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Sample records for steroid androgens deconjugation

  1. Optimised deconjugation of androgenic steroid conjugates in bovine urine

    DEFF Research Database (Denmark)

    Pedersen, Mikael; Frandsen, Henrik Lauritz; Andersen, Jens Hinge

    2017-01-01

    and glucuronidase resulting in free steroids in the extract. It is well known that some sulphates are not deconjugated using aryl sulphatase; instead, for example, solvolysis can be used for deconjugation of these aliphatic sulphates. The effectiveness of solvolysis on androgenic steroid sulphates was tested......After administration of steroids to animals the steroids are partially metabolised in the liver and kidney to phase 2 metabolites, i.e., glucuronic acid or sulphate conjugates. During analysis these conjugated metabolites are normally deconjugated enzymatically with aryl sulphatase...... with selected aliphatic steroid sulphates (boldenone sulphate, nortestosteron sulphate and testosterone sulphate), and the method was validated for analysis of androgenic steroids in bovine urine using free steroids, steroid sulphates and steroid glucuronides as standards. Glucuronidase and sulphuric acid...

  2. Hypochlorite Oxidation of Select Androgenic Steroids

    Science.gov (United States)

    Steroid hormones are vital for regulation of various biological functions including sexual development. Elevated concentrations of natural and synthetic androgenic steroids have been shown to adversely affect normal development in indigenous aqueous species. Androgens and their s...

  3. ABUSE OF ANABOLIC ANDROGENIC STEROIDS

    Directory of Open Access Journals (Sweden)

    Abbas Yavari

    2009-09-01

    Full Text Available According to the International Olympic Committee, the abuse of anabolic androgenic steroids (AASS is found in over 50% of positive doping tests. AASS abuse is not restricted to the organized sports andwidespread use. It remains as an unsolved public-health problem.Lower black market price, easier access to AASS, bodybuilding clubs and internet advertising are factors of this increasingly misuse. There is not real data about the prevalence of AASS abuse in various populations or countries, because most of athletes or students, due to their prohibition or ethical aspects do not admit to AASS abuse. Often they are aware of the risks of their choice and yet, are eager to put themselves at risk without deeper consideration. The abusers use them to improve their physical fitness and appearance.Present article has been collected to elucidate the risks and adverse effects of AASS and explanation of mechanisms of these events.

  4. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, Andrea; Iaquinto, Gaetano; Gluud, Christian

    2002-01-01

    The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease.......The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease....

  5. Androgenic anabolic steroids also impair right ventricular function.

    Science.gov (United States)

    Kasikcioglu, Erdem; Oflaz, Huseyin; Umman, Berrin; Bugra, Zehra

    2009-05-01

    Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

  6. Review of Androgenic Anabolic Steroid Use

    Energy Technology Data Exchange (ETDEWEB)

    T. Borges; G. Eisele; C. Byrd

    2001-07-31

    An area that has been overlooked within personnel security evaluations is employee use of androgenic-anabolic steroids (AAS). Current drug testing within the federal government does not include testing for anabolic steroids, and the difficulties to implement such testing protocols-not to mention the cost involved-make AAS testing highly improbable. The basis of this report is to bring to the forefront the damage that anabolic steroids can cause from both a physical and a psychological standpoint. Most individuals who use AASs do so to increase their muscle mass because they wish to gain some type of competitive edge during athletic competition or they wish to enhance their physical features for self-satisfaction and self-esteem (i.e., body building). Security officers are one group of men who often take high doses of anabolic steroids, according to the Second Report of the Senate Standing Committee (1990). The negative psychological characteristics for AAS use is extensive and includes prominent hostility, aggressiveness, irritability, euphoria, grandiose beliefs, hyperactivity, reckless behavior, increased sexual appetite, unpredictability, poor impulse control, mood fluctuations, and insomnia. The drug may invoke a sense of power and invincibility (Leckman and Scahill, 1990). Depressive symptoms, such as anhedonia, fatigue, impaired concentration, decreased libido, and even suicidality (Pope and Katz, 1992) have been noted with steroid withdrawal. It appears that long-term users of AAS experience similar characteristics as other substance abusers (i.e., craving, dependence, and withdrawal symptoms).

  7. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2006-01-01

    Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  8. Hypercholesterolemia in Male Power Lifters Using Anabolic-Androgenic Steroids.

    Science.gov (United States)

    Cohen, Jonathan C.; And Others

    1988-01-01

    Measurement of serum cholesterol concentrations in male power lifters who used anabolic-androgenic steroids for eight weeks, three years, or eight years indicated that mean serum cholesterol levels increased with drug use, but decreased promptly to near pre-steroid levels after steroid use ended. (Author/CB)

  9. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure.

    Science.gov (United States)

    Fragkaki, A G; Angelis, Y S; Koupparis, M; Tsantili-Kakoulidou, A; Kokotos, G; Georgakopoulos, C

    2009-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

  10. Multiple arterial thromboses associated with anabolic androgenic steroids.

    Science.gov (United States)

    McCulloch, Neil Arthur; Abbas, Jonathan Raihan; Simms, Malcolm Harold

    2014-03-01

    The use of supraphysiological doses of anabolic androgenic steroids can have serious side effects. This article reports the case of a young man who suffered potentially life-threatening arterial thromboses following the use of these drugs.

  11. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Iaquinto, G; Gluud, C

    2003-01-01

    Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  12. ANABOLIC ANDROGENIC STEROIDS AND ADVERSE EVENTS OF THEIR APPLICATION

    Directory of Open Access Journals (Sweden)

    Nina Đukanović

    2011-08-01

    Full Text Available Anabolic androgenic steroids are synthetic compounds originating from testosterone. Their main effects are the control of development and expression of male secondary sexual characteristics, which are known as androgenic effects, and encourage muscle growth or anabolic effects. Anabolic androgenic steroids are most commonly used illegal substances. Besides these physiological effects, which are achieved using therapeutic doses of these preparations, higher doses than recommended, especially over the longer term, may be associated with the emergence of numerous adverse events. Adverse events may be registered in almost all organs and organ systems, but usually include changes in the reproductive system, skin, liver and cardiovascular system.

  13. Illicit Anabolic-Androgenic Steroid Use

    Science.gov (United States)

    Kanayama, Gen; Hudson, James I.; Pope, Harrison G.

    2009-01-01

    The anabolic-androgenic steroids (AAS) are a family of hormones that includes testosterone and its derivatives. These substances have been used by elite athletes since the 1950s, but they did not become widespread drugs of abuse in the general population until the 1980s. Thus, knowledge of the medical and behavioral effects of illicit AAS use is still evolving. Surveys suggest that many millions of boys and men, primarily in Western countries, have abused AAS to enhance athletic performance or personal appearance. AAS use among girls and women is much less common. Taken in supraphysiologic doses, AAS show various long-term adverse medical effects, especially cardiovascular toxicity. Behavioral effects of AAS include hypomanic or manic symptoms, sometimes accompanied by aggression or violence, which usually occur while taking AAS, and depressive symptoms occurring during AAS withdrawal. However, these symptoms are idiosyncratic and afflict only a minority of illicit users; the mechanism of these idiosyncratic responses remains unclear. AAS users may also ingest a range of other illicit drugs, including both “body-image” drugs to enhance physical appearance or performance, and classical drugs of abuse. In particular, AAS users appear particularly prone to opioid use. There may well be a biological basis for this association, since both human and animal data suggest that AAS and opioids may share similar brain mechanisms. Finally, AAS may cause a dependence syndrome in a substantial minority of users. AAS dependence may pose a growing public health problem in future years, but remains little studied. PMID:19769977

  14. Predictors of future anabolic androgenic steroid use.

    Science.gov (United States)

    Wichstrøm, Lars

    2006-09-01

    To prospectively study the stability of anabolic androgenic steroid (AAS) use and predictors of AAS use, and to investigate whether AAS use alters the risk of later emotional and behavioral problems. Survey of a national sample of Norwegian high school students (age 15-19) in 1994 followed up in 1999 (N = 2924). Measures of frequent alcohol intoxication (50+ times per 12 months), cannabis use (12 months), hard drug use (12 months), being offered cannabis, eating problems, conduct problems, sexual debut before age 15, BMI, involvement in power sports, perceived physical appearance, and satisfaction with body parts were obtained. Life-time prevalence of AAS use were 1.9 and 0.8% in the follow-up period. Multivariate logistic regression revealed that future AAS use was predicted by young age, male gender, previous AAS use, involvement in power sports, and frequent alcohol intoxication. AAS use did not predict future emotional or behavioral problems other than reducing the risk of future frequent alcohol intoxication. Frequent alcohol intoxication and involvement in power sports appear to predict future AAS use. At the population level there was little stability in individual AAS use from adolescence to early adulthood. No detrimental effects of AAS use could be detected in this study, but low statistical power limits this conclusion.

  15. The Central Effects of Androgenic-anabolic Steroid Use.

    Science.gov (United States)

    Mędraś, Marek; Brona, Anna; Jóźków, Paweł

    : Millions of men use androgenic-anabolic steroids (AAS) to stimulate muscle growth and improve physical appearance. Although 1 out of 3 people who uses androgenic-anabolic steroids develops a steroid use disorder, the effects of the drugs on the central nervous system and the psyche are still not well understood. Although most addictive substances improve mood immediately after administration, AAS exert less pronounced euphoric effects. Instead, they are primarily taken for the delayed gratification of increased muscle mass. Withdrawal from AAS may lead to a range of somatic and psychiatric symptoms, and, in many cases, comprehensive treatment supervised by an endocrinologist and a psychiatrist is required.

  16. Androgenic anabolic steroid use among male adolescents in Falkenberg.

    Science.gov (United States)

    Nilsson, S

    1995-01-01

    Recent reports show that androgenic anabolic steroids are used by many teenagers, not as a deliberate attempt to give them strength, better athletic performance, etc., but to improve their looks. The so-called macho cult among young boys tempts them into using androgenic anabolic steroids to give them bigger muscles and a more powerful appearance. This study was undertaken to investigate the prevalence of androgenic anabolic steroid use among teenagers in a small town and to create a platform for future work with the aim of decreasing the misuse of these drugs. In Falkenberg, a town in the county of Halland in the west of Sweden, the pupils at two high schools were investigated by means of an anonymous multiple-choice questionnaire. A total of 1383 students (688 males and 695 females) aged 14-19 years participated in the study, giving a participation rate of 96%. The number of answers completed was 99%. The use of androgenic anabolic steroids is a reality among male teenagers in Falkenberg, with 5.8% of them using the drugs. Among 15- to 16-year-old boys misuse of these drugs is as high as 10%, and of these 50% (5.0% of total) also inject ampoules of the drugs. This prevalence is alarming since the adverse effects of androgenic anabolic steroids are more serious in teenagers. Serious action must be taken to inform teenagers of the consequences of misusing drugs.

  17. Prevalence and awareness of anabolic androgenic steroid use ...

    African Journals Online (AJOL)

    Purpose: To examine the prevalence and awareness of anabolic-androgenic steroid (AAS) use among male bodybuilders visiting gyms in Jazan region, Saudi Arabia. Methods: A cross-sectional survey was conducted among 500 male bodybuilders visiting gyms in the Jazan region of Saudi Arabia. Information on ...

  18. Psychological and Behavioral Effects of Anabolic-Androgenic Steroids.

    Science.gov (United States)

    Bahrke, Michael S.

    This review of the literature on the psychological and behavioral effects of anabolic-androgenic steroids (AS) first looks at aspects of the history and prevalence of AS use in competitive sports. Research suggests that one-quarter to one-half million adolescents in the United States have used, or are currently using AS. Some effects of androgens…

  19. Procoagulant State in Current and Former Anabolic Androgenic Steroid Abusers

    DEFF Research Database (Denmark)

    Chang, Simon; Rasmussen, Jon J; Frandsen, Mikkel N

    2018-01-01

    BACKGROUND:  Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. METHODS:  Men 18 to 50 years of age were included...

  20. Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.

    Science.gov (United States)

    Thevis, Mario; Schänzer, Wilhelm

    2010-01-01

    The central role of testosterone in the development of male characteristics, as well as its beneficial effects on physical performance and muscle growth, has led to the search for synthetic alternatives with improved pharmacological profiles. Hundreds of steroidal analogs have been prepared with a superior oral bioavailability, which should also possess reduced undesirable effects. However, only a few entered the pharmaceutical market due to severe toxicological incidences that were mainly attributed to the lack of tissue selectivity. Prominent representatives of anabolic-androgenic steroids (AAS) are for instance methyltestosterone, metandienone and stanozolol, which are discussed as model compounds with regard to general pharmacological aspects of synthetic AAS. Recently, nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones. These so-called selective androgen receptor modulators (SARMs) are currently undergoing late clinical trials (IIb) and will be prohibited by the World Anti-Doping Agency from January 2008. Their entirely synthetic structures are barely related to steroids, but particular functional groups allow for the tissue-selective activation or inhibition of androgen receptors and, thus, the stimulation of muscle growth without the risk of severe undesirable effects commonly observed in steroid replacement therapies. Hence, these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.

  1. When color fails: illicit blue tablets containing anabolic androgen steroids.

    Science.gov (United States)

    Favretto, Donata; Castagna, Franca; Maietti, Sergio; Boscolo-Berto, Rafael; Ferrara, Santo Davide

    2013-09-01

    The necessity of specific, confirmatory tests in the identification of seized illicit products was highlighted by the analysis of eighteen heart shaped, blue tablets confiscated by Police at a street control in the North East of Italy. The tablets responded as amphetamines to a preliminary color test (Marquis); a subsequent, confirmatory assay by gas chromatography-mass spectrometry revealed the presence of two anabolic androgen steroids (AAS), methandienone and methyltestosterone, in concentration of 1.7 and 1.5mg respectively per tablet; no trace of amphetamine-like or nitrogen containing compounds was found. The observed orange coloration was due to the reaction of concentrated sulphuric acid, contained in the Marquis reagent, with the Δ(4) C-3 keto group of steroids. The two AAS, banned under the world antidoping code, are not considered as psychoactive drugs of abuse in most countries, although their trafficking may entangle severe public health concerns. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Screening hybridomas for anabolic androgenic steroids by steroid analog antigen microarray.

    Science.gov (United States)

    Du, Hongwu; Chen, Guangyu; Bian, Yongzhong; Xing, Cenzan; Ding, Xue; Zhu, Mengliang; Xun, Yiping; Chen, Peng; Zhou, Yabin; Li, Shaoxu

    2015-01-01

    Currently, dozens of anabolic androgenic steroids (AAS) are forbidden in the World Anti-Doping Agency Prohibited List, however, despite extensive investigation, there are still lots of AAS without corresponding monoclonal antibodies. A steroid analog antigen microarray made up of ten AAS was fabricated to screen the hybridoma and it was found an original unsuccessful clone turned out to be a candidate anti-boldenone antibody, without any cross-reactions with endogenous AAS or 44 different AAS standard reference materials tested. Our findings suggested that steroid analog antigen microarray could be a promising tool to screen and characterize new applications of antibodies for structure analogs, and this also exhibits the potential to fast identify effective epitopes of hybridomas in a single assay.

  3. A new dawn for androgens: Novel lessons from 11-oxygenated C19 steroids.

    Science.gov (United States)

    Pretorius, Elzette; Arlt, Wiebke; Storbeck, Karl-Heinz

    2017-02-05

    The abundant adrenal C19 steroid 11β-hydroxyandrostenedione (11OHA4) has been written off as a dead-end product of adrenal steroidogenesis. However, recent evidence has demonstrated that 11OHA4 is the precursor to the potent androgenic 11-oxygenated steroids, 11-ketotestosterone and 11-ketodihydrotestosterone, that bind and activate the human androgen receptor similarly to testosterone and DHT. The significance of this discovery becomes apparent when considering androgen dependent diseases such as castration resistant prostate cancer and diseases associated with androgen excess, e.g. congenital adrenal hyperplasia and polycystic ovary syndrome. In this review we describe the production and metabolism of 11-oxygenated steroids. We subsequently discuss their androgenic activity and highlight the putative role of these androgens in disease states. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Anabolic-Androgenic Steroid Use Among 1,010 College Men.

    Science.gov (United States)

    Pope, Harrison G., Jr.; And Others

    1988-01-01

    Two percent of 1,010 male college students responding to a questionnaire about anabolic-androgenic steroid use reported using steroids; most of the users were competitive athletes, although some used steroids to improve their physical appearance. Users were not distinguished from non-users in terms of academic achievement or use of other illicit…

  5. Anabolic-Androgenic Steroids: Prevalence, Knowledge, and Attitudes in Junior and Senior High School Students.

    Science.gov (United States)

    Luetkemeier, Maurie J.; And Others

    1995-01-01

    Reports a survey of junior and senior high school students that investigated the prevalence of anabolic-androgenic steroid use and examined gender, sports participation, and illicit drug use. Results indicated the prevalence of steroid use was 3.3%. Steroid use was greater for males, users of other drugs, and strength trainers. (SM)

  6. National Athletic Trainers' Association Position Statement: Anabolic-Androgenic Steroids

    Science.gov (United States)

    Kersey, Robert D.; Elliot, Diane L.; Goldberg, Linn; Kanayama, Gen; Leone, James E.; Pavlovich, Mike; Pope, Harrison G.

    2012-01-01

    This NATA position statement was developed by the NATA Research & Education Foundation. Objective This manuscript summarizes the best available scholarly evidence related to anabolic-androgenic steroids (AAS) as a reference for health care professionals, including athletic trainers, educators, and interested others. Background Health care professionals associated with sports or exercise should understand and be prepared to educate others about AAS. These synthetic, testosterone-based derivatives are widely abused by athletes and nonathletes to gain athletic performance advantages, develop their physiques, and improve their body image. Although AAS can be ergogenic, their abuse may lead to numerous negative health effects. Recommendations Abusers of AAS often rely on questionable information sources. Sports medicine professionals can therefore serve an important role by providing accurate, reliable information. The recommendations provide health care professionals with a current and accurate synopsis of the AAS-related research. PMID:23068595

  7. The metabolism of anabolic-androgenic steroids in the greyhound.

    Science.gov (United States)

    McKinney, Andrew R; Cawley, Adam T; Young, E Bruce; Kerwick, Carmel M; Cunnington, Karen; Stewart, Rhiannon T; Ambrus, Joseph I; Willis, Anthony C; McLeod, Malcolm D

    2013-04-01

    Effective control of the use of anabolic-androgenic steroids (AASs) in animal sports is essential in order to ensure both animal welfare and integrity. In order to better police their use in Australian and New Zealand greyhound racing, thorough metabolic studies have been carried out on a range of registered human and veterinary AASs available in the region. Canine metabolic data are presented for the AASs boldenone, danazol, ethylestrenol, mesterolone, methandriol, nandrolone and norethandrolone. The principal Phase I metabolic processes observed were the reduction of A-ring unsaturations and/or 3-ketones with either 3α,5β- or 3β,5α-stereochemistry, the oxidation of secondary 17β-hydroxyl groups and 16α-hydroxylation. The Phase II β-glucuronylation of sterol metabolites was extensive. The presented data have enabled the effective analysis of AASs and their metabolites in competition greyhound urine samples.

