered the metabolism of AD in H. trunculus by increasing the activity 17beta-hydroxysteroid dehydrogenase (17beta-HSD). Thus, this work shows that the metabolism of the androgen precursor AD strongly differs among gastropod species, both in terms of activity and metabolic profile, and further demonstrates the ability of TBT and TPT to interfere with key enzymatic pathways involved in androgen synthesis.

Bone is a target organ of androgens. The mechanism by which these steroids exert their action within bone cells is still poorly understood. The metabolism of androstenedione, the major circulating androgen in women, was, therefore, assessed in osteoblast-like bone cells cultured from bone of 16 postmenopausal women (mean age, 69 yr; range, 56-80) and 3 elderly men (mean age, 71 yr; range, 69-73) undergoing total hip replacement. Each cell strain was incubated under standardized conditions with varying concentrations of [1,2,6,7- (3)H]androstenedione (0.05-5 uM). In every instance 5 alpha-reduced metabolites and 17 beta-hydroxysteroids were formed. There was no correlation between the volumetric density of the resected bone and androstenedione metabolism of the corresponding cultured bone cell strains. The apparent Km for the 5 alpha-reductase activity (sum of androstanedione and dihydrotestosterone) of all 19 cell strains was 0.7 +/- 0.1 uM (mean +/- SEM), and the apparent Km for 17 beta- hydroxysteroid dehydrogenase (sum of testosterone and dihydrotestosterone) was 2.3 +/- 0.8 uM (mean +/- SEM), values similar to those reported for other androgen target organs. Our results demonstrate that human osteoblast-like cells have the capacity to transform androstenedione into the more potent biological androgens testosterone and dihydrotestosterone. Since the Km values of both 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase exceed the serum androstenedione concentration, the formation of testosterone and dihydrotestosterone appears to be mainly a function of substrate availability.

Up-regulation of aromatase expression in endometrial cells disseminated into the peritoneal cavity may enhance their survival via local estrogen synthesis, which may lead to endometriosis. The factors that mediate induction of aromatase in the endometrium are not well defined, but increased expression of steroidogenic factor (SF)-1 may play a role. The objective of the study was to determine whether androstenedione (A4), the predominant sex steroid in peritoneal fluid, regulates endometrial aromatase expression. This was a cell/tissue culture study ... conducted at an academic center. Quantitative real-time PCR, HPLC, and chromatin immunoprecipitation were used in this study. Treatment of cultured human endometrial explants and stromal cells with A4 (10 nm) significantly up-regulated expression of aromatase mRNA transcripts containing exon IIa at their 5'-ends. In endometrial stromal cells and the human endometrial surface epithelial (HES) cell line, induction of aromatase mRNA by A4 was associated with increased expression of SF-1. In HES cells, tritiated A4 was metabolized to estradiol, testosterone (T), dihydrotestosterone, and androstanediol. Both estradiol and T, but not nonaromatizable androgens, up-regulated aromatase and SF-1 mRNA in HES cells. Chromatin immunoprecipitation revealed that A4 enhanced recruitment of SF-1 to its response element (-136 bp) upstream of CYP19 exon IIa. This, together with the findings that both estrogen receptor antagonist, ICI 182,780, and aromatase inhibitor, fadrozole, suppressed A4 and T induction of aromatase and SF-1 mRNA, indicates that the inductive effects of A4 and T are mediated by their conversion to estrogens. Exposure of endometrial cells to A4 may enhance CYP19 gene expression through its aromatization to estrogens.

Androstenedione is synthesized in the adrenal gland and gonads from dehydroepiandrosterone. It is metabolized by the enzyme 17 beta-hydroxy steroid dehydrogenase to testosterone, and by the aromatase enzyme complex to estrone. Estrone is metabolized to estradiol.

Androstenedione is distributed to various tissues of the body and is metabolized to testosterone and estrone. The amount of testosterone produced per given dose of androstenedione appears to vary. Typically, a greater increase in serum testosterone is found in women compared to men, following intake of oral androstenedione.

Androstenedione is a known human metabolite of testosterone.

Absorption of /orally administered androstenedione/ appears variable, but some absorption does occur. Androstenedione is distributed to various tissues of the body ... .

/MILK/ It is not known whether anabolic steroids are distributed into breast milk. Problems in humans have not been documented. Women who take anabolic steroids should not breast feed. /Anabolic Steroids/

Anabolic steroids /including 4-androstenedione (DEA Code Number: 4000) are Schedule III controlled substances.

Schedule III Controlled Substance: (A) The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II. (B) The drug or other substance has a currently accepted medical use in treatment in the United States. (C) Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

MEDICATION

Androstanes, ie, pregnanes without the C-17 side chain, are important intermediates in the synthesis of progestins. One approach to the synthesis of androstanes is simply side-chain degradation of pregnanes. 16-Dehydropregnenolone acetate, an intermediate in the diosgenin to progesterone scheme, may be converted to androstenedione. 16-Dehydropregnenolone acetate is converted to its oxime. Treatment of the oxime with a Lewis acid induces a Beckmann rearrangement providing an enamide; hydrolysis and Oppenauer oxidation of the resulting alcohol forms androstenedione.

Many microorganisms have been found that partially or completely degrade cholesterol. Enzyme inhibitors or modified microbial agents have been used to control these degradations in order to form commercially useful steroidal intermediates. When mixed with metal ions (Ni, Co, Pb, or Se), chelating agents, or 8-hydroxyquinoline, various mycobacteria have been demonstrated to produce significant quantities of androsta-1,4-diene-3,17-dione from cholesterol. In a commercialized process for the microbial conversion of cholesterol to androsta-1,4-diene-3,17-dione, the 9a-hydroxylation step was inhibited by a,a-dipyridyl. In another commercial process, uv-generated mutations of Mycobacterium sp. have been used to produce androsta-4-ene-3,17-dione and androsta-1,4-diene-3,17-dione from beta-sitosterol.

Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-beta-CD to PS 1.92:1, 8.98 g/L PS, and at 120 hr of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process.

Androstenedione (Anabolic steroids (DEA Code Number 4000)) is a Schedule III controlled substance

Synthetic analogs of androgens have been used by professional, as well as amateur, athletes for possible performance enhancement.

Anabolic Steroid Control Act of 2004. Public Law 108-358 (October 22, 2004)... includes /androstenedione/ as an anabolic steroid