Dissociation of the Androgenic and Other Hormonal Activities from the Protein Anabolic Effects of Steroids

Potts, Gordon O.; Arnold, Aaron; Beyler, A. L.

doi:10.1007/978-3-642-66353-6_11

Cited by 16 publications

(15 citation statements)

References 83 publications

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“…Steroid replacement therapy by means of synthetically derived anabolic androgenic steroids (AAS) has been employed since the structure of testosterone was identified in 1935 2, 3. The limited oral bioavailability of testosterone4 as well as the need to differentiate desired anabolic from undesired androgenic effects5 and corresponding health issues6–8 has led to the production of thousands of potential AAS,9 but only a few have been introduced for pharmaceutical and medicinal applications. A major breakthrough in alternative medications was made in 1998, when the first nonsteroidal androgen receptor (AR) agonist was prepared 10.…”

Section: Introductionmentioning

confidence: 99%

Emerging drugs: mechanism of action, mass spectrometry and doping control analysis

et al. 2009

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The number of compounds and doping methods in sports is in a state of constant flux. In addition to 'traditional' doping agents, such as anabolic androgenic steroids or erythropoietin, new therapeutics and emerging drugs have considerable potential for misuse in elite sport. Such compounds are commonly based on new chemical structures, and the mechanisms underlying their modes of action represent new therapeutic approaches arising from recent advances in medical research; therefore, sports drug testing procedures need to be continuously modified and complementary methods developed, preferably based on mass spectrometry, to enable comprehensive doping controls. This tutorial not only discusses emerging drugs that can be categorized as anabolic agents (selective androgen receptor modulators, SARMs), gene doping [hypoxia-inducible factor stabilizers, peroxisome-proliferator-activated receptor (PPAR)delta-agonists] and erythropoietin-mimetics (Hematide) but also compounds with potentially performance-enhancing properties that are not classified in the current list of the World Anti-Doping Agency. Compounds such as ryanodine-calstabin-complex modulators (benzothiazepines) are included, their mass spectrometric properties discussed, and current approaches in sports drug testing outlined.

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Section: Introductionmentioning

confidence: 99%

Emerging drugs: mechanism of action, mass spectrometry and doping control analysis

et al. 2009

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“…below), the levator ani is not a typical skeletal muscle, and the validity of the assay has been seriously questioned (see Refs. 17,21,22). The rat levator ani muscle is in fact the dorsal bulbocavernosus muscle, which is peculiar to rodents, and which does not correspond to the levator ani muscle in man, cat, or dog (25).…”

mentioning

confidence: 96%

“…Refs. 17,21,22), e.g. comparing a myotrophic effect (weight increase of the levator ani muscle) with an androgenic effect (weight increase of accessory sex organs) in castrated male rats (23,24).…”

mentioning

confidence: 99%

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin*

1984

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It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. 1 alpha-Methyl-5 alpha-dihydrotestosterone (1 alpha-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [ RBAs relative to that of MT: MT greater than 19-nortestosterone ( NorT ; nandrolone) greater than methenolone (17 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3-one) greater than testosterone (T) greater than 1 alpha-methyl-DHT]. In other cases, AR binding was weak (RBA values less than 0.05): stanozolol (17 alpha-methyl-5 alpha- androstano [3,2-c]pyrazol-17 beta-ol), methanedienone (17 beta-hydroxy-17 alpha-methyl-1,4-androstadien-3-one), and fluoxymesterolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one) and ethylestrenol (17 alpha-ethyl-4- estren -17 beta-ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5 alpha-androstane-3 alpha, 17 beta-diol and its 3 beta-isomer (3 alpha- and 3 beta-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (1 alpha-methyl-DHT much greater than DHT greater than T greater than 3 beta-adiol greater than 3 alpha-adiol = 17 alpha-methyl-T greater than methenolone greater than methanedienone greater than stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The ideal AAS should have the anabolic effect of testosterone (or higher) without the andro genic effects, which are unwanted, especially for women and children [12,13]. Much effort has been made in order to separate the androgenic from the anabolic effects.…”

Section: Anabolic Steroids Designer Steroids Prohormones and Nutritiomentioning

confidence: 99%

“…Conse quently, MS instruments have been extensively used in doping control ana lysis for decades [6][7][8][9][10][11]. General structure for androgenic anabolic steroids indicating the nomenclature for carbon atoms and rings and structures of (B) testosterone and the designer steroids; (C) tetrahydrogestri-none [12]; (D) desoxymethyltestosterone [13,17]; (E) 1-methyltestosterone [18]; (F) 1-androsterone [19]; (G) 6-methyltestosterone [20] ; and (H) isoxazole [21]. The information about how these steroids were detected is included.…”

Section: Introductionmentioning

confidence: 99%

Current Status and Bioanalytical Challenges in The Detection of Unknown Anabolic Androgenic Steroids in Doping Control Analysis

et al. 2013

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Androgenic anabolic steroids (AAS) are prohibited in sports due to their anabolic effects. Doping control laboratories usually face the screening of AAS misuse by target methods based on MS detection. Although these methods allow for the sensitive and specific detection of targeted compounds and metabolites, the rest remain undetectable. This fact opens a door for cheaters, since different AAS can be synthesized in order to evade doping control tests. This situation was evidenced in 2003 with the discovery of the designer steroid tetrahydrogestrinone. One decade after this discovery, the detection of unknown AAS still remains one of the main analytical challenges in the doping control field. In this manuscript, the current situation in the detection of unknown AAS is reviewed. Although important steps have been made in order to minimize this analytical problem and different analytical strategies have been proposed, there are still some drawbacks related to each approach.

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Dissociation of the Androgenic and Other Hormonal Activities from the Protein Anabolic Effects of Steroids

Cited by 16 publications

References 83 publications

Emerging drugs: mechanism of action, mass spectrometry and doping control analysis

Emerging drugs: mechanism of action, mass spectrometry and doping control analysis

Relative Binding Affinity of Anabolic-Androgenic Steroids: Comparison of the Binding to the Androgen Receptors in Skeletal Muscle and in Prostate, as well as to Sex Hormone-Binding Globulin*

Current Status and Bioanalytical Challenges in The Detection of Unknown Anabolic Androgenic Steroids in Doping Control Analysis

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