  8. Characteristics and outcome of patients with heart failure due to anabolic-androgenic steroids

    DEFF Research Database (Denmark)

    Søndergaard, Eva Bjerre; Thune, Jens Jakob; Gustafsson, Finn

    2014-01-01

    OBJECTIVES: The objective of the study was to analyse the outcome of patients with advanced heart failure due to abuse of anabolic-androgenic steroids. DESIGN: A retrospective chart review of patients admitted or referred for advanced heart failure, due to anabolic-androgenic steroid abuse...... with angiotensin-converting enzyme inhibitors and beta-blockers. The remaining 3 patients required implantation of a LV assist device (LVAD) and were listed for heart transplantation. No recovery of LV function in the patients treated with assist device was seen. CONCLUSION: Anabolic-androgenic steroid...

  9. Brain connectivity aberrations in anabolic-androgenic steroid users

    Directory of Open Access Journals (Sweden)

    Lars T. Westlye

    2017-01-01

    Full Text Available Sustained anabolic-androgenic steroid (AAS use has adverse behavioral consequences, including aggression, violence and impulsivity. Candidate mechanisms include disruptions of brain networks with high concentrations of androgen receptors and critically involved in emotional and cognitive regulation. Here, we tested the effects of AAS on resting-state functional brain connectivity in the largest sample of AAS-users to date. We collected resting-state functional magnetic resonance imaging (fMRI data from 151 males engaged in heavy resistance strength training. 50 users tested positive for AAS based on the testosterone to epitestosterone (T/E ratio and doping substances in urine. 16 previous users and 59 controls tested negative. We estimated brain network nodes and their time-series using ICA and dual regression and defined connectivity matrices as the between-node partial correlations. In line with the emotional and behavioral consequences of AAS, current users exhibited reduced functional connectivity between key nodes involved in emotional and cognitive regulation, in particular reduced connectivity between the amygdala and default-mode network (DMN and between the dorsal attention network (DAN and a frontal node encompassing the superior and inferior frontal gyri (SFG/IFG and the anterior cingulate cortex (ACC, with further reductions as a function of dependency, lifetime exposure, and cycle state (on/off.

  10. Sudden or unnatural deaths involving anabolic-androgenic steroids.

    Science.gov (United States)

    Darke, Shane; Torok, Michelle; Duflou, Johan

    2014-07-01

    Anabolic-androgenic steroids (AASs) are frequently misused. To determine causes of death, characteristics, toxicology, and pathology of AAS positive cases, all cases (n = 24) presenting to the New South Wales Department of Forensic Medicine (1995-2012) were retrieved. All were male, and the mean age was 31.7 years. Deaths were mainly due to accidental drug toxicity (62.5%), then suicide (16.7%) and homicide (12.5%). Abnormal testosterone/epitestosterone ratios were reported in 62.5%, followed by metabolites of nandrolone (58.3%), stanozolol (33.3%), and methandienone (20.8%). In 23 of 24 cases, substances other than steroids were detected, most commonly psychostimulants (66.7%). In nearly half, testicular atrophy was noted, as was testicular fibrosis and arrested spermatogenesis. Left ventricular hypertrophy was noted in 30.4%, and moderate to severe narrowing of the coronary arteries in 26.1%. To summarize, the typical case was a male polydrug user aged in their thirties, with death due to drug toxicity. Extensive cardiovascular disease was particularly notable. © 2014 American Academy of Forensic Sciences.

  11. Steroid Androgen Exposure during Development Has No Effect on Reproductive Physiology of Biomphalaria glabrata.

    Directory of Open Access Journals (Sweden)

    Satwant Kaur

    Full Text Available Gastropod mollusks have been proposed as alternative models for male reproductive toxicity testing, due to similarities in their reproductive anatomy compared to mammals, together with evidence that endocrine disrupting chemicals can cause effects in some mollusks analogous to those seen in mammals. To test this hypothesis, we used the freshwater pulmonate snail, Biomphalaria glabrata, for which various genetic tools and a draft genome have recently become available, to investigate the effects of two steroid androgens on the development of mollusk secondary sexual organs. Here we present the results of exposures to two potent androgens, the vertebrate steroid; 5α-dihydrotestosterone (DHT and the pharmaceutical anabolic steroid; 17α-methyltestosterone (MT, under continuous flow-through conditions throughout embryonic development and up to sexual maturity. Secondary sexual gland morphology, histopathology and differential gene expression analysis were used to determine whether steroid androgens stimulated or inhibited organ development. No significant differences between tissues from control and exposed snails were identified, suggesting that these androgens elicited no biologically detectable response normally associated with exposure to androgens in vertebrate model systems. Identifying no effect of androgens in this mollusk is significant, not only in the context of the suitability of mollusks as alternative model organisms for testing vertebrate androgen receptor agonists but also, if applicable to other similar mollusks, in terms of the likely impacts of androgens and anti-androgenic pollutants present in the aquatic environment.

  12. Cardiotoxic effects of cocaine and anabolic-androgenic steroids in the athlete.

    Science.gov (United States)

    Welder, A A; Melchert, R B

    1993-04-01

    Cocaine and anabolic-androgenic steroid abuse have become major drug problems in the United States. Cocaine has been designated as "the drug of greatest national health concern" while as many as 1 million Americans have used or are currently using anabolic-androgenic steroids to promote athletic performance and/or improve physical appearance. Unfavorable cardiovascular events have been linked to both cocaine and anabolic-androgenic steroid abuse in healthy, physically active individuals. Deaths of several United States athletes in 1986 focused attention on the life-threatening cardiovascular consequences of cocaine abuse. Reports of myocardial injury with anabolic-androgenic steroid abuse are anecdotal. Nevertheless, case reports have illustrated the alarming cardiotoxic potential of these steroids in athletes. Anabolic-androgenic steroids were correlated to myocardial infarction in weight lifters and cardiomyopathy in a former professional football player. From the total emergency room episodes where cocaine was mentioned in 1990, approximately 66% of these episodes occurred in young individuals 18-29 years of age. Over 500,000 of the individuals currently taking anabolic-androgenic steroids for nonmedical purposes are high-school children. Because cocaine and anabolic-androgenic steroids are used improperly, more focus needs to be paid to the toxic mechanisms of their adverse effects. Therefore, the purpose of this review is to discuss mechanisms whereby exercise and/or exercise training may alter the cardiovascular responses to these drugs. Furthermore, we would like to illustrate that contrary to the popular belief, acute and chronic abuse of cocaine and anabolic-androgenic steroids have a negative impact on exercise performance.

  13. Effects of androgenic-anabolic steroids in athletes.

    Science.gov (United States)

    Hartgens, Fred; Kuipers, Harm

    2004-01-01

    Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone testosterone. They can exert strong effects on the human body that may be beneficial for athletic performance. A review of the literature revealed that most laboratory studies did not investigate the actual doses of AAS currently abused in the field. Therefore, those studies may not reflect the actual (adverse) effects of steroids. The available scientific literature describes that short-term administration of these drugs by athletes can increase strength and bodyweight. Strength gains of about 5-20% of the initial strength and increments of 2-5 kg bodyweight, that may be attributed to an increase of the lean body mass, have been observed. A reduction of fat mass does not seem to occur. Although AAS administration may affect erythropoiesis and blood haemoglobin concentrations, no effect on endurance performance was observed. Little data about the effects of AAS on metabolic responses during exercise training and recovery are available and, therefore, do not allow firm conclusions. The main untoward effects of short- and long-term AAS abuse that male athletes most often self-report are an increase in sexual drive, the occurrence of acne vulgaris, increased body hair and increment of aggressive behaviour. AAS administration will disturb the regular endogenous production of testosterone and gonadotrophins that may persist for months after drug withdrawal. Cardiovascular risk factors may undergo deleterious alterations, including elevation of blood pressure and depression of serum high-density lipoprotein (HDL)-, HDL2- and HDL3-cholesterol levels. In echocardiographic studies in male athletes, AAS did not seem to affect cardiac structure and function, although in animal studies these drugs have been observed to exert hazardous effects on heart structure and function. In studies of athletes, AAS were not found to damage the liver. Psyche and behaviour seem to be strongly affected by AAS

  14. Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids

    DEFF Research Database (Denmark)

    Rasmussen, Jon Jarløv; Schou, Morten; Selmer, Christian

    2017-01-01

    Objective: Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current...

  15. Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

    OpenAIRE

    Santos, Marcelo R. dos; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R. de; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

    2018-01-01

    OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, ...

  16. Anabolic Androgenic Steroid Use in Teens: Prevalence, Demographics, and Perception of Effects

    Science.gov (United States)

    Lorang, Melissa; Callahan, Bryan; Cummins, Kevin M.; Achar, Suraj; Brown, Sandra A.

    2011-01-01

    Multiple risks are associated with early use of anabolic androgenic steroids, yet public understanding is limited and teen use not uncommon. The present study surveyed 4,231 high school students to understand prevalence of use, association with athletics and other substance use and expectations of drug effects. While overall rates of steroid use…

  17. Biochemistry and physiology of anabolic androgenic steroids doping.

    Science.gov (United States)

    Lippi, G; Franchini, M; Banfi, G

    2011-05-01

    Anabolic Androgenic Steroids (AASs) are chemical and pharmacological derivatives of the male hormone testosterone which are widely used for increasing burst and sprinting activities in sports. Although AASs are thought to be transversal to the plurality of sports disciplines, they are principally misused by bodybuilders, weightlifters, shot, hammer, discus or javelin throwers, rugby and American football players as well as by swimmers and runners. AAS exert a kaleidoscope of effects on human biology, principally through the 5-α-reductase-mediated conversion into dihydrotestosterone, the aromatase-mediated conversion into female sex hormones, a competitive antagonism to the glucocorticoid receptors, the potential stimulation of erythropoietin secretion as well as psychoactive effects on the brain. The influence of AASs on physical performance is still undefined, since the large number of studies published so far have described discordant and often contradictory outcomes. Nevertheless, animal and human investigations support the hypothesis that the administration of AASs might increase lean body mass, muscle mass, and maximal voluntary strength especially in men, so that they would represent an appealing form of doping for increasing power capacity, sustaining intensive training periods and, last but not least, as a cosmetic muscle makeover. The aim of this article is to review the biochemistry, physiology and the ergogenic effects of AASs.

  18. Effects of anabolic androgenic steroids on chylomicron metabolism.

    Science.gov (United States)

    Morikawa, Aleksandra T; Maranhão, Raul C; Alves, Maria-Janieire N N; Negrão, Carlos E; da Silva, Jeferson L; Vinagre, Carmen G C

    2012-11-01

    To evaluate the effects of anabolic androgenic steroids (AAS) on chylomicron metabolism. An artificial lipid emulsion labeled with radioactive cholesteryl ester (CE) and triglycerides (TG) mimicking chylomicrons was intravenously injected into individuals who regularly weight trained and made regular use of AAS (WT+AAS group), normolipidemic sedentary individuals (SDT group) and individuals who also regularly weight trained but did not use AAS (WT group). Fractional clearance rates (FCR) were determined by compartmental analysis for emulsion plasma decay curves. FCR-CE for the WT+AAS group was reduced (0.0073 ± 0.0079 min(-1), 0.0155 ± 0.0100 min(-1), 0.0149 ± 0.0160 min(-1), respectively; p<0.05), FCR-TG was similar for both the WT and SDT groups. HDL-C plasma concentrations were lower in the WT+AAS group when compared to the WT and SDT groups (22 ± 13; 41 ± 7; 38 ± 13 mg/dL, respectively; p<0.001). Hepatic triglyceride lipase activity was greater in the WT+AAS group when compared to the WT and SDT groups (7243 ± 1822; 3898 ± 1232; 2058 ± 749, respectively; p<0.001). However, no difference was observed for lipoprotein lipase activity. Data strongly suggest that AAS may reduce the removal from the plasma of chylomicron remnants, which are known atherogenic factors. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Anabolic-androgenic steroid use among young Finnish males.

    Science.gov (United States)

    Mattila, V M; Rimpelä, A; Jormanainen, V; Sahi, T; Pihlajamäki, H

    2010-04-01

    The aim of the present study was to describe the lifetime occurrence and associated factors of anabolic-androgenic steroids (AAS) among young Finnish males. Of the 10 829 male conscripts (median age 19), 10 396 (96%) answered a questionnaire during the first days of their conscription in the years 2001-2007. The main outcome was lifetime AAS use. We also studied associations between 13 socioeconomic, health, and health behavioral background variables and AAS use by logistic regression. Eighty-nine (0.9%) respondents reported having used AAS. In addition, 26 (0.3%) respondents reported that they would use AAS if they could obtain them. In multivariate analysis, which included all significant variables and age, the strongest associated factors were weight training at fitness centers more than three times a week [odds ratio (OR) 11.8; 95% confidence interval (CI): 7.1-19.6], low educational status (OR 3.7; 95% CI: 2.0-7.0), and weekly drunkenness as drinking style (OR 2.4; 95% CI: 1.4-4.5). Sports other than weight training were not associated with AAS in our sample. The use of AAS is relatively uncommon among Finnish males. It is strongly associated with weight training at fitness centers but also with lower educational status and a drunkenness-oriented lifestyle. Prevention should be targeted at those males participating in weight training.

  20. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs

    Science.gov (United States)

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    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. PMID:26998755

  1. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs.

    Science.gov (United States)

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    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.

  2. A jaundiced bodybuilder Cholestatic hepatitis as side effect of injectable anabolic-androgenic steroids.

    Science.gov (United States)

    Boks, Marije N; Tiebosch, Anton T; van der Waaij, Laurens A

    2017-11-01

    The use of anabolic steroids is prevalent in recreational athletes. This case report describes a young amateur bodybuilder who was referred to our outpatient clinic with jaundice and loss of appetite due to cholestatic hepatitis. Additional tests including a liver biopsy made it likely that the hepatitis was caused by the injectable anabolic steroid trenbolone enanthate. Cholestatic hepatitis may not be limited to the use of oral anabolic-androgenic steroids, as is widely assumed. Therefore, and because of other side effects, the recreational use of all forms of anabolic steroids should be discouraged.

  3. Detection of anabolic androgenic steroid use by elite athletes and by members of the general public.

    Science.gov (United States)

    Anawalt, Bradley D

    2018-03-15

    Because national and international sports competitions are sources of community pride and financial revenue, there have been great efforts to prevent and detect the use of performance-enhancing drugs such as anabolic androgenic steroids by elite athletes. The World Anti-Doping Agency and its national affiliate anti-doping agencies have created sophisticated monitoring systems and advanced testing techniques to detect the use of banned substances including anabolic androgenic steroids by participants in international and national athletic competitions. The creation of a longitudinal monitoring program known as the biological passport is a recent, important development in the efforts to prevent and detect the use of banned performance-enhancing drugs and methods. The biological passport program consists of the measurement of urinary and blood markers of anabolic androgenic steroid use (and other banned drugs or methods) at baseline and at random times. A panel of experts reviews the longitudinal data and interprets the likelihood of the use of banned drugs and methods. These advances in anti-doping appear to be highly effective, but some athletes persist in their efforts to cheat the detection process. In addition, some members of the general public use anabolic androgenic steroids for a variety of reasons including to improve physical appearance or to enhance performance in athletics. Clinicians must depend on clinical acumen and the measurement of serum testosterone and gonadotropins to guide them in making a tentative diagnosis of anabolic androgenic steroid use. Definitive diagnosis requires that the patient disclose the use of the drugs. Because anabolic androgenic steroids are effective for improving certain aspects of physical performance, some elite athletes (and members of the general public) will continue to use these drugs. Effective efforts to curtail the use of these drugs will require decreasing the ease of access to them, continued advancements in

  4. 11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome.

    Science.gov (United States)

    O'Reilly, Michael W; Kempegowda, Punith; Jenkinson, Carl; Taylor, Angela E; Quanson, Jonathan L; Storbeck, Karl-Heinz; Arlt, Wiebke

    2017-03-01

    Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), but the exact origin of hyperandrogenemia remains a matter of debate. Recent studies have highlighted the importance of the 11-oxygenated C19 steroid pathway to androgen metabolism in humans. In this study, we analyzed the contribution of 11-oxygenated androgens to androgen excess in women with PCOS. One hundred fourteen women with PCOS and 49 healthy control subjects underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. Twenty-four-hour urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for homeostatic model assessment of insulin resistance. Baseline demographic data, including body mass index, were recorded. As expected, serum concentrations of the classic androgens testosterone (P PCOS. Mirroring this, serum 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone were significantly higher in PCOS than in control subjects, as was the urinary 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in patients with PCOS compared with control subjects [53.0% (interquartile range, 48.7 to 60.3) vs 44.0% (interquartile range, 32.9 to 54.9); P PCOS had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance. We show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.

  5. Increased blood pressure and aortic stiffness among abusers of anabolic androgenic steroids

    DEFF Research Database (Denmark)

    Rasmussen, Jon J; Schou, Morten; Madsen, Per L

    2018-01-01

    BACKGROUND: Abuse of anabolic androgenic steroids (AAS) is prevalent among recreational athletes and adverse effects on blood pressure (BP) and arterial stiffness could be substantial. Testosterone decreases natriuretic peptides which are key components in BP-regulation and may impair BP-homeosta......BACKGROUND: Abuse of anabolic androgenic steroids (AAS) is prevalent among recreational athletes and adverse effects on blood pressure (BP) and arterial stiffness could be substantial. Testosterone decreases natriuretic peptides which are key components in BP-regulation and may impair BP...

