Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs
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{"title"=>"Advantages and limitations of androgen receptor-based methods for detecting anabolic androgenic steroid abuse as performance enhancing drugs", "type"=>"journal", "authors"=>[{"first_name"=>"Kathy", "last_name"=>"Bailey", "scopus_author_id"=>"57188698749"}, {"first_name"=>"Tahmineh", "last_name"=>"Yazdi", "scopus_author_id"=>"57188702926"}, {"first_name"=>"Umesh", "last_name"=>"Masharani", "scopus_author_id"=>"6601986523"}, {"first_name"=>"Blake", "last_name"=>"Tyrrell", "scopus_author_id"=>"57188707730"}, {"first_name"=>"Anthony", "last_name"=>"Butch", "scopus_author_id"=>"7003694856"}, {"first_name"=>"Fred", "last_name"=>"Schaufele", "scopus_author_id"=>"7004111723"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"26998755", "sgr"=>"84962429259", "doi"=>"10.1371/journal.pone.0151860", "scopus"=>"2-s2.0-84962429259", "pui"=>"609296668", "issn"=>"19326203"}, "id"=>"f6badb06-e7a4-38b7-8f06-3f751c6c9856", "abstract"=>"Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T-equivalent' concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact.", "link"=>"http://www.mendeley.com/research/advantages-limitations-androgen-receptorbased-methods-detecting-anabolic-androgenic-steroid-abuse-pe", "reader_count"=>23, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Student > Doctoral Student"=>3, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>8, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Student > Doctoral Student"=>3, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>8, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>2, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Business, Management and Accounting"=>1, "Sports and Recreations"=>2, "Chemical Engineering"=>1, "Chemistry"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>2}, "Sports and Recreations"=>{"Sports and Recreations"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4865614"], "description"=>"<p><b>A,</b> Fluorescence microscopy images of YFP-tagged AR and mCherry-NLS-mCherry nuclear marker expressed in the reporter cells grown in androgen-depleted cell culture media (upper panels). Incubation with an androgen redistributes the AR to the cell nucleus (lower panels). <b>B,</b> AR BioAssay standard curve: the concentration of T in the media dictates the level of ‘green’ fluorescence of YFP-tagged AR in image regions defined by red fluorescence emitted from mCherry FP-marked cell nuclei change. Maximum AR-YFP nuclear fluorescence is set as 100% and minimum is set as 0%. The nuclear AR level following incubation with a glucuronidase-treated urine sample defines the amounts of androgens present in the well (blue lines), which then is corrected for the urine dilution into the cell culture media to obtain the ‘T-equivalent’ concentration of urinary androgens present.</p>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127171, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151860.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/AR_BioAssay_for_androgens_/3127171", "title"=>"AR BioAssay for androgens.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-03-21 05:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/4865788"], "description"=>"<p><b>Efficacy of A, natural steroids and B, AASs on the AR BioAssay.</b> Maximal AR BioAssay activity was determined from dose response curves (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151860#pone.0151860.g002\" target=\"_blank\">Fig 2</a>). The compounds that achieved a maximal level of BioAssay activity at highest concentrations studied (10<sup>-6</sup>M) are shown in blue; steroids with efficacies comparable to testosterone (100% efficacy) are shown in dark blue. Those with lower efficacies are shown in light blue. Those compounds not achieving a maximum level of BioAssay activity are shown in grey. The mean ± sd for each compound were averaged from the number of independent dose response studies shown (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151860#pone.0151860.s001\" target=\"_blank\">S1 Fig</a>, which also includes the names and chemical structures of the compounds). In A, compounds are grouped according to global structural similarities to androgens (A), progestagens (P), corticosteroids (C) and estrogens (E).</p>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127270, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151860.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Advantages_and_Limitations_of_Androgen_Receptor_Based_Methods_for_Detecting_Anabolic_Androgenic_Steroid_Abuse_as_Performance_Enhancing_Drugs_Fig_4/3127270", "title"=>"Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs - Fig 4", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-03-21 05:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/4865683"], "description"=>"<p>AR BioAssay reporter cells were grown in 39.5 μl androgen-depleted culture media and 0.5 μl of glucuronidase-treated urine. The AR-YFP fluorescence level activated by androgens in the urine was compared against the T standard curve to extrapolate androgen concentration in T-equivalent activity levels. That concentration was multiplied by the 80-fold dilution of the urine in the cell culture media. These urine androgen levels (x-axis) then were compared to T measurements conducted by MS on the same samples (y-axis). For T-supplemented individuals, linear regression would be hypothesized to show equivalency (slope = 1.0) of androgen and T levels.</p>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127207, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151860.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Equivalency_of_androgen_AR_BioAssay_and_T_MS_measurements_in_urine_of_T_treated_patients_/3127207", "title"=>"Equivalency of androgen (AR BioAssay) and T (MS) measurements in urine of T-treated patients.