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Molecules (Basel, Switzerland) Oct 2021Androstenedione is a steroidal hormone produced in male and female gonads, as well as in the adrenal glands, and it is known for its key role in the production of... (Review)
Review
Androstenedione is a steroidal hormone produced in male and female gonads, as well as in the adrenal glands, and it is known for its key role in the production of estrogen and testosterone. Androstenedione is also sold as an oral supplement, that is being utilized to increase testosterone levels. Simply known as "andro" by athletes, it is commonly touted as a natural alternative to anabolic steroids. By boosting testosterone levels, it is thought to be an enhancer for athletic performance, build body muscles, reduce fats, increase energy, maintain healthy RBCs, and increase sexual performance. Nevertheless, several of these effects are not yet scientifically proven. Though commonly used as a supplement for body building, it is listed among performance-enhancing drugs (PEDs) which is banned by the World Anti-Doping Agency, as well as the International Olympic Committee. This review focuses on the action mechanism behind androstenedione's health effects, and further side effects including clinical features, populations at risk, pharmacokinetics, metabolism, and toxicokinetics. A review of androstenedione regulation in drug doping is also presented.
Topics: Anabolic Agents; Androstenedione; Animals; Athletes; Athletic Performance; Dietary Supplements; Doping in Sports; Female; Humans; Male; Sex Factors; Testosterone
PubMed: 34684800
DOI: 10.3390/molecules26206210 -
Nihon Rinsho. Japanese Journal of... Mar 1995
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Bioresource Technology Oct 2008Androstenedione is a key intermediate of microbial steroid metabolism. It belongs to the 17-keto steroid family and is used as starting material for the preparation of... (Review)
Review
Androstenedione is a key intermediate of microbial steroid metabolism. It belongs to the 17-keto steroid family and is used as starting material for the preparation of different steroids. Androstenedione can be produced by microbial side chain cleavage of phytosterol, which is an alternative to multi-step chemical synthesis. In this review, various methods of biotransformation of sterols to androstenedione are surveyed. It begins with the history and current research status in this field. The existing methods of chemical and biochemical synthesis are examined. Various issues related to these methods and how researchers have addressed them is presented. Among these, the low solubility of sterols in aqueous systems is a critical problem since it limits the product yield. The main content of this review focuses on new methods of biotransformation that are being investigated. Recent biotechnological advances in this field are presented. The review ends with a note on future perspectives.
Topics: Androstenedione; Biotransformation; Phytosterols
PubMed: 18329874
DOI: 10.1016/j.biortech.2008.01.039 -
Acta Crystallographica. Section C,... Apr 2010The title compound, C(19)H(26)O(2), a B-norandrogen with a 6beta-methyl group, is a recently identified and experimentally tested potent new aromatase inhibitor. It...
The title compound, C(19)H(26)O(2), a B-norandrogen with a 6beta-methyl group, is a recently identified and experimentally tested potent new aromatase inhibitor. It shares structural and physicochemical similarities both with the natural substrate of the enzyme, androstenedione, and with exemestane, another potent aromatase inhibitor having a 6-methylidene group. X-ray diffraction results indicate that the B-nor molecule and exemestane have nearly the same oxygen-oxygen and methyl-methyl separations, though they have distinct configurations of the hydrophobic groups at the 6-position. These structural comparisons allow correlations to be inferred between the active site geometry of the molecules and the aromatase inhibition power of the studied compound.
Topics: Androstadienes; Androstenedione; Aromatase Inhibitors; Binding Sites; Catalysis; Crystallography, X-Ray; Molecular Structure; Norsteroids; Protein Binding; X-Ray Diffraction
PubMed: 20354306
DOI: 10.1107/S0108270110005871 -
Phytochemistry Jan 2020Filamentous fungi is a huge phylum of lower eukaryotes with diverse activities towards various substrates, however, their biocatalytic potential towards steroids remains...