  6. Anabolic androgenic steroids reverse the beneficial effect of exercise on tendon biomechanics: an experimental study.

    Science.gov (United States)

    Tsitsilonis, Serafim; Chatzistergos, Panayiotis E; Panayiotis, Chatzistergos E; Mitousoudis, Athanasios S; Athanasios, Mitousoudis S; Kourkoulis, Stavros K; Stavros, Kourkoulis K; Vlachos, Ioannis S; Ioannis, Vlachos S; Agrogiannis, George; George, Agrogiannis; Fasseas, Konstantinos; Konstantinos, Fasseas; Perrea, Despina N; Despina, Perrea N; Zoubos, Aristides B; Aristides, Zoubos B

    2014-06-01

    The effect of anabolic androgenic steroids on tendons has not yet been fully elucidated. Aim of the present study was the evaluation of the impact of anabolic androgenic steroids on the biomechanical and histological characteristics of Achilles tendons. Twenty-four male Wistar rats were randomized into four groups with exercise and anabolic steroids (nandrolone decanoate) serving as variables. Protocol duration was 12 weeks. Following euthanasia, tendons' biomechanical properties were tested with the use of a modified clamping configuration. Histological examination with light and electron microscopy were also performed. In the group of anabolic steroids and exercise the lowest fracture stress values were observed, while in the exercise group the highest ones. Histological examination by light and electron microscopy revealed areas of collagen dysplasia and an increased epitendon in the groups receiving anabolic steroids and exercise. These findings suggest that anabolic androgenic steroids reverse the beneficial effect of exercise, thus resulting in inferior maximal stress values. Copyright © 2013 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  7. Detection of anabolic androgenic steroid abuse in doping control using mammalian reporter gene bioassays.

    Science.gov (United States)

    Houtman, Corine J; Sterk, Saskia S; van de Heijning, Monique P M; Brouwer, Abraham; Stephany, Rainer W; van der Burg, Bart; Sonneveld, Edwin

    2009-04-01

    Anabolic androgenic steroids (AAS) are a class of steroid hormones related to the male hormone testosterone. They are frequently detected as drugs in sport doping control. Being similar to or derived from natural male hormones, AAS share the activation of the androgen receptor (AR) as common mechanism of action. The mammalian androgen responsive reporter gene assay (AR CALUX bioassay), measuring compounds interacting with the AR can be used for the analysis of AAS without the necessity of knowing their chemical structure beforehand, whereas current chemical-analytical approaches may have difficulty in detecting compounds with unknown structures, such as designer steroids. This study demonstrated that AAS prohibited in sports and potential designer AAS can be detected with this AR reporter gene assay, but that also additional steroid activities of AAS could be found using additional mammalian bioassays for other types of steroid hormones. Mixtures of AAS were found to behave additively in the AR reporter gene assay showing that it is possible to use this method for complex mixtures as are found in doping control samples, including mixtures that are a result of multi drug use. To test if mammalian reporter gene assays could be used for the detection of AAS in urine samples, background steroidal activities were measured. AAS-spiked urine samples, mimicking doping positive samples, showed significantly higher androgenic activities than unspiked samples. GC-MS analysis of endogenous androgens and AR reporter gene assay analysis of urine samples showed how a combined chemical-analytical and bioassay approach can be used to identify samples containing AAS. The results indicate that the AR reporter gene assay, in addition to chemical-analytical methods, can be a valuable tool for the analysis of AAS for doping control purposes.

  8. Therapeutic effects of anabolic androgenic steroids on chronic diseases associated with muscle wasting

    NARCIS (Netherlands)

    Woerdeman, J.T.; de Ronde, W.

    2011-01-01

    Introduction: A variety of clinical conditions are complicated by loss of weight and skeletal muscle which may contribute to morbidity and mortality. Anabolic androgenic steroids have been demonstrated to increase fat-free mass, muscle mass and strength in healthy men and women without major adverse

  9. Determinants of Anabolic-Androgenic Steroid Risk Perceptions in Youth Populations: A Multivariate Analysis

    Science.gov (United States)

    Denham, Bryan E.

    2009-01-01

    Grounded conceptually in social cognitive theory, this research examines how personal, behavioral, and environmental factors are associated with risk perceptions of anabolic-androgenic steroids. Ordinal logistic regression and logit log-linear models applied to data gathered from high-school seniors (N = 2,160) in the 2005 Monitoring the Future…

  10. Anabolic Androgenic Steroids: Use and Perceived Use in Nonathlete College Students

    Science.gov (United States)

    Berning, Joseph M.; Adams, Kent J.; Debeliso, Mark; Stamford, Bryant A.; Newman, Ian M.

    2008-01-01

    Objective: The authors investigated the use and perceived use of anabolic androgenic steroids (AAS) among nonathlete college students. Participants: The authors surveyed a sample of 485 nonathlete college students at a major metropolitan university. Methods: They administered a survey on use and perceived use of AAS to the students. Results:…

  11. Anabolic-Androgenic Steroids: Knowledge about, Attitude toward, and Extent of Use by High School Students.

    Science.gov (United States)

    Yonker, R. J.; And Others

    Anabolic-androgenic steroids (AS) are pharmacologic derivatives of the hormone testosterone. They have therapeutic merit when used under a physician's prescription to treat certain hormonal imbalances and some forms of anemia; however, when taken in high doses they have a number of virilizing, feminizing, toxic, and psychological effects. This…

  12. Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction : a case study

    NARCIS (Netherlands)

    van Breda, E.; Keizer, H.A.; Kuipers, H.; Wolffenbuttel, B.H.R.

    The data of the present case demonstrate that the abuse of androgenic anabolic steroids (AAS) may lead to serious health effects. Although most clinical attention is usually directed towards peripheral side effects, the most serious central side effect, hypothalamic-pituitary-dysfunction, is often

  13. Anaboliske-androgene steroiders effekt på muskelstyrke, kropsvaegt og fedtfri legemsmasse hos styrketraenende maend

    DEFF Research Database (Denmark)

    Søe, Martin Jensen; Jensen, K L; Gluud, C

    1989-01-01

    A review of the effects of anabolic-androgenic steroids (AAS) on muscle strength, body weight and lean body mass in body-building men is presented. In about half of the placebo-controlled studies, a significant effect on the above mentioned response variables is found. In all cases where an effect...

  14. A simple chromatographic method for the radioimmunoassay of four androgenic steroids

    International Nuclear Information System (INIS)

    Bassett, R.M.

    1980-01-01

    Small Sephadex LH-20 columns were used to separate testosterone (T), 5α-dihydrotestosterone (DHT), Δ 4 -androstenedione (A) and dehydroepiandrosterone (DHA) present in serum prior to radioimmunoassay, to remove cross reacting steroids. The column successfully separated all major cross reactants and, where steroids overlapped, cross reactivity with the specific antiserum was low. The technique is simple, rapid, accurate, reproducible and inexpensive. Serum concentrations of these androgenic steroids in normal males and females were measured and were found to be comparable to previously published results. In hypogonadism, concentrations of testosterone in the male serum were significantly lower than in normal males. (UK)

  15. Adolescent anabolic/androgenic steroids: Aggression and anxiety during exposure predict behavioral responding during withdrawal in Syrian hamsters (Mesocricetus auratus).

    Science.gov (United States)

    Ricci, Lesley A; Morrison, Thomas R; Melloni, Richard H

    2013-11-01

    In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within-subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety-eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time. © 2013.

  16. Prevalence and awareness of anabolic androgenic steroid use ...

    African Journals Online (AJOL)

    Information on demographics, as well as the use of AAS, was included in ... the side effects of anabolic steroids among bodybuilders. Keywords: Anabolic ... These drugs are available by ..... and reproduction in any medium, provided the.

  17. Computational Assessment of Pharmacokinetics and Biological Effects of Some Anabolic and Androgen Steroids.

    Science.gov (United States)

    Roman, Marin; Roman, Diana Larisa; Ostafe, Vasile; Ciorsac, Alecu; Isvoran, Adriana

    2018-02-05

    The aim of this study is to use computational approaches to predict the ADME-Tox profiles, pharmacokinetics, molecular targets, biological activity spectra and side/toxic effects of 31 anabolic and androgen steroids in humans. The following computational tools are used: (i) FAFDrugs4, SwissADME and admetSARfor obtaining the ADME-Tox profiles and for predicting pharmacokinetics;(ii) SwissTargetPrediction and PASS online for predicting the molecular targets and biological activities; (iii) PASS online, Toxtree, admetSAR and Endocrine Disruptomefor envisaging the specific toxicities; (iv) SwissDock to assess the interactions of investigated steroids with cytochromes involved in drugs metabolism. Investigated steroids usually reveal a high gastrointestinal absorption and a good oral bioavailability, may inhibit someof the human cytochromes involved in the metabolism of xenobiotics (CYP2C9 being the most affected) and reflect a good capacity for skin penetration. There are predicted numerous side effects of investigated steroids in humans: genotoxic carcinogenicity, hepatotoxicity, cardiovascular, hematotoxic and genitourinary effects, dermal irritations, endocrine disruption and reproductive dysfunction. These results are important to be known as an occupational exposure to anabolic and androgenic steroids at workplaces may occur and because there also is a deliberate human exposure to steroids for their performance enhancement and anti-aging properties.

  18. Beyond T and DHT - novel steroid derivatives capable of wild type androgen receptor activation.

    Science.gov (United States)

    Mostaghel, Elahe A

    2014-01-01

    While androgen deprivation therapy (ADT) remains the primary treatment for metastatic prostate cancer (PCa), castration does not eliminate androgens from the prostate tumor microenvironment, and residual intratumoral androgens are implicated in nearly every mechanism by which androgen receptor (AR)-mediated signaling promotes castration-resistant disease. The uptake and intratumoral (intracrine) conversion of circulating adrenal androgens such as dehydroepiandrosterone sulfate (DHEA-S) to steroids capable of activating the wild type AR is a recognized driver of castration resistant prostate cancer (CRPC). However, less well-characterized adrenal steroids, including 11-deoxcorticosterone (DOC) and 11beta-hydroxyandrostenedione (11OH-AED) may also play a previously unrecognized role in promoting AR activation. In particular, recent data demonstrate that the 5α-reduced metabolites of DOC and 11OH-AED are activators of the wild type AR. Given the well-recognized presence of SRD5A activity in CRPC tissue, these observations suggest that in the low androgen environment of CRPC, alternative sources of 5α-reduced ligands may supplement AR activation normally mediated by the canonical 5α-reduced agonist, 5α-DHT. Herein we review the emerging data that suggests a role for these alternative steroids of adrenal origin in activating the AR, and discuss the enzymatic pathways and novel downstream metabolites mediating these effects. We conclude by discussing the potential implications of these findings for CRPC progression, particularly in context of new agents such as abiraterone and enzalutamide which target the AR-axis for prostate cancer therapy.

  19. Androgen - secreting steroid cell tumor of the ovary

    Directory of Open Access Journals (Sweden)

    Paras Ratilal Udhreja

    2014-01-01

    Full Text Available Steroid cell tumors (SCTs, not otherwise specified of the ovary are rare subgroup of sex cord tumors, which account for less than 0.1% of all ovarian tumors and also that will present at any age. The majority of these tumors produce steroids with testosterone being the most common. A case of a 28-year-old woman who presented with symptoms of virilization is reported. Although SCTs are generally benign, there is a risk for malignant transformation. Surgery is the most important and hallmark treatment.

  20. Comparison of steroid receptors from the androgen responsive DDT1 cell line and the nonresponsive HVP cell line.

    Science.gov (United States)

    Norris, J S; Kohler, P O

    1978-01-01

    Two hamster cell lines have been isolated from androgen target tissue. The DDT1 cells derived from ductus deferens tissue exhibit a growth response to androgens, while the HVP cells derived from ventral prostate are androgen unresponsive. Both cell lines contain androgen receptors, that are similar when compared by kinetic methods, sedimentation velocity, chromatographic procedures or nuclear translocation ability. The forms of the high salt extracted nuclear receptors are indistinguishable chromatographically. Therefore, we postulate that the lesion preventing androgen induced growth in the HVP cell line is subseqent to nuclear translocation of the steroid receptor complex.

  1. Endothelial function in male body builders taking anabolic androgenic steroids

    Directory of Open Access Journals (Sweden)

    H Hashemi

    2005-11-01

    Full Text Available Background: Adverse cardiovascular events have been reported in body builders taking anabolic steroids. Adverse effects of AAS on endothelial function can initiate atherosclerosis. This study evaluates endothelial function in body builders using AAS, compared with non-steroids using athletes as controls. Methods: We recruited 30 nonsmoking male body builders taking AAS, 14 in build up phase, 8 in work out phase, and 8 in post steroid phase, and 30 nonsmoking male athletes who denied ever using steroids. Serum lipids and fasting plasma glucose were measured to exclude dyslipidemia and diabetes. Brachial artery diameter was measured by ultrasound at rest, after cuff inflation, and after sublingual glyceriltrinitrate (GTN to determine flow mediated dilation (FMD, nitro mediated dilation (NMD and ratio of FMD to NMD (index of endothelial function. Result: Use of AAS was associated with higher body mass index (BMI and low density lipoprotein–cholesterol (LDL-C. Mean ratio of flow mediated dilatation after cuff deflation to post GTN dilatation of brachial artery (index of endothelial function in body builders taking AAS was significantly lower than control group (0.96(0.05 versus 1(0.08; p=0.03. After adjusting BMI, age and weight, no significant difference was seen in index of endothelial function between two groups (p=0 .21. Conclusion: Our study indicates that taking AAS in body builders doesn’t have direct effect on endothelial function. Future study with bigger sample size and measurement of AAS metabolites is recommended. Key words: endothelium, lipids, anabolic steroids, body builders

  2. The relationship between anabolic androgenic steroids and muscle dysmorphia: a review.

    Science.gov (United States)

    Rohman, Lebur

    2009-01-01

    This review explores the condition of muscle dysmorphia (MD) and its relationship with anabolic androgenic steroids (AAS). Particular emphasis is placed upon whether anabolic steroids are a predisposing, precipitating or perpetuating factor of MD. Furthermore, psychiatric complications of AAS abuse are examined. The current evidence from the literature suggests that AAS (ab)use is possibly a perpetuating factor in the evolution of MD. Psychiatric complications of AAS include mood and behavior changes, perceptual abnormalities, and withdrawal symptoms. In addition, there appears to be a credible dependence theory to AAS in fruition.

  3. The Buzz About Anabolic Androgenic Steroids: Electrophysiological Effects in Excitable Tissues

    Science.gov (United States)

    Oberlander, Joseph G.; Penatti, Carlos A. A.; Porter, Donna M.; Henderson, Leslie P.

    2012-01-01

    Anabolic androgenic steroids (AAS) comprise a large and growing class of synthetic androgens used clinically to promote tissue-building in individuals suffering from genetic disorders, injuries and diseases. Despite these beneficial therapeutic applications, the predominant use of AAS is illicit: these steroids are self-administered to promote athletic performance and body image. Hand in hand with the desired anabolic actions of the AAS are untoward effects on the brain and behavior. While the signaling routes by which the AAS impose both beneficial and harmful actions may be quite diverse, key endpoints are likely to include ligand-gated and voltage-dependent ion channels that govern the activity of electrically excitable tissues. Here we review the known effects of AAS on molecular targets that play critical roles in controlling electrical activity, with a specific focus on the effects of AAS on neurotransmission mediated by GABAA receptors in the central nervous system (CNS). PMID:22576754

  4. Therapeutic effects of anabolic androgenic steroids on chronic diseases associated with muscle wasting.

    Science.gov (United States)

    Woerdeman, Jorn; de Ronde, Willem

    2011-01-01

    A variety of clinical conditions are complicated by loss of weight and skeletal muscle which may contribute to morbidity and mortality. Anabolic androgenic steroids have been demonstrated to increase fat-free mass, muscle mass and strength in healthy men and women without major adverse events and therefore could be beneficial in these conditions. This review provides an overview of clinical trials with anabolic androgenic steroids in the treatment of chronic diseases including HIV-wasting, chronic renal failure, chronic obstructive lung disease, muscular disease, alcoholic liver disease, burn injuries and post operative recovery. Relevant studies were identified in PubMed (years 1950 - 2010), bibliographies of the identified studies and the Cochrane database. Although the beneficial effects of AAS in chronic disorders are promising, clinically relevant endpoints such as quality of life, improved physical functioning and survival were mainly missing or not significant, except for burn injuries. Therefore, more studies are needed to confirm their long term safety and efficacy.

  5. Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health.

    Science.gov (United States)

    Wu, Christopher; Kovac, Jason R

    2016-10-01

    There has recently been renewed interest in novel clinical applications of the anabolic-androgenic steroid (AAS) testosterone and its synthetic derivatives, particularly given with the rising popularity of testosterone supplementation therapy (TST) for the treatment of male hypogonadism. In this manuscript, we provide a brief review of the history of AAS and discuss clinical applications of two of the more well-known AAS: nandrolone and oxandrolone. Both agents exhibit favorable myotrophic/androgenic ratios and have been investigated for effectiveness in numerous disease states. We also provide a brief synopsis of selective androgen receptor modulators (SARMs) and postulate how these orally active, non-aromatizing, tissue-selective agents might be used in contemporary andrology. Currently, the applications of testosterone alternatives in hypogonadism are limited. However, it is tempting to speculate that these agents may one day become accepted as alternatives, or adjuncts, to the treatment of male hypogonadism.

  6. Gynecomastia in two young men with histories of prolonged use of anabolic androgenic steroids

    OpenAIRE

    Orlandi, M.A.; Venegoni, E.; Pagani, C.

    2010-01-01

    The aim of this report is to highlight the risk of anabolic androgenic steroid-induced gynecomastia in young men involved in nonagonistic sports and the role of ultrasonography in its diagnosis. The authors describe two cases of gynecomastia in nonprofessional weight lifters with histories of AAS use. In both cases, the diagnosis was based on patient history and clinical findings, but the sonographic examination confirmed the clinical suspicion and excluded the presence of other types of dise...

  7. Prolonged Hypogonadism in Males Following Withdrawal from Anabolic-Androgenic Steroids: an Underrecognized Problem

    Science.gov (United States)

    Kanayama, Gen; Hudson, James I.; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G.

    2015-01-01

    Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Outpatient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p treatment. Conclusions Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. PMID:25598171

  8. Anabolic-Androgenic Steroids - doi:10.5020/18061230.2007.p267

    Directory of Open Access Journals (Sweden)

    Urival Magno Gomes Ferreira

    2012-01-01

    Full Text Available There are evidences of the increase in the consumption of anabolic steroids and the damages to health caused by their indiscriminate use, mainly among children and youngsters. The anabolic-androgenic steroids (AAS consist in testosterone and its derivatives. They are produced endogenously in the testicles and adrenal cortex and are responsible for the secondary sexual characteristics associated to masculinity. Although the results of the exogenous use of AAS are still controversial, they have been used for the increase of physical strength and muscle mass. These substances are directly related to different clinical conditions such as: bladder cancer, coronary disease, gynecomastia, hepatic disorders and cancer, and sterility. This study aimed at approaching relevant topics related to the drugs action mechanisms, ways of use and metabolism, and side effects, besides the importance of the prevention in the use of those drugs in most diverse age groups. The abusive use of anabolic-androgenic steroids consists in a problem that has gradually occurred, which has given rise to laws, rules and support groups turned to the prevention, education and restriction of their use.