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-03-21 05:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/4865830"], "description"=>"<p><b>Potency (Log EC50) of A, natural steroids and B, AASs in the AR BioAssay.</b> Potency can be established only for compounds that reached maximal activity at the highest concentrations investigated (10<sup>-6</sup>M). The more negative a Log EC50, the lower the concentration of compound required to reach half-maximal activity (i.e. higher potency). Many of the AAS’s have a higher potency than testosterone. Note that designer AAS’s, such as tetrahydrogestrinone (‘the clear’) are detected in this assay with an efficacy similar to DHT. See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151860#pone.0151860.g004\" target=\"_blank\">Fig 4</a> for description of symbols and procedures.</p>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127303, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151860.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Advantages_and_Limitations_of_Androgen_Receptor_Based_Methods_for_Detecting_Anabolic_Androgenic_Steroid_Abuse_as_Performance_Enhancing_Drugs_Fig_5/3127303", "title"=>"Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs - Fig 5", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-03-21 05:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/4865911"], "description"=>"<p>Compounds showing any activity are in Bold. Detection limit is set to be AR nuclear fluorescence level of 10% the maximum of the T curve with a dilution of 1 μl of urine into 40 μl of total assay volume. Chemical structures and # of independent studies conducted for each compound are listed in S1 Fig.</p>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127372, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151860.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/AR_BioAssay_detection_limits_for_each_compound_in_urine_/3127372", "title"=>"AR BioAssay detection limits for each compound in urine.", "pos_in_sequence"=>8, "defined_type"=>3, "published_date"=>"2016-03-21 05:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/4865887"], "description"=>"<p><b>A, Efficacy and B, Potency of AAS metabolites.</b> The metabolites (white bars; e.g. m27) are shown relative to the AASs from which they are metabolized in the body (black bars; e.g. AAS27). See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151860#pone.0151860.g004\" target=\"_blank\">Fig 4</a> for description of symbols and procedures.</p>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127348, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151860.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Advantages_and_Limitations_of_Androgen_Receptor_Based_Methods_for_Detecting_Anabolic_Androgenic_Steroid_Abuse_as_Performance_Enhancing_Drugs_Fig_6/3127348", "title"=>"Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs - Fig 6", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-03-21 05:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/4865470", "https://ndownloader.figshare.com/files/4865485", "https://ndownloader.figshare.com/files/4865491", "https://ndownloader.figshare.com/files/4865509", "https://ndownloader.figshare.com/files/4865521", "https://ndownloader.figshare.com/files/4865536"], "description"=>"<div><p>Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete’s urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as ‘T-equivalent’ concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact.</p></div>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127099, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0151860.s001", "https://dx.doi.org/10.1371/journal.pone.0151860.s002", "https://dx.doi.org/10.1371/journal.pone.0151860.s003", "https://dx.doi.org/10.1371/journal.pone.0151860.s004", "https://dx.doi.org/10.1371/journal.pone.0151860.s005", "https://dx.doi.org/10.1371/journal.pone.0151860.s006"], "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Advantages_and_Limitations_of_Androgen_Receptor_Based_Methods_for_Detecting_Anabolic_Androgenic_Steroid_Abuse_as_Performance_Enhancing_Drugs/3127099", "title"=>"Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-03-21 05:20:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/4865734"], "description"=>"<p>Androgen levels measured by AR BioAssay (solid line) and T levels measured by MS in glucuronidase-treated urine from two hypogonadal patients (<b>A</b> and <b>B</b>) pre- and post-T injection (arrows). Samples were collected and stored at home and returned at the next physician visit.</p>", "links"=>[], "tags"=>["urine", "AR BioAssay activity", "doping control programs use mass spectrometry", "Performance Enhancing Drugs Testosterone", "Anabolic Androgenic Steroid Abuse", "androgen", "MS", "PED", "AR BioAssay activity levels", "T dose response curve", "UCLA", "AAS", "AR BioAssay"], "article_id"=>3127231, "categories"=>["Biochemistry", "Medicine", "Genetics", "Physiology", "Pharmacology", "Biotechnology", "Environmental Sciences not elsewhere classified", "Chemical Sciences not elsewhere classified", "Science Policy", "Sociology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Kathy Bailey", "Tahmineh Yazdi", "Umesh Masharani", "Blake Tyrrell", "Anthony Butch", "Fred Schaufele"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151860.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Rise_and_fall_in_urine_androgens_following_injection_with_T_/3127231", "title"=>"Rise and fall in urine androgens following injection with T.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-03-21 05:20:35"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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