Filamentous fungi is a huge phylum of lower eukaryotes with diverse activities towards various substrates, however, their biocatalytic potential towards steroids remains greatly underestimated. In this study, more than forty Ascomycota and Zygomycota fungal strains of 23 different genera were screened for the ability to catalyze structural modifications of 3-oxo-androstane steroids, - androst-4-ene-3,17-dione (AD) and androsta-1,4-diene-3,17-dione (ADD). Previously unexplored for these purposes strains of Absidia, Acremonium, Beauveria, Cunninghamella, Doratomyces, Drechslera, Fusarium, Gibberella genera were revealed capable of producing in a good yield valuable 7α-, 7β-, 11α- and 14α-hydroxylated derivatives, as well as 17β-reduced and 1(2)-dehydrogenated androstanes. The bioconversion routes of AD and ADD were proposed based on the key intermediates identification and time courses of the bioprocesses. Six ascomycete strains were discovered to provide effective 7β-hydroxylation of ADD which has not been so far reported. The structures of major products and intermediates were confirmed by HPLC, mass-spectrometry (MS), H and C NMR analyses. The results contribute to the knowledge on the functional diversity of steroid-transforming filamentous fungi. Previously unexplored fungal biocatalysts capable of effective performing structural modification of AD and ADD can be applied for industrial bioprocesses of new generation.
Topics: Androstadienes; Androstenedione; Biotransformation; Fungi; Molecular Conformation
PubMed: 31600654
DOI: 10.1016/j.phytochem.2019.112160 -
Methods in Molecular Biology (Clifton,... 2017The chapter describes the bioconversion of phytosterols to androstenedione (AD) with Mycobacterium spp. in shake flasks and fermenters, as well as LC-MS based methods...
The chapter describes the bioconversion of phytosterols to androstenedione (AD) with Mycobacterium spp. in shake flasks and fermenters, as well as LC-MS based methods for analysis of phytosterols and steroid products.Phytosterols are derived as a by-product of vegetable oil refining and of manufacture of wood pulp. Phytosterols contain the same four-ring nucleus as steroids, and may be converted to high-value steroids by removing the side chain at C17 and minor changes at other sites in the ring structure.Many bacteria, including Mycobacterium spp., are able to degrade phytosterols. Mutants of Mycobacterium spp. unable of ring cleavage can, when growing on phytosterols, accumulate the steroid intermediates androstenedione (AD) and/or androstadienedione (ADD).The practical challenge with microbial conversion of phytosterols to steroids is that both the substrate and the product are virtually insoluble in water. In addition, some steroids, notably ADD, may be toxic to cells.Two main strategies have been employed to overcome this challenge: the use of two-phase systems, and the addition of chemically modified cyclodextrins. The latter method is used here.Defined cultivation and bioconversion media for both shake flask and fermenter are given, as well as suggestions to minimize the practical problems caused by the water-insoluble phytosterol. Sampling, sample extraction, and quantification of substrates and products using LC-MS analysis are described.
Topics: Androstenedione; Chromatography, Liquid; Fermentation; Mycobacterium; Phytosterols; Plant Oils; Tandem Mass Spectrometry
PubMed: 28710629
DOI: 10.1007/978-1-4939-7183-1_13 -
JAMA Jun 1999
Topics: Androstenedione; Dietary Supplements; Drug and Narcotic Control; Humans; Nonprescription Drugs; Sports; United States
PubMed: 10359395
DOI: 10.1001/jama.281.21.2043 -
ACS Synthetic Biology Mar 2023Substrate competition within a metabolic network constitutes a common challenge in microbial biosynthesis system engineering, especially if indispensable enzymes can...