  9. Multidetection Of Anabolic Androgenic Steroids Using Immunoarrays and Pattern Recognition Techniques

    Science.gov (United States)

    Calvo, D.; Salvador, J. P.; Tort, N.; Centi, F.; Marco, M. P.; Marco, S.

    2009-05-01

    A first step towards the multidetection of anabolic androgenic steroids by Enzyme-linked immunosorbent assays (ELISA) has been performed in this study. This proposal combines an array of classical ELISA assays with different selectivities and multivariate data analysis techniques. Data has been analyzed by principal component analysis in conjunction with a k-nearest line classifier has been used. This proposal allows to detect simultaneously four different compounds in the range of concentration from 10-1.5 to 103 mM with a total rate of 90.6% of correct detection.

  10. Short QT interval is unreliable marker of anabolic androgenic steroid abuse in competitive athletes

    Directory of Open Access Journals (Sweden)

    Đorđević Vitomir

    2012-01-01

    Full Text Available Introduction. Previous animal and human studies provided the evidence that testosterone may affect ventricular repolarization by shortening of the QT interval. Synthetic derivatives of testosterone, modified to enhance its anabolic properties, are occasionally abused by some competitive athletes. Objective. We assessed whether the QT interval duration could discriminate androgenic anabolic steroids (AAS-using strength athletes (SA from drug-free endurance athletes (EA, by comparing 25 formulas for QT interval correction. Methods. We recruited 22 elite male athletes involved in long-term strength or endurance training and 20 sedentary controls. All elite

  11. A qualitative exploration of the motivations underlying anabolic-androgenic steroid use from adolescence into adulthood

    Directory of Open Access Journals (Sweden)

    Marc Ashley Harris

    2016-08-01

    Full Text Available Background This study explored the direct experience of anabolic androgenic steroid (AAS use by young men, with an emphasis on how motivations progressed from adolescent initiation to more entrenched usage. Participants and procedure Nine semi-structured interviews were conducted with individuals ranging in experience of AAS use, from novice to experienced users. Results The results indicated that the young adult men progressed through a clear transition whereby their motives for using these substances changed from a mere desire to compete with other men to more internalised body image problems. Conclusions The findings presented suggest a more complex relationship between AAS use and body image pathology than previously suggested.

  12. Hidden Danger of Irrational Abusing Illegal Androgenic-anabolic Steroids in Recreational Athletes Age Under 35 in Bosnia & Herzegovina.

    Science.gov (United States)

    Solakovic, Sid; Totic, Dragan; Vukas, Haris; Djedovic, Muhamed

    2015-06-01

    Androgenic-anabolic steroids are rarely used by sportsmen who want to improve physical performance in competition sport. Despite that they are well aware of the side effects of anabolic steroids, many young athletes in Bosnia and Herzegovina without competition motivation come in temptation, trying to achieve better muscle proportion and physical performance unknowing consequence of side effects and what is hiding behind. Risk factors such as increasing of lipid levels and arterial hypertension are major factors which have important role in the Pathogenesis of atherosclerosis and are responsible for occurrence of cardiovascular disease even causing a sudden death in young athletes. The aim of the study was to estimate the frequency of misusing of androgenic anabolic steroid drugs in young recreational sportsmen without competition motivation. This study will try to estimate vascular and lipid status, analyzing the side effects of steroids in young recreational athletes under the age of 35, in Bosnia and Herzegovina. The study included 70 individuals in period of 2010 till 2015 on recreational exercising program; 35 individuals misusing androgenic anabolic steroids during the period of 5 years were compared with 35 individuals which do not use androgenic anabolic steroids. Non-invasive methods were used in all individual (clinical examination and vascular ultrasound examination of vein system). The routine of training units in both groups was approximately two hours 4-6 times per week. Final analysis has reveal that in androgenic anabolic steroids group in 18 individuals or 55.7% arterial hypertension with hyperlipidemia was more represented, compared with the group without using anabolic steroids, represented by 2 individuals or 5.7% and it was statistically considered significant by using p value less than 0.05. (panabolic steroids drugs are males (100%) or 35 individuals; we did not find females using anabolic steroids and that is why our research was limited to

  13. Micronucleus as biomarkers of cancer risk in anabolic androgenic steroids users.

    Science.gov (United States)

    Souza, L da Cunha Menezes; da Cruz, L A; Cerqueira, E de Moraes Marcílio; Meireles, Jrc

    2017-03-01

    The use of anabolic androgenic steroids (AAS) has grown among practitioners of recreational bodybuilding, with significant contributions of designer steroids, aiming muscle hypertrophy in healthy subjects. The abusive use of AAS in general is associated with adverse effects; one of the most worrisome is cancer development. The aim of this study was to evaluate the effectiveness of the cytokinesis block micronucleus (CBMN) test in human lymphocytes in identifying risk groups for cancer development in users of AAS. Blood was collected from 15 AAS users bodybuilders (G1), 20 non-users bodybuilders (G2) and 20 non-users sedentary (G3). MN analysis was performed on a minimum of 1000 binucleated lymphocytes. The occurrence of MN was significantly higher ( p < 0.05) in individuals of G1 compared to G2 and G3. The results indicate the sensitivity of CBMN in human lymphocytes in the identification of chromosomal damage in consequence of AAS.

  14. Liver Toxicity of Anabolic Androgenic Steroid Use in an Adolescent with Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Awai, Hannah I; Yu, Elizabeth L; Ellis, Linda S; Schwimmer, Jeffrey B

    2013-01-01

    The prevalence of obesity and related morbidities such as nonalcoholic fatty liver disease (NAFLD) is high among adolescents. Current treatment recommendations for NAFLD focus on lifestyle optimization via nutrition and exercise. After encouraging exercise, many adolescents choose to participate in organized sports, which may lead to use of illicit substances such as anabolic androgenic steroids (AAS) to boost athletic performance. Approximately 3,000,000 individuals use non-therapeutic AAS at supra-physiologic doses in the United States.1 In 2012, 5.9% of adolescent boys reported steroid use in the previous year.2 We anticipate adolescents with pre-existing liver disease are at increased risk for AAS induced hepatotoxicity. We present such a case with IRB approval and written individual patient consent. PMID:23568051

  15. Mouldy feed: A possible explanation for the excretion of anabolic-androgenic steroids in horses.

    Science.gov (United States)

    Decloedt, A I; Bailly-Chouriberry, L; Vanden Bussche, J; Garcia, P; Popot, M-A; Bonnaire, Y; Vanhaecke, L

    2016-05-01

    To ensure fair competition and to protect the horse's welfare, horses have to compete on their own merits, without any unfair advantage that might follow the use of drugs. Therefore, regulatory authorities list all substances that are not allowed in competition, including most anabolic-androgenic steroids. As zero-tolerance is retained, the question arose whether the consumption of mouldy feed could lead to the excretion of steroids, due to the biotransformation of plant phytosterols to steroids. A rapid ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analytical method, previously validated according to AORC (Association of Official Racing Chemists) and EC (European Commission) guidelines, was used to measure steroids in different sample types. Multiple mouldy feed samples were tested for the presence of steroids. The effect of digestion was tested by in vitro simulation of the horse's hindgut in batch incubations. In most feed samples no steroids were detected, even when the products were mouldy. Mouldy corn however showed to contain up to 3.0 ± 0.4 µg/kg AED (4-androstenedione), the main testosterone precursor. This concentration increased when mouldy corn (with added phytosterols) was digested in vitro. An herbal phytosupplement also showed to contain α-testosterone. These results demonstrate that it is important to caution against the consumption of any feed or (herbal) supplement of which the detailed ingredients and quantitative analysis are unknown. The consumption of mouldy corn should especially be avoided, not only from a horse health and welfare point of view, but also to avoid possible inadvertent positive doping results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Anabolic-androgenic steroid use and involvement in violent behavior in a nationally representative sample of young adult males in the United States.

    Science.gov (United States)

    Beaver, Kevin M; Vaughn, Michael G; Delisi, Matt; Wright, John Paul

    2008-12-01

    We examined the effects of anabolic-androgenic steroid use on serious violent behavior. Multivariate models based on data from the National Longitudinal Study of Adolescent Health (N = 6823) were used to examine the association between lifetime and past-year self-reported anabolic-androgenic steroid use and involvement in violent acts. Compared with individuals who did not use steroids, young adult males who used anabolic-androgenic steroids reported greater involvement in violent behaviors after we controlled for the effects of key demographic variables, previous violent behavior, and polydrug use.

  17. Anabolic Androgenic Steroids and Intracellular Calcium Signaling: A Mini Review on Mechanisms and Physiological Implications

    Science.gov (United States)

    Vicencio, J.M.; Estrada, M.; Galvis, D.; Bravo, R.; Contreras, A.E.; Rotter, D.; Szabadkai, G.; Hill, J.A.; Rothermel, B.A.; Jaimovich, E.; Lavandero, S.

    2015-01-01

    Increasing evidence suggests that nongenomic effects of testosterone and anabolic androgenic steroids (AAS) operate concertedly with genomic effects. Classically, these responses have been viewed as separate and independent processes, primarily because nongenomic responses are faster and appear to be mediated by membrane androgen receptors, whereas long-term genomic effects are mediated through cytosolic androgen receptors regulating transcriptional activity. Numerous studies have demonstrated increases in intracellular Ca2+ in response to AAS. These Ca2+ mediated responses have been seen in a diversity of cell types, including osteoblasts, platelets, skeletal muscle cells, cardiac myocytes and neurons. The versatility of Ca2+ as a second messenger provides these responses with a vast number of pathophysiological implications. In cardiac cells, testosterone elicits voltage-dependent Ca2+ oscillations and IP3R-mediated Ca2+ release from internal stores, leading to activation of MAPK and mTOR signaling that promotes cardiac hypertrophy. In neurons, depending upon concentration, testosterone can provoke either physiological Ca2+ oscillations, essential for synaptic plasticity, or sustained, pathological Ca2+ transients that lead to neuronal apoptosis. We propose therefore, that Ca2+ acts as an important point of crosstalk between nongenomic and genomic AAS signaling, representing a central regulator that bridges these previously thought to be divergent responses. PMID:21443511

  18. Hidden Danger of Irrational Abusing Illegal Androgenic-anabolic Steroids in Recreational Athletes Age Under 35 in Bosnia & Herzegovina

    OpenAIRE

    Solakovic, Sid; Totic, Dragan; Vukas, Haris; Djedovic, Muhamed

    2015-01-01

    Introduction: Androgenic-anabolic steroids are rarely used by sportsmen who want to improve physical performance in competition sport. Despite that they are well aware of the side effects of anabolic steroids, many young athletes in Bosnia and Herzegovina without competition motivation come in temptation, trying to achieve better muscle proportion and physical performance unknowing consequence of side effects and what is hiding behind. Risk factors such as increasing of lipid levels and arter...

  19. The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats.

    Science.gov (United States)

    Vargas, Rafael Arêas; Oliveira, Leonardo Pires; Frankenfeld, Stephan; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Favorito, Luciano Alves; Sampaio, Francisco José Barcellos

    2013-01-01

    Many adverse effects have been associated with abuse of anabolic-androgenic steroids (AAS), including disorders of the urogenital tract. The objective of this study is to analyze the morphological modifications in the prostate ventral lobe of pubertal and adult rats chronically treated with AAS, using morphometric methods. We studied 39 male Wistar rats weighing between 400 g and 550 g. The rats were divided into four groups: (a) control rats, with 105 days of age (C105) (n = 7); (b) control rats with 65 days of age (C65) (n = 9), injected only with the vehicle (peanut oil); (c) treated rats, with 105 days of age (T105) (n = 10) and (d) treated rats with 65 days of age (T65) (n = 13). The treated rats were injected with nandrolone decanoate at a dose of 10 mg.Kg-1 body weight. The steroid hormone and the vehicle were administered by intramuscular injection once a week for eight weeks. The rats were killed at 161 days of age (C105 and T105) and 121 days of age (C65 and T65) and the ventral prostate lobe was dissected and processed for histology. The height of the acinar epithelium, the surface densities of the lumen, epithelium and stroma were observed with X400 magnification using an Olympus light microscope coupled to a Sony CCD video camera, and the images transferred to a Sony monitor KX14-CP1. The selected histological areas were then quantified using the M42 test-grid system on the digitized fields. The data were analyzed with the Graphpad software. To compare the quantitative data in both groups (controls and treated) and the outcomes, Student's t-test was used (p anabolic androgenic steroids in rats promotes structural changes in the prostate. We observed structural changes in the weight, volume and epithelium height of the prostate ventral lobe and a predominance of collagen fibers.

  20. Outline of a typology of men’s use of anabolic androgenic steroids in fitness and strength training environments

    DEFF Research Database (Denmark)

    Christiansen, Ask Vest; Vinther, Anders Schmidt; Liokaftos, Dimitrios

    2017-01-01

    Recent research into the use of anabolic androgenic steroids (AAS) in fitness and strength training environments have revealed great variance in users’ approach to AAS use and more specifically their approach to health risks and desired objectives. However, there have only been few attempts to de...

  1. Adolescent Self-Perceptions and Attitudes toward School as Determinants of Anabolic-Androgenic Steroid Risk Estimates and Normative Judgments

    Science.gov (United States)

    Denham, Bryan E.

    2011-01-01

    Grounded in symbolic interactionism and drawing on data gathered in the 2007 Monitoring the Future Study (n = 2,201), this research examines how self-esteem and perceived intelligence, as well as attitudes and behaviors related to school environments, associate with perceptions of anabolic-androgenic steroids. With perceived risk and…

  2. Long-Term Anabolic Androgenic Steroid Use Is Associated with Increased Atrial Electromechanical Delay in Male Bodybuilders

    Directory of Open Access Journals (Sweden)

    Mustafa Akçakoyun

    2014-01-01

    Full Text Available We investigated the effect of long-term supraphysiologic doses of anabolic androgenic steroids (AAS on atrial electromechanical delay (AEMD in male bodybuilders. We clearly demonstrated that long-term consumption of supraphysiologic doses of AAS is associated with higher values of inter- and intra-AEMD in healthy young bodybuilders.

  3. Exposure to media predicts use of dietary supplements and anabolic-androgenic steroids among Flemish adolescent boys.

    Science.gov (United States)

    Frison, Eline; Vandenbosch, Laura; Eggermont, Steven

    2013-10-01

    This study examined whether different types of media affect the use of dietary proteins and amino acid supplements, and intent to use anabolic-androgenic steroids. A random sample of 618 boys aged 11-18 years from eight schools in the Flemish part of Belgium completed standardized questionnaires as part of the Media and Adolescent Health Study. The survey measured exposure to sports media, appearance-focused media, fitness media, use of dietary supplements, and intent to use anabolic-androgenic steroids. Data were analyzed using logistic regressions and are presented as adjusted odds ratios (OR) and 95 % confidence intervals (CI); 8.6 % indicated to have used dietary proteins, 3.9 % indicated to have used amino acid supplements, and 11.8 % would consider using anabolic-androgenic steroids. After adjusting for fitness activity, exposure to fitness media was associated with the use of dietary proteins (OR = 7.24, CI = 2.25-23.28) and amino acid supplements (5.16, 1.21-21.92; 44.30, 8.25-238). Intent to use anabolic-androgenic steroids was associated with exposure to fitness media (2.38, 1.08-5.26; 8.07, 2.55-25.53) and appearance-focused media (6.02, 1.40-25.82; 8.94, 1.78-44.98). Sports media did not correlate with the use of dietary supplements and intent to use anabolic-androgenic steroids. Specific types of media are strong predictors of the use of supplements in adolescent boys. This provides an opportunity for intervention and prevention through the selection of fitness media as a communication channel. Health practitioners should also be aware that the contemporary body culture exerts pressure not only on girls but also on boys.

  4. Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping.

    Science.gov (United States)

    Solimini, R; Rotolo, M C; Mastrobattista, L; Mortali, C; Minutillo, A; Pichini, S; Pacifici, R; Palmi, I

    2017-03-01

    Anabolic Androgenic Steroids (AAS) abuse and misuse is nowadays a harmful habit involving both professional or recreational athletes, as well as general population. AAS are also frequently present in over-the-counter dietary supplements without being declared in the list of ingredients, leaving consumers unaware of the risks of adverse effects. Indeed, health risks of AAS consumption in pharmaceutical preparations or dietary complements seem still underestimated and under-reported. The variety of complications due to AAS misuse involves cardiovascular, central nervous, musculoskeletal and genitourinary systems of both males and females; psychiatric and behavioral effects, damages to metabolic system, skin and mainly liver. For instance, relevant concern has been raised by the AAS hepatotoxicity including adenoma, hepatocellular carcinoma, cholestasis, and peliosis hepatis. The present review reports the information available on the hepatotoxic effects of AAS use in professional and amateur athletes.

  5. The Use of Anabolic Androgenic Steroids and Polypharmacy: A Review of the Literature

    Science.gov (United States)

    Dodge, Tonya; Hoagland, Margaux F.

    2011-01-01

    Background A review of the literature was conducted to examine the relationship between the use of anabolic androgenic steroid (AAS) use and the use of other drugs. Methods Studies published between the years of 1995–2010 were included in the review. Results The use of AAS is positively associated with use of alcohol, illicit drugs and legal performance enhancing substances. In contrast, the relationship between AAS and the use of tobacco and cannabis are mixed. Conclusion Results of the review indicate that the relationship between AAS use and other substance use depends on the type of substance studied. Implications for treatment and prevention are discussed. Suggestions for future research are provided. PMID:21232881

  6. Abuse of anabolic-androgenic steroids and bodybuilding acne: an underestimated health problem.

    Science.gov (United States)

    Melnik, Bodo; Jansen, Thomas; Grabbe, Stephan

    2007-02-01

    Abuse of anabolic-androgenic steroids (AAS) by members of fitness centers and others in Germany has reached alarming dimensions. The health care system provides the illegal AAS to 48.1 % of abusers. Physicians are involved in illegal prescription of AAS and monitoring of 32.1 % of AAS abusers. Besides health-threatening cardiovascular, hepatotoxic and psychiatric long-term side effects of AAS, acne occurs in about 50 % of AAS abusers and is an important clinical indicator of AAS abuse, especially in young men 18-26 years of age. Both acne conglobata and acne fulminans can be induced by AAS abuse. The dermatologist should recognize bodybuilding acne, address the AAS abuse, and warn the patient about other potential hazards.

  7. Androgenic-anabolic steroids inhibited post-exercise hypotension: a case control study.

    Science.gov (United States)

    Junior, Jefferson F C R; Silva, Alexandre S; Cardoso, Glêbia A; Silvino, Valmir O; Martins, Maria C C; Santos, Marcos A P

    There is evidence of hypertensive effects caused by anabolic androgenic steroids (AAS). A single exercise session promotes the acute reduction of blood pressure, but the effects of AAS on this phenomenon are unknown. To investigate the post-exercise blood pressure response in androgenic-anabolic steroid users. Thirteen AAS users (23.9±4.3 years old) and sixteen controls (22.1±4.5 years old) performed a session of aerobic exercise. Heart rate and blood pressure were assessed before exercise and during a 60min post-exercise resting period. Repeated ANOVA measures were used to determine differences between the groups. While the control group had a significant reduction in post-exercise systolic blood pressure of up to 13.9±11.6mmHg at 40min, this phenomenon was limited among AAS users who reached a maximum of 6.2±11.5mmHg at 60min. The between groups comparison revealed significant higher post-exercise hypotension (PEH) for the control group at 30min (-12.9±14.1mmHg versus -2.9±7.6mmHg), 40min (-13.9±11.6mmHg versus -2.5±8.3mmHg), 50min (-13.9±13.9mmHg versus -5.0±7.9mmHg) and 60min (-12.5±12.8mmHg versus -6.2±11.5mmHg). There was no significant diastolic PEH in any of the groups. This study demonstrated impaired systolic post-exercise hypotension as a new adverse effect of AAS usage. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

  8. Development of anabolic-androgenic steroids purity certified reference materials for anti-doping.

    Science.gov (United States)

    Quan, Can; Su, Fuhai; Wang, Haifeng; Li, Hongmei

    2011-12-20

    The need for certified reference materials (CRM) of anabolic-androgenic steroids reference materials was emphasized by the Beijing 2008 Olympic game as a tool to improve comparability, ensuring accuracy and traceability of analytical results for competing athletes. The China National Institute of Metrology (NIM) responded to the state request by providing seven anabolic-androgenic steroids (AAS) reference materials for Beijing Olympic anti-doping, GBW (E) 100086-GBW (E) 100092. This work describes the production of the series of AAS CRMs, according to ISO Guides 34 and 35 [1,2], which comprises the material processing, homogeneity and stability assessment, CRMs' characterization including moisture content, trace metal content. The AASs' purity values were assigned with collaborative study involved eight laboratories applying high resolution liquid chromatography-diode array detector (HPLC-DAD). Homogeneity of the AAS CRMs were determined by an in-house validated liquid chromatographic methodology. Potential degradation during storage was also investigated and a shelf-life based on this value was established. The certified values of CRMs were 99.76±0.079%, 99.76±0.25%, 99.63±0.09%, 99.67±0.11%, 98.82±0.56%, 96.30±0.39% and 99.71±0.49% (purity±expanded uncertainty with confidence level of 95%) for methyltestosterone, testosterone propionate, nandrolone, nandrolone 17-propionate, boldenone, trenbolone acetate and testosterone respectively. The certified values for all the studied AAS reference materials are traceable to the international system of units (SI). The CRMs developed were applied by 32 laboratory including sports organizations and analytical laboratories during the 2008 Olympic game for anti-doping control. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes

    International Nuclear Information System (INIS)

    Allera, A.; Lo, S.; King, I.; Steglich, F.; Klingmueller, D.

    2004-01-01

    Various pesticides, industrial pollutants and synthetic compounds, to which human populations are exposed, are known or suspected to interfere with endogenous sex hormone functions. Such interference potentially affect the development and expression of the male and female reproductive system or both. Chemicals in this class are thus referred to as endocrine disruptors (ED). This emphazises on the relevance of screening ED for a wide range of sex hormone-mimicking effects. These compounds are believed to exert influence on hormonal actions predominantly by (i) interfering with endogenous steroids in that they functionally interact with plasma membrane-located receptors as well as with nuclear receptors both for estrogens and androgens or (ii) affecting the levels of sex hormones as a result of their impact on steroid metabolizing key enzymes. Essential sex hormone-related enzymes within the endocrine system of humans are aromatase, 5α-reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase I and phase II enzymes, respectively). Using suitable human tissues and human cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals suspected of acting as ED with androgenic or antiandrogenic activity (so-called AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In addition, the respective effects of six substances were also studied as positive controls due to their well-known specific hormonal agonistic/antagonistic activities. The aim of this report and subsequent investigations is to improve human health risk assessment for AAC and other ED

  10. The neurobiology and addiction potential of anabolic androgenic steroids and the effects of growth hormone.

    Science.gov (United States)

    Grönbladh, Alfhild; Nylander, Erik; Hallberg, Mathias

    2016-09-01

    Anabolic androgenic steroids (AAS) are substances that mimic the hormone testosterone, and primarily act via the androgen receptor. In addition to their physiological effect on muscle tissue and growth, research from the last decade has shown that AAS have a pronounced impact on the central nervous system. A large number of studies have demonstrated that AAS affect the mesolimbic reward system in the brain. However, whether the direct effects of AAS on endorphins, dopamine, serotonin and GABA etc. and on the corresponding and related systems lead to dependence needs to be further elucidated. According to recent studies, the prevalence of AAS dependence among AAS users has been estimated to be approximately 30%, and polysubstance use, of both pharmaceutical drugs and narcotics, within this group is common. The present review primarily discusses AAS in the context of addiction and dependence, and further addresses the issue of using multiple substances, i.e. stimulants and opiates in combination with AAS. In addition, aspects of the treatment of AAS dependence, the connection between AAS abuse and cognition, and AAS-induced neurotoxicity are presented. Currently, performance enhancing drugs are frequently used in combination with AAS. Therefore, a large section on growth hormone and insulin-like growth factor is also included. Copyright © 2016. Published by Elsevier Inc.

  11. The relationship between pubertal gynecomastia, prostate specific antigen, free androgen index, SHBG and sex steroids.

    Science.gov (United States)

    Kilic, Mustafa; Kanbur, Nuray; Derman, Orhan; Akgül, Sinem; Kutluk, Tezer

    2011-01-01

    To investigate the relationships between pubertal gynecomastia, prostate-specific antigen (PSA), free androgen index (FAI), sex hormone-binding globulin (SHBG) and sex steroids. A total of 61 male adolescents (10-17 years old; mean: 13.67 +/- 1.08) with gynecomastia were enrolled into the study group. A total of 65 healthy age-matched adolescents were included in the control group. Body mass index (BMI), Tanner staging, testis volume, stretched penis length (SPL) and bone age were evaluated. Serum follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), testosterone, free testosterone, SHBG, PSA levels were determined and FAI was calculated. In the study group, free testosterone (p = 0.012) and FAI (p = 0.05) were significantly lower than the control group. In the control group, SHBG levels decreased (p 0.05). High FAI was found to decrease the risk of gynecomastia (odds ratio: 0.211, 95% confidence interval: 0.064-0.694, p = 0.01). PSA showed a positive correlation with FAI, free testosterone, Tanner staging, testosterone, E2 and LH levels. PSA is a good indicator of androgen activity during puberty. However, owing to FAI remaining as the single significant variable for pubertal gynecomastia, we suggest that it is still the best parameter to elucidate the etiopathogenesis of gynecomastia as well as other pubertal developmental abnormalities in male adolescents, and further longitudinal studies are needed to investigate the relationships between PSA and FAI in puberty.

  12. Steroidal androgens and nonsteroidal, tissue-selective androgen receptor modulator, S-22, regulate androgen receptor function through distinct genomic and nongenomic signaling pathways.

    Science.gov (United States)

    Narayanan, Ramesh; Coss, Christopher C; Yepuru, Muralimohan; Kearbey, Jeffrey D; Miller, Duane D; Dalton, James T

    2008-11-01

    Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects.

  13. Androgenic anabolic steroid exposure during adolescence: Ramifications for brain development and behavior

    Science.gov (United States)

    Cunningham, Rebecca L.; Lumia, Augustus R.; McGinnis, Marilyn Y.

    2013-01-01

    Puberty is a critical period for brain maturation that is highly dependent on gonadal sex hormones. Modifications in the gonadal steroid environment, via the use of anabolic androgenic steroids (AAS), have been shown to affect brain development and behavior. Studies in both humans and animal models indicate that AAS exposure during adolescence alters normal brain remodeling, including structural changes and neurotransmitter function. The most commonly reported behavioral effect is an increase in aggression. Evidence has been presented to identify factors that influence the effect of AAS on the expression of aggression. The chemical composition of the AAS plays a major role in determining whether aggression is displayed, with testosterone being the most effective. The hormonal context, the environmental context, physical provocation and the perceived threat during the social encounter have all been found to influence the expression of aggression and sexual behavior. All of these factors point toward an altered behavioral state that includes an increased readiness to respond to a social encounter with heightened vigilance, and enhanced motivation. This AAS-induced state may be defined as emboldenment. The evidence suggests that the use of AAS during this critical period of development may increase the risk for maladaptive behaviors along with neurological disorders. PMID:23274699

  14. Interactions between opioids and anabolic androgenic steroids: implications for the development of addictive behavior.

    Science.gov (United States)

    Nyberg, Fred; Hallberg, Mathias

    2012-01-01

    Over the past decades, research on doping agents, such as anabolic androgenic steroids (AAS), has revealed that these compounds are often used in combination with other drugs of abuse. It seems that misuse of AAS probably involves more than a desire to enhance appearance or sports performance and studies have revealed that steroids are commonly connected with alcohol, opioids, tobacco, and psychotropic drugs. We have observed that AAS may interact with the endogenous opioids, excitatory amino acids, and dopaminergic pathways involved in the brain reward system. Furthermore, our studies provide evidence that AAS may induce an imbalance in these signal systems leading to an increased sensitivity toward opioid narcotics and central stimulants. In fact, studies performed in various clinics have shown that individuals taking AAS are likely to get addicted to opioids like heroin. This chapter reviews current knowledge on interactions between AAS and endogenous as well as exogenous opioids based not only on research in our laboratory but also on research carried out by several other clinical and preclinical investigators. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Chronic anabolic androgenic steroid usage associated with acute coronary syndrome in bodybuilder

    Directory of Open Access Journals (Sweden)

    Ertan Sonmez

    2016-03-01

    Full Text Available Introduction: It has been argued in current studies that anabolic androgenic steroids (AAS are misused by a great number of bodybuilders and athletes. However, there is diverse and often conflicting scientific data on the cardiac and metabolic complications caused by the misuse of AAS. There may be various reasons for myocardial infarction (MI with normal coronary arteries. However, for the majority of patients, the exact cause is still unknown. Case report: A 32 year-old male who was complaining about severe chest pain was admitted to our emergency department. He had been taking methenolone acetate 200 mg weekly for a period of three years for body building. His cardiac markers were significantly elevated and electrocardiogram (ECG showed peaked T waves in all derivations, which did not show ST elevation or depression. Both right and left coronary artery systems were found to be completely normal as a result of the angiogram. Conclusion: The purpose of this study is to show that AAS induced MI can be encountered with normal coronary arteries during acute coronary syndrome. Keywords: Bodybuilder, Anabolic steroids, Methenolone acetate, Acute coronary syndrome

  16. Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG).

    Science.gov (United States)

    Labrie, Fernand; Luu-The, Van; Martel, Céline; Chernomoretz, Ariel; Calvo, Ezequiel; Morissette, Jean; Labrie, Claude

    2006-07-01

    We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30,000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1mg) or DHEA (3mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p or =30%), in the prostate (ventral+dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds.

  17. Anabolic Androgenic Steroid (AAS) related deaths: autoptic, histopathological and toxicological findings.

    Science.gov (United States)

    Frati, Paola; Busardò, Francesco P; Cipolloni, Luigi; Dominicis, Enrico De; Fineschi, Vittorio

    2015-01-01

    Anabolic androgenic steroids (AASs) represent a large group of synthetic derivatives of testosterone, produced to maximize anabolic effects and minimize the androgenic ones. AAS can be administered orally, parenterally by intramuscular injection and transdermally. Androgens act by binding to the nuclear androgen receptor (AR) in the cytoplasm and then translocate into the nucleus. This binding results in sequential conformational changes of the receptor affecting the interaction between receptor and protein, and receptor and DNA. Skeletal muscle can be considered as the main target tissue for the anabolic effects of AAS, which are mediated by ARs which after exposure to AASs are up-regulated and their number increases with body building. Therefore, AASs determine an increase in muscle size as a consequence of a dose-dependent hypertrophy resulting in an increase of the cross-sectional areas of both type I and type II muscle fibers and myonuclear domains. Moreover, it has been reported that AASs can increase tolerance to exercise by making the muscles more capable to overload therefore shielding them from muscle fiber damage and improving the level of protein synthesis during recovery. Despite some therapeutic use of AASs, there is also wide abuse among athletes especially bodybuilders in order to improve their performances and to increase muscle growth and lean body mass, taking into account the significant anabolic effects of these drugs. The prolonged misuse and abuse of AASs can determine several adverse effects, some of which may be even fatal especially on the cardiovascular system because they may increase the risk of sudden cardiac death (SCD), myocardial infarction, altered serum lipoproteins, and cardiac hypertrophy. The aim of this review is to focus on deaths related to AAS abuse, trying to evaluate the autoptic, histopathological and toxicological findings in order to investigate the pathophysiological mechanism that underlines this type of death, which

  18. Physical appearance concerns are uniquely associated with the severity of steroid dependence and depression in anabolic-androgenic steroid users.

    Science.gov (United States)

    Griffiths, Scott; Jacka, Brendan; Degenhardt, Louisa; Murray, Stuart B; Larance, Briony

    2018-02-27

    Emerging research suggests that the sub-population of anabolic-androgenic steroid (AAS) users who experience physical appearance concerns may suffer greater psychological dysfunction than other sub-populations, including users with athletic or occupational concerns. Thus, among current AAS users, we sought to determine whether, and to what extent, social physique anxiety-an established measure of appearance concern-was associated with psychological dysfunction. Interviews were conducted with a sample of 74 male AAS users living in Australia. Users completed self-report instruments of the severity of AAS dependence, depression, hazardous and risky drinking, use of non-AAS illicit drugs, psychological side-effects due to AAS use and abnormal test results due to AAS use. Multivariate analyses revealed that greater social physique anxiety was uniquely associated with more severe symptoms of both AAS dependence and depression. Moreover, the effect size of these relationships was large. Social physique anxiety was not associated with hazardous or risky drinking, non-AAS illicit drug use, psychological side-effects or abnormal test results. Limitations notwithstanding, the study is consistent with the notion that AAS users who experience appearance concerns are at heightened risk of co-morbid psychological dysfunction. Given trends indicating an increase in the prevalence of AAS use in Australia and elsewhere, the findings suggest that health-care systems may need to consider prioritising the sub-population of AAS users who experience appearance concerns. Further investigation of the clinical syndrome of AAS dependence is required, including its relation to body image and eating disorders. © 2018 Australasian Professional Society on Alcohol and other Drugs.

  19. Treatment of Anabolic-Androgenic Steroid Dependence: Emerging Evidence and Its Implications

    Science.gov (United States)

    Kanayama, Gen; Brower, Kirk J.; Wood, Ruth I.; Hudson, James I.; Pope, Harrison G.

    2010-01-01

    Currently, few users of anabolic-androgenic steroids (AAS) seek substance-abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population—those who initiated AAS as youths in the 1980s—are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance-abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body-image disorders such as “muscle dysmorphia” may become dependent on AAS for their anabolic effects; these body-image disorders may respond to psychological therapies or pharmacologic treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals. PMID:20188494

  20. Treatment of anabolic-androgenic steroid dependence: Emerging evidence and its implications.

    Science.gov (United States)

    Kanayama, Gen; Brower, Kirk J; Wood, Ruth I; Hudson, James I; Pope, Harrison G

    2010-06-01

    Currently, few users of anabolic-androgenic steroids (AAS) seek substance abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population - those who initiated AAS as youths in the 1980s - are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body image disorders such as "muscle dysmorphia" may become dependent on AAS for their anabolic effects; these body image disorders may respond to psychological therapies or pharmacological treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  1. The risk environment of anabolic-androgenic steroid users in the UK: Examining motivations, practices and accounts of use.

    Science.gov (United States)

    Hanley Santos, Gisella; Coomber, Ross

    2017-02-01

    The numbers using illicit anabolic-androgenic steroids are a cause of concern for those seeking to reduce health harms. Using the 'risk environment' as a conceptual framework to better comprehend how steroid users' practices and perspectives impact on health risks, this paper examines steroid user motivations, patterns of use, and the ways in which these practices are accounted for. As part of a wider mixed-method study into performance and image enhancing drug (PIED) use and supply in one mid-sized city in South West England, qualitative interviews were undertaken with 22 steroid users. Participants were recruited from a local safer injecting service, rather than bodybuilding gyms, in order to access a wider cross-section of steroid users. A limitation of this approach is potential sample bias towards those showing more health optimising behaviours. The research findings highlight that patterns of steroid use varied according to motivation for use, experience and knowledge gained. Most reported having had little or no knowledge on steroids prior to use, with first use being based on information gained from fellow users or suppliers-sometimes inaccurate or incomplete. In accounting for their practices, many users differentiated themselves from other groups of steroid users-for example, older users expressed concern over patterns of use of younger and (what they saw as) inexperienced steroid users. Implicit in these accounts were intimations that the 'other' group engaged in riskier behaviour than they did. Examining social contexts of use and user beliefs and motivations is vital to understanding how 'risk' behaviours are experienced so that this, in turn, informs harm reduction strategies. This paper examines the ways in which use of steroids is socially situated and the implications of this for policy and practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Psychosocial correlates of gap time to anabolic-androgenic steroid use.

    Science.gov (United States)

    Klimek, Patrycja; Hildebrandt, Tom

    2018-03-15

    Theoretically, legal supplement use precedes and increases the risk for illicit appearance and performance enhancing drug (APED) use-also referred to as the gateway hypothesis. Little is known about associations between the speed of progression, or gap time, from legal to illicit APED use, and psychological risk factors, such as sociocultural influence, eating disorders, body image disturbance, and impulsivity. The sample taken from two studies included 172 active steroid users (n = 143) and intense-exercising healthy controls (n = 29) between the ages of 18 and 60 (M = 34.16, SD = 10.43), the majority of whom were male (91.9%). Participants, retrospectively, reported APED use and completed measures assessing psychological and behavioral factors, including eating concern, muscle dysmorphia, and impulsivity. Participants had a gap time from initial APED use to anabolic-androgenic steroid (AAS) use that ranged from 0 to 38 years. Continuous survival analysis indicated that interactions between self- versus other sociocultural influence on APED onset and both higher eating concern and impulsivity are associated with a shorter gap time from initial legal to illicit APED use. The results indicate the potential value in developing different strategies for individuals with other sociocultural versus self-influence on illicit APED use, and among more impulsive and eating-concerned APED users. Future research is needed to assess different trajectories of APED use, such that eating-concerned and impulsive individuals who perceive less other sociocultural influence may be at greatest risk for a speedier progression to AAS use. © 2018 Wiley Periodicals, Inc.