Substrate competition within a metabolic network constitutes a common challenge in microbial biosynthesis system engineering, especially if indispensable enzymes can produce multiple intermediates from a single substrate. Androstenedione (4AD) is a central intermediate in the production of a series of steroidal pharmaceuticals; however, its yield via the coexpression of 3β-hydroxysteroid dehydrogenase (β) and 17α-hydroxylase/17,20-lyase () in a microbial chassis affords a nonlinear pathway in which these enzymes compete for substrates and produce structurally similar unwanted intermediates, thereby reducing 4AD yields. To avoid substrate competition, we split the competing β and pathway components into two separate strains to linearize the pathway. This spatial segregation increased substrate availability for β in the upstream strain, consequently decreasing the accumulation of the unwanted intermediate 17-hydroxypregnenolone (17OHP5) from 94.8 ± 4.4% in single-chassis monocultures to 24.8 ± 12.6% in cocultures of strains expressing β and separately. Orthologue screening to increase catalytic efficiency and the preferential production of desired intermediates increased the biotransformation capacity in the downstream pathway, further decreasing 17OHP5 accumulation to 3.9%. Furthermore, nitrogen limitation induced early 4AD accumulation (final titer, 7.71 mg/L). This study provides a framework for reducing intrapathway competition between essential enzymes during natural product biosynthesis as well as a proof-of-concept platform for linear steroid production.
Topics: Androstenedione; Coculture Techniques; Metabolic Networks and Pathways
PubMed: 36857753
DOI: 10.1021/acssynbio.2c00590 -
Methods in Molecular Biology (Clifton,... 2017Phytosterols, generated as a by-product of vegetable oils or wood pulp, contain the cyclopentane-perhydro-phenanthrene nucleus, and can be converted into steroid...
Phytosterols, generated as a by-product of vegetable oils or wood pulp, contain the cyclopentane-perhydro-phenanthrene nucleus, and can be converted into steroid intermediates by removing the C17 side chain. This chapter shows the scale-up, from flask to fermentor, of the phytosterols bioconversion into 4-androstene-3,17-dione (androstenedione; AD) with Mycobacterium neoaurum B-3805. Due to the fact that phytosterols and AD are nearly insoluble in water, two-phase systems and the use of chemically modified cyclodextrins have been described as methods to solve it. Here we use a water-oil two-phase system that allows for the bioconversion of up to 20 g/L of phytosterols into AD in 20 L fermentor.
Topics: Androstenedione; Biotransformation; Mycobacterium; Phytosterols; Plant Oils; Glycine max; Water
PubMed: 28710630
DOI: 10.1007/978-1-4939-7183-1_14 -
The Aging Male : the Official Journal... Sep 2016The purpose of the study was to examine the effects of acute androstenedione supplementation on hormone levels in older men at rest and during exercise. Men (n = 11)... (Randomized Controlled Trial)
Randomized Controlled Trial
The purpose of the study was to examine the effects of acute androstenedione supplementation on hormone levels in older men at rest and during exercise. Men (n = 11) between the ages of 58 and 69 were divided into an experimental (n = 6; 62.33 ± 2.57 y) and control (n = 5; 60.2 ± 1.02 y) groups. Each participant received an oral 300 mg dose of either androstenedione (experimental) or a cellulose placebo (control) for 7 d. Pre- and post-supplementation participants completed two separate, 20-min strength tasks consisting of leg extension and leg curls at different percentages of their 10-RM. Researchers collected blood samples pre-, during, and post-exercise. Blood samples were analyzed for testosterone, androstenedione, and estradiol levels. The researchers found a significant difference between pre- (4.36 ± 56 ng/mL) and post- (5.51 ± 0.35 ng/mL) testosterone levels, as well as pre- (0.88 ± 0.20) and post- (7.46 ± 1.25) androstenedione levels, but no significant differences between pre- and post-estradiol levels for either group. It appears that short-term androstenedione supplementation augmented acute testosterone responses to resistance exercise in older men. However, further study of this supplement is needed to determine any potential it may have in mitigating andropause.
Topics: Aged; Androstenedione; Dietary Supplements; Exercise; Humans; Male; Middle Aged; Testosterone
PubMed: 27558186
DOI: 10.3109/13685538.2016.1167180