  3. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

    Directory of Open Access Journals (Sweden)

    J Abram McBride

    2016-01-01

    Full Text Available The use of testosterone replacement therapy (TRT for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.

  4. Anabolic-Androgenic Steroids and Condom Use: Potential Mechanisms in Adolescent Males

    Science.gov (United States)

    Blashill, Aaron J.; Gordon, Janna R.; Safren, Steven A.

    2013-01-01

    Previous research has revealed a significant bivariate relationship between anabolic androgenic steroid (AAS) use and reduced condom use among adolescent boys. However, to date, no known studies have explored the psychological mechanisms that may explain this relationship. Thus, the current study sought to examine two possible mediators in the association between AAS and condom use—depressive symptoms and substance use. Data were extracted from a nationally representative sample of U.S. adolescents. Participants were 3,780 U.S. high school boys who responded to self-report items assessing a number of health behaviors, including symptoms of depression, substance use, AAS use, and use of condoms during their most recent act of intercourse. Both depression and substance use were significant mediators in the relationship between AAS and condom use. However, when these effects were contrasted, the indirect effect of substance use was significantly stronger in magnitude than the effect of depression. Although AAS use is associated with sexual risk behaviors among adolescent boys, significant variance in this relationship is accounted for by elevated levels of depression and substance use, with substance use demonstrating a particularly salient pathway. PMID:23718635

  5. Anabolic-androgenic Steroid use and Psychopathology in Athletes. A Systematic Review

    Science.gov (United States)

    Piacentino, Daria; Kotzalidis, Georgios D.; del Casale, Antonio; Aromatario, Maria Rosaria; Pomara, Cristoforo; Girardi, Paolo; Sani, Gabriele

    2015-01-01

    The use of anabolic-androgenic steroids (AASs) by professional and recreational athletes is increasing worldwide. The underlying motivations are mainly performance enhancement and body image improvement. AAS abuse and dependence, which are specifically classified and coded by the DSM-5, are not uncommon. AAS-using athletes are frequently present with psychiatric symptoms and disorders, mainly somatoform and eating, but also mood, and schizophrenia-related disorders. Some psychiatric disorders are typical of athletes, like muscle dysmorphia. This raises the issue of whether AAS use causes these disorders in athletes, by determining neuroadaptive changes in the reward neural circuit or by exacerbating stress vulnerability, or rather these are athletes with premorbid abnormal personalities or a history of psychiatric disorders who are attracted to AAS use, prompted by the desire to improve their appearance and control their weights. This may predispose to eating disorders, but AASs also show mood destabilizing effects, with longterm use inducing depression and short-term hypomania; withdrawal/discontinuation may be accompanied by depression. The effects of AASs on anxiety behavior are unclear and studies are inconsistent. AASs are also linked to psychotic behavior. The psychological characteristics that could prompt athletes to use AASs have not been elucidated. PMID:26074746

  6. Multisubstance use as a feature of addiction to anabolic-androgenic steroids.

    Science.gov (United States)

    Skarberg, Kurt; Nyberg, Fred; Engstrom, Ingemar

    2009-01-01

    The aim of this study was to explore and describe total drug use among anabolic-androgenic steroid (AAS) users and the reasons given for the use of these drugs. The study was based on semi-structured interviews and questionnaires involving 32 patients who were attending an addiction centre in Orebro, Sweden, for AAS use. The results indicated that a history of polysubstance use among the patients was frequent. Over half were using drugs of abuse and also taking various other pharmaceuticals. Almost half of the patients took human growth hormones, and almost half of the interviewed persons were drinking alcohol to a hazardous or harmful extent. The most common reason given for taking AAS and other hormones was to increase muscle mass and strength, but some participants also used insulin as a means of losing fat. Cannabis was used to improve sleep, heroin to decrease pain and amphetamine to increase endurance and burn fat. Our data suggest that most of the current AAS users who have been admitted to a treatment programme are multiple drug users with polysubstance dependence. The study stresses the importance of carefully examining total drug use as part of the assessment regimen for this group. 2009 S. Karger AG, Basel.

  7. A high prevalence of abnormal personality traits in chronic users of anabolic-androgenic steroids.

    Science.gov (United States)

    Cooper, C J; Noakes, T D; Dunne, T; Lambert, M I; Rochford, K

    1996-01-01

    OBJECTIVE: (1) To assess the personality profiles of the anabolic androgenic steroid users (AAS) and (2) to determine whether valid premorbid personality traits could be obtained from cross sectional assessment using multisource data. METHODS: The first author became a participant-observer in a group of body builders. An experimental group of body builders who had been using AAS for no more than 18 months (n = 12) was identified. A group of control subjects, each of whom claimed that he did not, and never had, used AAS (n = 12) was also recruited during this period. Key informants played a crucial role in recruiting subjects representative of the AAS and body building communities. An interview schedule based on the Diagnostic and statistical manual of mental disorders (DSM3-R) personality disorder criteria was conducted with each subject. Additional data were obtained from an AAS using informant and significant others including family and friends. RESULTS: The user group was significantly heavier than the control group and showed abnormal personality traits, in contrast to the control group. Personality traits of AAS users before the onset of AAS use, assessed retrospectively, were not different from personality traits of control subjects. There were significant differences between the before and after personality traits in AAS user group. CONCLUSIONS: The results suggest (1) that AAS use is associated with significant disturbances in personality profile, and (2) that these personality disturbances are possibly the direct result of AAS use. PMID:8889121

  8. A high prevalence of abnormal personality traits in chronic users of anabolic-androgenic steroids.

    Science.gov (United States)

    Cooper, C J; Noakes, T D; Dunne, T; Lambert, M I; Rochford, K

    1996-09-01

    (1) To assess the personality profiles of the anabolic androgenic steroid users (AAS) and (2) to determine whether valid premorbid personality traits could be obtained from cross sectional assessment using multisource data. The first author became a participant-observer in a group of body builders. An experimental group of body builders who had been using AAS for no more than 18 months (n = 12) was identified. A group of control subjects, each of whom claimed that he did not, and never had, used AAS (n = 12) was also recruited during this period. Key informants played a crucial role in recruiting subjects representative of the AAS and body building communities. An interview schedule based on the Diagnostic and statistical manual of mental disorders (DSM3-R) personality disorder criteria was conducted with each subject. Additional data were obtained from an AAS using informant and significant others including family and friends. The user group was significantly heavier than the control group and showed abnormal personality traits, in contrast to the control group. Personality traits of AAS users before the onset of AAS use, assessed retrospectively, were not different from personality traits of control subjects. There were significant differences between the before and after personality traits in AAS user group. The results suggest (1) that AAS use is associated with significant disturbances in personality profile, and (2) that these personality disturbances are possibly the direct result of AAS use.

  9. Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids.

    Science.gov (United States)

    Rasmussen, Jon Jarløv; Schou, Morten; Selmer, Christian; Johansen, Marie Louise; Gustafsson, Finn; Frystyk, Jan; Dela, Flemming; Faber, Jens; Kistorp, Caroline

    2017-09-01

    Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current and former AAS abusers compared with controls. Cross-sectional study among men involved in recreational strength training. Current and former AAS abusers (n=37 and n=33) and controls (n=30) volunteered from the community. We assessed insulin sensitivity by Matsuda index (oral glucose tolerance test). Using overnight fasting blood samples, adiponectin and leptin were measured. Body composition and fat distribution, including visceral adipose tissue (VAT), were assessed by dual energy X-ray absorptiometry. Current and former AAS abusers displayed lower Matsuda index than controls (%-difference (95%CI) from controls, -26% (-45; -1) and -39% (-55; -18)). Testosterone was markedly higher among current AAS abusers and subnormal among former AAS abusers compared with controls. Current AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm 3 , P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In contrast, former AAS abusers showed highest leptin concentrations and body fat %. Multivariate linear regressions identified VAT as independent predictor of lower Matsuda index among current AAS abusers compared with controls; while body fat % independently predicted lower Matsuda index among former AAS abusers. Both current and former AAS abusers displayed lower insulin sensitivity which could be mediated by higher VAT and total body fat %, respectively. © 2017 John Wiley & Sons Ltd.

  10. Identifying a typology of men who use anabolic androgenic steroids (AAS).

    Science.gov (United States)

    Zahnow, Renee; McVeigh, Jim; Bates, Geoff; Hope, Vivian; Kean, Joseph; Campbell, John; Smith, Josie

    2018-05-01

    Despite recognition that the Anabolic Androgenic Steroid (AAS) using population is diverse, empirical studies to develop theories to conceptualise this variance in use have been limited. In this study, using cluster analysis and multinomial logistic regression, we identify typologies of people who use AAS and examine variations in motivations for AAS use across types in a sample of 611 men who use AAS. The cluster analysis identified four groups in the data with different risk profiles. These groups largely reflect the ideal types of people who use AAS proposed by Christiansen et al. (2016): Cluster 1 (You Only Live Once (YOLO) type, n = 68, 11.1%) were younger and motivated by fat loss; Cluster 2 (Well-being type, n = 236, 38.6%) were concerned with getting fit; Cluster 3 (Athlete type, n = 155, 25.4%) were motivated by muscle and strength gains; Cluster 4 (Expert type, n = 152, 24.9%) were focused on specific goals (i.e. not 'getting fit'). The results of this study demonstrate the need to make information about AAS accessible to the general population and to inform health service providers about variations in motivations and associated risk behaviours. Attention should also be given to ensuring existing harm minimisation services are equipped to disseminate information about safe intra-muscular injecting and ensuring needle disposal sites are accessible to the different types. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Adverse effects of doping with anabolic androgenic steroids (AAS) in competitive athletics, recreational sports and bodybuilding.

    Science.gov (United States)

    Vorona, Elena; Nieschlag, Eberhard

    2018-02-19

    Despite the fact that sports organizations and legislators have introduced various mechanisms to discourage athletes from using performance and appearance enhancing substances a high percentage of athletes admits to their unabated application. In competitive athletics, bodybuilding and in recreational sports anabolic androgenic steroids (AAS) continue to be the substances most abused. This review summarizes the side effects of AAS abuse on organs and system functions in both sexes. High doses of AAS cause a significant increase of erythrocytes und haemoglobin concentration, which may lead to thromboembolism, intracardiac thrombosis and stroke. Long-term AAS abusers have a higher incidence of arrhythmias, atherosclerosis, concentric left-ventricular myocardial hypertrophy with impaired diastolic function and also sudden cardiac death. Changes of liver function and structure, up to hepatocellular carcinoma, have been described, mainly in cases of chronic misuse of 17α-alkylated AAS. Sleeplessness, increased irritability, depressive mood status are often observed in AAS abuse. In former AAS abusers depression, anxiety and melancholy may persist for many years. Due to negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis AAS can cause reversible suppression of spermatogenesis up to azoospermia. In women the changes most often caused by AAS abuse are hirsutism, irreversible deepening of voice, dysmenorrhoea, secondary amenorrhoea with anovulation and infertility. AAS abuse notwithstanding, under clinical conditions testosterone remains the most important hormone for substitution therapy of male hypogonadism.

  12. Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

    Science.gov (United States)

    Kehinde, Elijah O; Akanji, Abayomi O; Al-Hunayan, Adel; Memon, Anjum; Luqmani, Yunus; Al-Awadi, Khaleel A; Varghese, Ramani; Bashir, Abdul Aziz; Daar, Abdallah S

    2006-04-01

    Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with

  13. Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle

    Science.gov (United States)

    Yu, Ji-Guo; Bonnerud, Patrik; Eriksson, Anders; Stål, Per S.; Tegner, Yelverton; Malm, Christer

    2014-01-01

    The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained

  14. Structural Brain Imaging of Long-Term Anabolic-Androgenic Steroid Users and Nonusing Weightlifters.

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    Bjørnebekk, Astrid; Walhovd, Kristine B; Jørstad, Marie L; Due-Tønnessen, Paulina; Hullstein, Ingunn R; Fjell, Anders M

    2017-08-15

    Prolonged high-dose anabolic-androgenic steroid (AAS) use has been associated with psychiatric symptoms and cognitive deficits, yet we have almost no knowledge of the long-term consequences of AAS use on the brain. The purpose of this study is to investigate the association between long-term AAS exposure and brain morphometry, including subcortical neuroanatomical volumes and regional cortical thickness. Male AAS users and weightlifters with no experience with AASs or any other equivalent doping substances underwent structural magnetic resonance imaging scans of the brain. The current paper is based upon high-resolution structural T1-weighted images from 82 current or past AAS users exceeding 1 year of cumulative AAS use and 68 non-AAS-using weightlifters. Images were processed with the FreeSurfer software to compare neuroanatomical volumes and cerebral cortical thickness between the groups. Compared to non-AAS-using weightlifters, the AAS group had thinner cortex in widespread regions and significantly smaller neuroanatomical volumes, including total gray matter, cerebral cortex, and putamen. Both volumetric and thickness effects remained relatively stable across different AAS subsamples comprising various degrees of exposure to AASs and also when excluding participants with previous and current non-AAS drug abuse. The effects could not be explained by differences in verbal IQ, intracranial volume, anxiety/depression, or attention or behavioral problems. This large-scale systematic investigation of AAS use on brain structure shows negative correlations between AAS use and brain volume and cortical thickness. Although the findings are correlational, they may serve to raise concern about the long-term consequences of AAS use on structural features of the brain. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Ruptured Tendons in Anabolic-Androgenic Steroid Users: A Cross-Sectional Cohort Study.

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    Kanayama, Gen; DeLuca, James; Meehan, William P; Hudson, James I; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Micheli, Lyle; Pope, Harrison G

    2015-11-01

    Accumulating case reports have described tendon rupture in men who use anabolic-androgenic steroids (AAS). However, no controlled study has assessed the history of tendon rupture in a large cohort of AAS users and comparison nonusers. Men reporting long-term AAS abuse would report an elevated lifetime incidence of tendon rupture compared with non-AAS-using bodybuilders. Cohort study; Level of evidence, 3. Medical histories were obtained from 142 experienced male bodybuilders aged 35 to 55 years recruited in the course of 2 studies. Of these men, 88 reported at least 2 years of cumulative lifetime AAS use, and 54 reported no history of AAS use. In men reporting a history of tendon rupture, the circumstances of the injury, prodromal symptoms, concomitant drug or alcohol use, and details of current and lifetime AAS use (if applicable) were recorded. Surgical records were obtained for most participants. Nineteen (22%) of the AAS users, but only 3 (6%) of the nonusers, reported at least 1 lifetime tendon rupture. The hazard ratio for a first ruptured tendon in AAS users versus nonusers was 9.0 (95% CI, 2.5-32.3; P weightlifting, with the majority occurring during other sports activities. Eight (26%) ruptures followed prodromal symptoms of nonspecific pain in the region. Virtually all ruptures were treated surgically, with complete or near-complete ultimate restoration of function. AAS abusers, compared with otherwise similar bodybuilders, showed a markedly increased risk of tendon ruptures, particularly upper-body tendon rupture. © 2015 The Author(s).

  16. EXTENDED THEORY OF PLANNED BEHAVIOR AS MODEL OF ANABOLIC ANDROGENIC STEROID USE BY INDONESIAN BODYBUILDERS

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    Shine Pintor Siolemba Patiro

    2016-01-01

    Full Text Available This correlational study explored the psychological antecedents of Indonesian bodybuilders’ intentions to use anabolic–androgenic steroids (AAS, based on the Theory of Planned Behavior (TPB. The purpose of this research was to identify factors that influence an Indonesian bodybuilder’s intention to use AAS and offer a better understanding of AAS use behavior based on the extended Theory of Planned Behavior (TPB. The three predictor variables of (1 attitude, (2 subjective norms, and (3 perceived behavioral control accounted for the variation in the outcome measure of the intention to reuse the AAS. Likewise, (1 attitude and (2 intention accounted for of the variation in the outcome measure of the reuse of AAS. This research combined two methods which are qualitative and quantitative. The respondents who were used in this research are professional bodybuilders located in Jakarta, Bandung, Surabaya, and Yogyakarta. The result of this research shows that the attitude of bodybuilders in using AAS tends to have values that are adopted by themselves. The result of this research differs from Bagozzi et al (1989 who stated that attitude influenced behavior directly as a nonpurposeful reaction or indirectly through intention as an aimed response. The result of this research clearly shows that attitude can influence behavior directly as a purposeful reaction, because the bodybuilders consume AAS to achieve a particular purpose and it is strengthened by achievement value in themselves. This research suggests also that attitude and subjective norms are not causally independent. They appear to reflect similar beliefs and to influence each other. These results differ from Titah and Barki (2009, as suggested by Chang (1998 and Aarts et al. (1998, who stated that a person whose positive subjective norms move them toward overt behavior, it will lead to a positive attitude toward the behavior. Future research directions are suggested regarding several areas

  17. The development of multiple drug use among anabolic-androgenic steroid users: six subjective case reports

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    Nyberg Fred

    2008-11-01

    Full Text Available Abstract Background The inappropriate use of anabolic androgenic steroids (AAS was originally a problem among athletes but AAS are now often used in nonsport situations and by patients attending regular addiction clinics. The aim of this study was to improve understanding of the development of multiple drug use in patients seeking treatment at an addiction clinic for AAS-related problems. Methods We interviewed six patients (four men and two women with experience of AAS use who were attending an addiction clinic for what they believed were AAS-related problems. The patients were interviewed in-depth about their life stories, with special emphasis on social background, substance use, the development of total drug use and subjective experienced psychological and physical side effects. Results There was significant variation in the development of drug use in relation to social background, onset of drug use, relationship to AAS use and experience of AAS effects. All patients had initially experienced positive effects from AAS but, over time, the negative experiences had outweighed the positive effects. All patients were dedicated to excess training and took AAS in combination with gym training, indicating that the use of these drugs is closely related to this form of training. Use of multiple drugs was common either in parallel with AAS use or serially. Conclusion The study shows the importance of understanding how AAS use can develop either with or without the concomitant use of other drugs of abuse. The use of AAS can, however, progress to the use of other drugs. The study also indicates the importance of obtaining accurate, comprehensive information about the development of AAS use in designing treatment programmes and prevention strategies in this area.

  18. Recreational Anabolic-Androgenic Steroid Use Associated With Liver Injuries Among Brazilian Young Men.

    Science.gov (United States)

    Schwingel, Paulo Adriano; Cotrim, Helma Pinchemel; Santos, Crimério Ribeiro dos; Santos, Adriano Oliveira dos; Andrade, Antônio Ricardo Cardia Ferraz de; Carruego, Marcos Vinicius Vilas Boas; Zoppi, Cláudio Cesar

    2015-01-01

    The recreational use of anabolic-androgenic steroids (AAS) has reached alarming levels among healthy people. However, several complications have been related to consumption of these drugs, including liver disorders. To evaluate the prevalence of liver injuries in young Brazilian recreational AAS users. Between February/2007 and May/2012 asymptomatic bodybuilders who were ≥18 years old and reported AAS use for ≥6 months were enrolled. All had clinical evaluations, abdominal ultrasound (AUS), and blood tests. 182 individuals were included in the study. The median age (interquartile range) was 26.0 years (22.0-30.0) and all were male. Elevated liver enzyme levels were observed in 38.5% (n = 70) of AAS users, and creatine phosphokinase was normal in 27.1% (n = 19) of them. Hepatic steatosis was observed by AUS in 12.1% of the sample. One individual had focal nodular hyperplasia and another had hepatocellular adenoma. One case each of hepatitis B and C virus infection was found. A diagnosis of toxic liver injury was suggested in 23 (12.6%) AAS users without a history of alcohol or other medications/drugs consumption, or evidence of other liver diseases. Young Brazilian recreational AAS users presented a wide spectrum of liver injuries that included hepatotoxicity, fatty liver, and liver neoplasm. They also presented risk factors for liver diseases such as alcohol consumption and hepatitis B and C virus infection. The results suggest that the risk of AAS use for the liver may be greater than the esthetic benefits, and demonstrate the importance of screening AAS users for liver injuries.

  19. Anabolic/androgenic steroid administration during adolescence and adulthood differentially modulates aggression and anxiety.

    Science.gov (United States)

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2015-03-01

    Anabolic/androgenic steroid (AAS) use remains high in both teens and adults in the U.S. and worldwide despite studies showing that AAS use is associated with a higher incidence of aggression and anxiety. Recently we showed that chronic exposure to AAS through adolescence increases aggression and decreases anxious behaviors, while during AAS-withdrawal aggression is lowered to species-normative levels and anxiety increases. AAS exposure is known to differentially alter behaviors and their underlying neural substrates between adults and adolescents and thus the current study investigated whether exposure to AAS during adulthood affects the relationship between aggression and anxiety in a manner similar to that previously observed in adolescents. Male hamsters were administered a moderate dose of AAS (5.0mg/kg/day×30days) during adolescence (P27-56) or young adulthood (P65-P94) and then tested for aggression and anxiety during AAS exposure (i.e., on P57 or P95) and during AAS withdrawal (i.e., 30days later on P77 or P115). Adolescent exposure to AAS increased aggressive responding during the AAS exposure period and anxiety-like responding during AAS withdrawal. Neither behavior was similarly influenced by adult exposure to AAS. Adult AAS exposure produced no difference in aggressive responding during AAS exposure (P95) or AAS withdrawal (P115); however, while AAS exposure during adulthood produced no difference in anxiety-like responding during AAS exposure, adult hamsters administered AAS were less anxious than vehicle control animals following AAS withdrawal. Together these data suggest that the aggression and anxiety provoking influence of AAS are likely a developmental phenomenon and that adult exposure to AAS may be anxiolytic over the long term. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway: Insights into enzyme activities and steroid fluxes in healthy infants during the first year of life from the urinary steroid metabolome.

    Science.gov (United States)

    Dhayat, Nasser A; Dick, Bernhard; Frey, Brigitte M; d'Uscio, Claudia H; Vogt, Bruno; Flück, Christa E

    2017-01-01

    The steroid profile changes dramatically from prenatal to postnatal life. Recently, a novel backdoor pathway for androgen biosynthesis has been discovered. However, its role remains elusive. Therefore, we investigated androgen production from birth to one year of life with a focus on minipuberty and on production of androgens through the backdoor pathway. Additionally, we assessed the development of the specific steroid enzyme activities in early life. To do so, we collected urine specimens from diapers in 43 healthy newborns (22 females) at 13 time points from birth to one year of age in an ambulatory setting, and performed in house GC-MS steroid profiling for 67 steroid metabolites. Data were analyzed for androgen production through the classic and backdoor pathway and calculations of diagnostic ratios for steroid enzyme activities were performed. Analysis revealed that during minipuberty androgen production is much higher in boys than in girls (e.g. androsterone (An)), originates largely from the testis (An boys -An girls ), and uses predominantly the alternative backdoor pathway (An/Et; Δ5metabolome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Supraphysiological Doses of Performance Enhancing Anabolic-Androgenic Steroids Exert Direct Toxic Effects on Neuron-like Cells

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    John Robert Basile

    2013-05-01

    Full Text Available Anabolic-androgenic steroids (AAS are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  2. Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.

    Science.gov (United States)

    Rosen, J; Negro-Vilar, A

    2002-03-01

    A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly

  3. Current status and bioanalytical challenges in the detection of unknown anabolic androgenic steroids in doping control analysis.

    Science.gov (United States)

    Pozo, Oscar J; De Brabanter, Nik; Fabregat, Andreu; Segura, Jordi; Ventura, Rosa; Van Eenoo, Peter; Deventer, Koen

    2013-11-01

    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.

  4. Self-Reported Use of Anabolic-Androgenic Steroids by Elite Power Lifters.

    Science.gov (United States)

    Yesalis III, Charles E.; And Others

    1988-01-01

    Thirty-three percent of a sample of 45 power lifters surveyed by questionnaire admitted to using steroids, while 55 percent of 20 lifters surveyed by phone admitted steroid use. The researchers suggest that there was significant underreporting by these athletes, who consider steroids primarily as a means to improve athletic performance. (IAH)

  5. Statistical analysis of fragmentation patterns of electron ionization mass spectra of enolized-trimethylsilylated anabolic androgenic steroids

    Science.gov (United States)

    Fragkaki, A. G.; Angelis, Y. S.; Tsantili-Kakoulidou, A.; Koupparis, M.; Georgakopoulos, C.

    2009-08-01

    Anabolic androgenic steroids (AAS) are included in the List of prohibited substances of the World Anti-Doping Agency (WADA) as substances abused to enhance athletic performance. Gas chromatography coupled to mass spectrometry (GC-MS) plays an important role in doping control analyses identifying AAS as their enolized-trimethylsilyl (TMS)-derivatives using the electron ionization (EI) mode. This paper explores the suitability of complementary GC-MS mass spectra and statistical analysis (principal component analysis, PCA and partial least squares-discriminant analysis, PLS-DA) to differentiate AAS as a function of their structural and conformational features expressed by their fragment ions. The results obtained showed that the application of PCA yielded a classification among the AAS molecules which became more apparent after applying PLS-DA to the dataset. The application of PLS-DA yielded a clear separation among the AAS molecules which were, thus, classified as: 1-ene-3-keto, 3-hydroxyl with saturated A-ring, 1-ene-3-hydroxyl, 4-ene-3-keto, 1,4-diene-3-keto and 3-keto with saturated A-ring anabolic steroids. The study of this paper also presents structurally diagnostic fragment ions and dissociation routes providing evidence for the presence of unknown AAS or chemically modified molecules known as designer steroids.

  6. Cardiomyopathy and Cerebrovascular Accident Associated with Anabolic-Androgenic Steroid Use.

    Science.gov (United States)

    Mochizuki, Ronald M.; Richter, Kenneth J.

    1988-01-01

    A case report is presented of a 32 year-old male bodybuilder who sustained an ischemic cerebrovascular accident and showed signs of cardiomyopathy. Although no cause was found, the man had been taking steroids for 16 years. Harmful effects of steroid use are discussed. (IAH)

  7. CDNA CLONING OF FATHEAD MINNOW (PIMEPHALES PROMELAS) ESTROGEN AND ANDROGEN RECEPTORS FOR USE IN STEROID RECEPTOR EXTRAPOLATION STUDIES FOR ENDOCRINE DISRUPTING CHEMICALS

    Science.gov (United States)

    cDNA Cloning of Fathead minnow (Pimephales promelas) Estrogen and Androgen Receptors for Use in Steroid Receptor Extrapolation Studies for Endocrine Disrupting Chemicals. Wilson, V.S.1,, Korte, J.2, Hartig P. 1, Ankley, G.T.2, Gray, L.E., Jr 1, , and Welch, J.E.1. 1U.S...

  8. Side effects of anabolic androgenic steroids: pathological findings and structure-activity relationships.

    Science.gov (United States)

    Büttner, Andreas; Thieme, Detlef

    2010-01-01

    Side effects of anabolic steroids with relevance in forensic medicine are mainly due to life-threatening health risks with potential fatal outcome and cases of uncertain limitations of criminal liability after steroid administration. Both problems are typically associated with long-term abuse and excessive overdose of anabolic steroids. Side effects may be due to direct genomic or nongenomic activities (myotrophic, hepatotoxic), can result from down-regulation of endogenous biosynthesis (antiandrogenic) or be indirect consequence of steroid biotransformation (estrogenic).Logically, there are no systematic clinical studies available and the number of causally determined fatalities is fairly limited. The following compilation reviews typical abundant observations in cases where nonnatural deaths (mostly liver failure and sudden cardiac death) were concurrent with steroid abuse. Moreover, frequent associations between structural characteristics and typical side effects are summarized.

  9. Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

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    Freddyson J Martínez-Rivera

    Full Text Available The abuse of anabolic androgenic steroids (AAS has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH. In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17α-methyltestosterone (17α-meT; 1 μM. These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

  10. Development of Hepatocellular Carcinoma Associated with Anabolic Androgenic Steroid Abuse in a Young Bodybuilder: A Case Report

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    Aline Hardt

    2012-01-01

    Full Text Available Introduction. Many different etiological factors are involved in the development of hepatocellular carcinoma (HCC. We report the case of HCC in a 37-year-old male professional bodybuilder with extensive anabolic androgenic (AAS steroid abuse. Case Presentation. Because of increasing epigastric and abdominal pain, abdominal ultrasound was performed in a 37-year-old male professional bodybuilder. A hyperechoic lesion in the liver was detected in segment VI. The magnetic resonance imaging showed hepatomegaly and confirmed the lesion, which showed features of a hepatocellular adenoma (HCA. Laboratory values were inconspicuous. After laparoscopic segmentectomy the histological examination revealed HCC. Conclusion. While the development of HCA in the liver by chronic intake of AAS is well known, little is known about the association with HCC. The presented case may indicate aetiological association of chronic intake of AAS and the development of HCC.

  11. Acute myocardial infarction in a young bodybuilder taking anabolic androgenic steroids: A case report and critical review of the literature.

    Science.gov (United States)

    Christou, Georgios A; Christou, Konstantinos A; Nikas, Dimitrios N; Goudevenos, John A

    2016-11-01

    We describe a case report of a 30-year-old bodybuilder suffering acute myocardial infarction (AMI). He had been taking stanozolol and testosterone for two months. The coronary angiogram showed high thrombotic burden in the left anterior descending artery without underlying atherosclerosis. Few case reports of AMI in athletes taking anabolic androgenic steroids (AASs) have been reported so far. AAS-related AMI is possibly underreported in the medical literature due to the desire of the affected individuals to hide AAS use. Physicians should always consider the possibility of AAS abuse in the context of a young athlete suffering AMI. AASs can predispose to AMI through the acceleration of coronary atherosclerosis. Additionally, thrombosis without underlying atherosclerosis or vasospasm is highly possible to cause AMI in AAS users. Complications after AMI may be more frequent in AAS users. © The European Society of Cardiology 2016.

  12. Androgen Secreting Steroid Cell Tumor of the Ovary Represented with Postmenopasal Bleeding and Extensive Hirsutism

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    Jadranka Georgievska

    2013-12-01

    Conclusion: In adult patients with hirsutism and elevated serum testosterone a possibility of a presence of an ovarian steroid cell tumor should be considered. Surgery is the main treatment of such patients.

  13. Anabolic androgenic steroids and violent offending: confounding by polysubstance abuse among 10,365 general population men.

    Science.gov (United States)

    Lundholm, Lena; Frisell, Thomas; Lichtenstein, Paul; Långström, Niklas

    2015-01-01

    Anabolic androgenic steroid (AAS) use is associated with aggressive and violent behaviour, but it remains uncertain if this relationship is causal in humans. We examined the link between AAS use and violent crime while controlling for polysubstance abuse and additional suggested risk factors for violence. Cross-sectional study of a population-based sample. In 2005, all Swedish-born male twins aged 20-47 years were invited to participate in the Swedish Twin Adults: Genes and Environment (STAGE) survey of the Swedish Twin Register (response rate = 60%). A total of 10,365 male survey participants with information on AAS use. Data on self-reported use of AAS, alcohol and other substances, attention deficit hyperactivity disorder (ADHD) and personality disorder symptoms were linked to nation-wide, longitudinal register information on criminal convictions, IQ, psychological functioning and childhood socio-economic status (SES) covariates. Any life-time use of AAS was associated strongly with conviction for a violent crime [2.7 versus 0.6% in convicted and non-convicted men, respectively; odds ratio (OR) = 5.0, 95% confidence interval (CI) = 2.7-9.3]. However, this link was substantially reduced and no longer significant when controlling for other substance abuse (OR = 1.6, 95% CI = 0.8-3.3). Controlling for IQ, psychological functioning, ADHD, personality disorder symptoms and childhood SES did not reduce the risk further. In the general population, co-occurring polysubstance abuse, but not IQ, other neuropsychological risks or socio-economic status, explains most of the relatively strong association between any anabolic androgenic steroid use and conviction for a violent crime. © 2014 Society for the Study of Addiction.

  14. Commentary: Synthetic Anabolic-Androgenic Steroids: A Plea for Controlled Substance Status.

    Science.gov (United States)

    Taylor, William N.

    1987-01-01

    The widespread abuse of synthetic anabolic-androgenic steriods, their habit-forming properties, and their other adverse effects are good reasons for reclassification of steriods as controlled substances under federal law, a step which may combat their abuse. (Author/CB)

  15. 17β-trenbolone, an anabolic–androgenic steroid as well as an environmental hormone, contributes to neurodegeneration

    International Nuclear Information System (INIS)

    Ma, Fucui; Liu, Daicheng

    2015-01-01

    Both genetic and environmental factors contribute to neurodegenerative disorders. In a large number of neurodegenerative diseases (for example, Alzheimer's disease (AD)), patients do not carry the mutant genes. Other risk factors, for example the environmental factors, should be evaluated. 17β-trenbolone is a kind of environmental hormone as well as an anabolic–androgenic steroid. 17β-trenbolone is used as a growth promoter for livestock in the USA. Also, a large portion of recreational exercisers inject 17β-trenbolone in large doses and for very long time to increase muscle and strength. 17β-trenbolone is stable in the environment after being excreted. In the present study, 17β-trenbolone was administered to adult and pregnant rats and the primary hippocampal neurons. 17β-trenbolone's distribution and its effects on serum hormone levels and Aβ42 accumulation in vivo and its effects on AD related parameters in vitro were assessed. 17β-trenbolone accumulated in adult rat brain, especially in the hippocampus, and in the fetus brain. It altered Aβ42 accumulation. 17β-trenbolone induced apoptosis of primary hippocampal neurons in vitro and resisted neuroprotective function of testosterone. Presenilin-1 protein expression was down-regulated while β-amyloid peptide 42 (Aβ42) production and caspase-3 activities were increased. Both androgen and estrogen receptors mediated the processes. 17β-trenbolone played critical roles in neurodegeneration. Exercisers who inject large doses of trenbolone and common people who are exposed to 17β-trenbolone by various ways are all influenced chronically and continually. Identification of such environmental risk factors will help us take early prevention measure to slow down the onset of neurodegenerative disorders. - Highlights: • The widely used anabolic–androgenic steroid 17β-trenbolone has neurotoxicity. • 17β-trenbolone crosses the blood brain barrier and placental barrier. • Rat has high level of

  16. 17β-trenbolone, an anabolic–androgenic steroid as well as an environmental hormone, contributes to neurodegeneration

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Fucui, E-mail: mafucui@hotmail.com [Wenzhou Institute of Biomaterials and Engineering, No. 16 Xinshan Road, Hi-tech Industry Park, Wenzhou (China); Key Laboratory of Animal Resistance, College of Life Science, Shandong Normal University, 88 East Wenhua Road, Jinan 250014 (China); Liu, Daicheng, E-mail: liudch@sdnu.edu.cn [Key Laboratory of Animal Resistance, College of Life Science, Shandong Normal University, 88 East Wenhua Road, Jinan 250014 (China)

    2015-01-01

    Both genetic and environmental factors contribute to neurodegenerative disorders. In a large number of neurodegenerative diseases (for example, Alzheimer's disease (AD)), patients do not carry the mutant genes. Other risk factors, for example the environmental factors, should be evaluated. 17β-trenbolone is a kind of environmental hormone as well as an anabolic–androgenic steroid. 17β-trenbolone is used as a growth promoter for livestock in the USA. Also, a large portion of recreational exercisers inject 17β-trenbolone in large doses and for very long time to increase muscle and strength. 17β-trenbolone is stable in the environment after being excreted. In the present study, 17β-trenbolone was administered to adult and pregnant rats and the primary hippocampal neurons. 17β-trenbolone's distribution and its effects on serum hormone levels and Aβ42 accumulation in vivo and its effects on AD related parameters in vitro were assessed. 17β-trenbolone accumulated in adult rat brain, especially in the hippocampus, and in the fetus brain. It altered Aβ42 accumulation. 17β-trenbolone induced apoptosis of primary hippocampal neurons in vitro and resisted neuroprotective function of testosterone. Presenilin-1 protein expression was down-regulated while β-amyloid peptide 42 (Aβ42) production and caspase-3 activities were increased. Both androgen and estrogen receptors mediated the processes. 17β-trenbolone played critical roles in neurodegeneration. Exercisers who inject large doses of trenbolone and common people who are exposed to 17β-trenbolone by various ways are all influenced chronically and continually. Identification of such environmental risk factors will help us take early prevention measure to slow down the onset of neurodegenerative disorders. - Highlights: • The widely used anabolic–androgenic steroid 17β-trenbolone has neurotoxicity. • 17β-trenbolone crosses the blood brain barrier and placental barrier. • Rat has high level of

  17. Mad men, women and steroid cocktails: a review of the impact of sex and other factors on anabolic androgenic steroids effects on affective behaviors.

    Science.gov (United States)

    Onakomaiya, Marie M; Henderson, Leslie P

    2016-02-01

    For several decades, elite athletes and a growing number of recreational consumers have used anabolic androgenic steroids (AAS) as performance enhancing drugs. Despite mounting evidence that illicit use of these synthetic steroids has detrimental effects on affective states, information available on sex-specific actions of these drugs is lacking. The focus of this review is to assess information to date on the importance of sex and its interaction with other environmental factors on affective behaviors, with an emphasis on data derived from non-human studies. The PubMed database was searched for relevant studies in both sexes. Studies examining AAS use in females are limited, reflecting the lower prevalence of use in this sex. Data, however, indicate significant sex-specific differences in AAS effects on anxiety-like and aggressive behaviors, interactions with other drugs of abuse, and the interplay of AAS with other environmental factors such as diet and exercise. Current methods for assessing AAS use have limitations that suggest biases of both under- and over-reporting, which may be amplified for females who are poorly represented in self-report studies of human subjects and are rarely used in animal studies. Data from animal literature suggest that there are significant sex-specific differences in the impact of AAS on aggression, anxiety, and concomitant use of other abused substances. These results have relevance for human females who take these drugs as performance-enhancing substances and for transgender XX individuals who may illicitly self-administer AAS as they transition to a male gender identity.

  18. Characteristics of Anabolic-Androgenic Steroid-Free Competitive Male and Female Bodybuilders.

    Science.gov (United States)

    Elliot, Diane L.; And Others

    1987-01-01

    Comparison of steroid-free male and female bodybuilders with sedentary controls and runners revealed that the bodybuilders had lower percentages of body fat. One-third of the female bodybuilders reported menstrual abnormalities. Lipid values of bodybuilders were comparable to a group of lean, aerobically trained athletes. (Author/CB)

  19. Steroids

    Science.gov (United States)

    ... return of symptoms and sometimes joint pain. SIDE EFFECTS Steroids can cause a wide range of unwanted effects. ... please talk with your doctor. MANAGING COMMON SIDE EFFECTS WEIGHT GAIN AND INCREASED BLOOD SUGAR LEVELS Steroids increase the appetite and often cause weight gain. ...

  20. Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

    Science.gov (United States)

    Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

    2010-01-01

    Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

  1. Analysis of anabolic androgenic steroids as sulfate conjugates using high performance liquid chromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Rzeppa, S; Heinrich, G; Hemmersbach, P

    2015-01-01

    Improvements in doping analysis can be effected by speeding up analysis time and extending the detection time. Therefore, direct detection of phase II conjugates of doping agents, especially anabolic androgenic steroids (AAS), is proposed. Besides direct detection of conjugates with glucuronic acid, the analysis of sulfate conjugates, which are usually not part of the routine doping control analysis, can be of high interest. Sulfate conjugates of methandienone and methyltestosterone metabolites have already been identified as long-term metabolites. This study presents the synthesis of sulfate conjugates of six commonly used AAS and their metabolites: trenbolone, nandrolone, boldenone, methenolone, mesterolone, and drostanolone. In the following these sulfate conjugates were used for development of a fast and easy analysis method based on sample preparation using solid phase extraction with a mixed-mode sorbent and detection by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Validation demonstrated the suitability of the method with regard to the criteria given by the technical documents of the World Anti-Doping Agency (WADA). In addition, suitability has been proven by successful detection of the synthesized sulfate conjugates in excretion urines and routine doping control samples. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Impact of Health Authority Control Measures Aimed at Reducing the Illicit Use of Anabolic-Androgenic Steroids.

    Science.gov (United States)

    Vázquez-Mourelle, Raquel; Carracedo-Martinez, Eduardo; Figueiras, Adolfo

    2018-01-01

    To evaluate two interventions on anabolic-androgenic-steroids (AAS) dispensation in retail pharmacies. The study was conducted in a north-western region of Spain. Data were the AAS supplied by wholesale drug distributors to retail pharmacies over a period of 102 months. It is designed as an ecological time-series study; the dependent variables were daily defined doses per 1,000 inhabitants per day of each drug. The two interventions evaluated were: (1) an inspection program intended for those retail pharmacies where there was an irregular dispensation and (2) a regulation put forth forcing these pharmacies to carry out additional registers. The medications studied were stanozolol, nandrolone, methenolone, testosterone and mesterolone. The pre-intervention use of AAS displayed a rising trend. There was an immediate reduction of 30.56% after the first intervention, and a further reduction of 35.25% after the second. There was a seasonal pattern of use in the pre-intervention period, pointing to an increased demand at the end of spring and beginning of summer. The most abused drugs were stanozolol and nandrolone. The health actions were very effective, in that they brought about a sharp reduction in the illicit use of AAS. These interventions could be applied to other drugs in which abuse were detected. © 2018 S. Karger AG, Basel.

  3. Exercise reinforcement, stress, and β-endorphins: an initial examination of exercise in anabolic-androgenic steroid dependence.

    Science.gov (United States)

    Hildebrandt, Tom; Shope, Sydney; Varangis, Eleanna; Klein, Diane; Pfaff, Donald W; Yehuda, Rachel

    2014-06-01

    Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Yuwei Wang

    2017-01-01

    Full Text Available The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR, are the main endocrine therapies for prostate cancer (PCa. But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability. The thoroughly validated QSAR model was used to virtually screen new dihydrotestosterones derivatives taken from PubChem, resulting in the finding of novel compounds CID_70128824, CID_70127147, and CID_70126881, whose in silico bioactivities are much higher than the published best one, even higher than bicalutamide. In addition, molecular docking, molecular dynamics (MD simulations, and MM/GBSA have been employed to analyze and compare the binding modes between the novel compounds and AR. Through the analysis of the binding free energy and residue energy decomposition, we concluded that the newly discovered chemicals can in silico bind to AR with similar position and mechanism to the reported active compound and the van der Waals interaction is the main driving force during the binding process.

  5. Steroids

    Science.gov (United States)

    ... Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Steroids KidsHealth ... athletes, and why not? It's fun to think about being the very best in your favorite sport, not to mention earning a big salary. But ...

  6. Steroids

    Science.gov (United States)

    ... of aggression and hostility Increased risk of heart disease, liver damage Addiction Read More about Steroids Be Informed. Search for information about a drug View Popular Searches: POT , HEROIN , METH Previous Pause Next Marijuana Featured Articles What You Should Know About Marijuana ...

  7. Acute aortic dissection in a young healthy athlete with androgenic anabolic steroid use: A case report

    Directory of Open Access Journals (Sweden)

    Barman M, Djamel B, Mathews J

    2014-07-01

    Full Text Available Background: Acute aortic dissection can occur at the time of intense physical exertion in strength-trained athletes like weight lifters, bodybuilders, throwers, and wrestlers. Rapid rise in blood pressure and history of hypertension are the most common causes of aortic dissection in athletes. It is a very tragic event because of its high mortality rate of about 32% in young patients. We report a case of aortic dissection in a young weightlifter with a history of anabolic steroid usage with an extensive intimal tear of the aorta at Sino tubular junction and arch. All athletes must be assessed for predisposing factors for aortic dissection, and all patients should be encouraged to undergo appropriate diagnostic studies, like echocardiography and blood pressure monitoring while weightlifting to recognize possible predisposing factors for aortic dissection. Athletes who do have a problem should be encouraged to avoid or limit their exercise or activity by their cardiologist. It is vital that this disastrous event be prevented in young people. In conclusion, although a rare occurrence, AD should be considered in symptomatic patients with any family history of early cardiac deaths, a history suggestive of a connective tissue disorder (that is, multiple joint surgeries or who practice weightlifting.

  8. Effect of androgenic-anabolic steroids and heavy strength training on patellar tendon morphological and mechanical properties.

    Science.gov (United States)

    Seynnes, Olivier R; Kamandulis, Sigitas; Kairaitis, Ramutis; Helland, Christian; Campbell, Emma-Louise; Brazaitis, Marius; Skurvydas, Albertas; Narici, Marco V

    2013-07-01

    Combined androgenic-anabolic steroids (AAS) and overloading affects tendon collagen metabolism and ultrastructure and is often associated with a higher risk of injury. The aim of this prospective study was to investigate whether such effects would be reflected in the patellar tendon properties of individuals with a history of long-term resistance training and AAS abuse (RTS group), compared with trained (RT) and untrained (CTRL) nonsteroids users. Tendon cross-sectional area (CSA), stiffness, Young's modulus, and toe limit strain were measured in vivo, from synchronized ultrasonography and dynamometry data. The patellar tendon of RT and RTS subjects was much stiffer and larger than in the CTRL group. However, stiffness and modulus were higher in the RTS group (26%, P < 0.05 and 30%, P < 0.01, respectively) than in the RT group. Conversely, tendon CSA was 15% (P < 0.05) larger in the RT group than in RTS, although differences disappeared when this variable was normalized to quadriceps maximal isometric torque. Yet maximal tendon stress was higher in RTS than in RT (15%, P < 0.05), without any statistical difference in maximal strain and toe limit strain between groups. The present lack of difference in toe limit strain does not substantiate the hypothesis of changes in collagen crimp pattern associated with AAS abuse. However, these findings indicate that tendon adaptations from years of heavy resistance training are different in AAS users, suggesting differences in collagen remodeling. Some of these adaptations (e.g., higher stress) could be linked to a higher risk of tendon injury.

  9. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Directory of Open Access Journals (Sweden)

    Dhananjay R Namjoshi

    Full Text Available Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE, a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS. How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  10. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Science.gov (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Carr, Michael; Martens, Kris M; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

    2016-01-01

    Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  11. A validated UHPLC-MS/MS method to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses.

    Science.gov (United States)

    Decloedt, Anneleen; Bailly-Chouriberry, Ludovic; Vanden Bussche, Julie; Garcia, Patrice; Popot, Marie-Agnes; Bonnaire, Yves; Vanhaecke, Lynn

    2015-06-01

    Doping control is a main priority for regulatory bodies of both the horse racing industry and the equestrian sports. Urine and blood samples are screened for the presence of hundreds of forbidden substances including anabolic-androgenic steroids (AASs). Based on the suspected endogenous origin of some AASs, with β-boldenone as the most illicit candidate, this study aimed to improve the knowledge of the naturally present AAS in horse urine. To this extent, a novel ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated according to the Association of Official Racing Chemists (AORC) and European Commission (EC) guidelines, proving the power of this new method. Low limits of detection (0.2 ng/mL), good reproducibility (percentage of standard deviation (%RSD)  0.99 and lack-of-fit analysis) were obtained for all included AASs. With this method, urine samples of 105 guaranteed untreated horses (47 geldings, 53 mares, and 5 stallions serving as a control) were screened for β-boldenone and five related natural steroids: androstadienedione (ADD), androstenedione (AED), alpha-testosterone (αT), beta-testosterone (βT), and progesterone (P). Progesterone, β-testosterone, and α-testosterone were detected in more than half of the horses at low concentrations (anabolic-androgenic steroids naturally present in urine of untreated horses (mares and geldings).

  12. Comparison of multiple linear regression, partial least squares and artificial neural networks for prediction of gas chromatographic relative retention times of trimethylsilylated anabolic androgenic steroids.

    Science.gov (United States)

    Fragkaki, A G; Farmaki, E; Thomaidis, N; Tsantili-Kakoulidou, A; Angelis, Y S; Koupparis, M; Georgakopoulos, C

    2012-09-21

    The comparison among different modelling techniques, such as multiple linear regression, partial least squares and artificial neural networks, has been performed in order to construct and evaluate models for prediction of gas chromatographic relative retention times of trimethylsilylated anabolic androgenic steroids. The performance of the quantitative structure-retention relationship study, using the multiple linear regression and partial least squares techniques, has been previously conducted. In the present study, artificial neural networks models were constructed and used for the prediction of relative retention times of anabolic androgenic steroids, while their efficiency is compared with that of the models derived from the multiple linear regression and partial least squares techniques. For overall ranking of the models, a novel procedure [Trends Anal. Chem. 29 (2010) 101-109] based on sum of ranking differences was applied, which permits the best model to be selected. The suggested models are considered useful for the estimation of relative retention times of designer steroids for which no analytical data are available. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men.

    Directory of Open Access Journals (Sweden)

    Hélène De Naeyer

    Full Text Available OBJECTIVE: The relationship between serum testosterone (T levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings. DESIGN: 677 men (25-45 years were recruited in a cross-sectional, population-based sibling pair study. METHODS: Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs, sex steroid levels (by LC-MS/MS, body composition (by DXA, muscle cross-sectional area (CSA (by pQCT, muscle force (isokinetic peak torque, grip strength and anthropometrics were studied using linear mixed-effect modelling. RESULTS: Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT and free T (FT levels were positively related to muscle CSA, whereas estradiol (E2 and free E2 (FE2 concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats. CONCLUSIONS: Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR

  14. Frequency of use, awareness, and attitudes toward side effects of anabolic-androgenic steroids consumption among male medical students in Iran.

    Science.gov (United States)

    Fayyazi Bordbar, Mohammad Reza; Abdollahian, Ebrahim; Samadi, Roya; Dolatabadi, Hamid

    2014-11-01

    This study was conducted to determine the frequency of anabolic-androgenic steroids consumption in male students studying at the university and their awareness, attitude, and role of sports activities; the present descriptive study was conducted on 271 volunteers in 2008. The data collected by self-report questionnaires was analyzed by descriptive inferential statistics. The prevalence of consumption was 3.3%, and it was significantly higher in those with a history of bodybuilding or athletic performance. The overall awareness rate was low, and the attitude was too optimistic. It seems that unawareness, incorrect attitude, and history of athletic performance increases the risk of consumption.

  15. Determination of selected endogenous anabolic androgenic steroids and ratios in urine by ultra high performance liquid chromatography tandem mass spectrometry and isotope pattern deconvolution.

    Science.gov (United States)

    Pitarch-Motellón, J; Sancho, J V; Ibáñez, M; Pozo, O; Roig-Navarro, A F

    2017-09-15

    An isotope dilution mass spectrometry (IDMS) method for the determination of selected endogenous anabolic androgenic steroids (EAAS) in urine by UHPLC-MS/MS has been developed using the isotope pattern deconvolution (IPD) mathematical tool. The method has been successfully validated for testosterone, epitestosterone, androsterone and etiocholanolone, employing their respective deuterated analogs using two certified reference materials (CRM). Accuracy was evaluated as recovery of the certified values and ranged from 75% to 108%. Precision was assessed in intraday (n=5) and interday (n=4) experiments, with RSDs below 5% and 10% respectively. The method was also found suitable for real urine samples, with limits of detection (LOD) and quantification (LOQ) below the normal urinary levels. The developed method meets the requirements established by the World Anti-Doping Agency for the selected steroids for Athlete Biological Passport (ABP) measurements, except in the case of androsterone, which is currently under study. Copyright © 2017. Published by Elsevier B.V.

  16. Identification of selected in vitro generated phase-I metabolites of the steroidal selective androgen receptor modulator MK-0773 for doping control purposes.

    Science.gov (United States)

    Lagojda, Andreas; Kuehne, Dirk; Krug, Oliver; Thomas, Andreas; Wigger, Tina; Karst, Uwe; Schänzer, Wilhelm; Thevis, Mario

    2016-01-01

    Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus. Besides the intended therapeutic use, SARMs have been found to be illicitly distributed and misused as doping agents in sport, necessitating frequently updated doping control analytical assays. As steroidal compounds reportedly undergo considerable metabolic transformations, the phase-I metabolism of MK-0773 was simulated using human liver microsomal (HLM) preparations and electrochemical conversion. Subsequently, major metabolic products were identified and characterized employing liquid chromatography-high-resolution/high- accuracy tandem mass spectrometry with electrospray (ESI) and atmospheric pressure chemical ionization (APCI) as well as nuclear magnetic resonance (NMR) spectroscopy. MK-0773 produced numerous phase-I metabolites under the chosen in vitro incubation reactions, mostly resulting from mono- and bisoxygenation of the steroid. HLM yielded at least 10 monooxygenated species, while electrochemistry-based experiments resulted predominantly in three monohydroxylated metabolites. Elemental composition data and product ion mass spectra were generated for these analytes, ESI/APCI measurements corroborated the formation of at least two N-oxygenated metabolites, and NMR data obtained from electrochemistry-derived products supported structures suggested for three monohydroxylated compounds. Hereby, the hydroxylation of the A-ring located N- bound methyl group was found to be of particular intensity. In the absence of controlled elimination studies, the

  17. Resistance training associated with the administration of anabolic-androgenic steroids improves insulin sensitivity in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Urtado CB

    2011-11-01

    Full Text Available Christiano Bertoldo Urtado1,2, Guilherme Borges Pereira3, Marilia Bertoldo Urtado4, Érica Blascovi de Carvalho2, Gerson dos Santos Leite1, Felipe Fedrizzi Donatto1, Claudio de Oliveira Assumpção1, Richard Diego Leite3, Carlos Alberto da Silva1, Marcelo Magalhães de Sales5, Ramires Alsamir Tibana5, Silvia Cristina Crepaldi Alves1, Jonato Prestes51Health Sciences, Methodist University of Piracicaba, Piracicaba, SP, 2Center for Investigation in Pediatrics, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, 3Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, 4Laboratory of Orofacial Pain, Division of Oral Physiology, Piracicaba Dental School, State University of Campinas, Campinas, SP, 5Graduation Program in Physical Education, Catholic University of Brasilia, Brasilia, DF, BrazilAbstract: The aim of the present study was to investigate the effects of anabolic-androgenic steroids and resistance training (RT on insulin sensitivity in ovariectomized rats. Adult female Wistar rats were divided into ten experimental groups (n = 5 animals per group: (1 sedentary (Sed-Intact; (2 sedentary ovariectomized (Sed-Ovx; (3 sedentary nandrolone (Sed-Intact-ND; (4 sedentary ovariectomized plus nandrolone (Sed-Ovx-ND; (5 trained (TR-Intact; (6 trained nandrolone (TR-Intact-ND; (7 trained ovariectomized (TR-Ovx; (8 trained ovariectomized plus nandrolone; (9 trained sham; and (10 trained ovariectomized plus sham. Four sessions of RT were used, during which the animals climbed a 1.1 m vertical ladder with weights attached to their tails. The sessions were performed once every 3 days, with between four and nine climbs and with eight to twelve dynamic movements per climb. To test the sensitivity of insulin in the pancreas, glucose and insulin tolerance tests were performed. For insulin sensitivity, there was a statistically significant interaction for the TR-Ovx group, which presented higher sensitivity

  18. Sport, and use of anabolic androgenic steroids among Icelandic high school students: a critical test of three perspectives.

    Science.gov (United States)

    Thorlindsson, Thorolfur; Halldorsson, Vidar

    2010-12-20

    This study investigates the use of anabolic androgenic steroids (AAS) among a national representative sample of high school students in Iceland. We test several hypotheses drawn from three perspectives. The first perspective focuses on the use of AAS as an individual phenomenon motivated by the desire to succeed in sport. The second perspective views the use of AAS as shaped by norms and values embedded in social relationships of formally organized sport. The third perspective suggests that factors outside sport, which have been shown to correlate with the use of other substances, predict the use of AAS. We use logistic regression and predicted probabilities to analyze data from a national representative survey of 11,031 Icelandic high school students. Our results indicated that the use of AAS is not significantly related to participation in formally organized sports. However, it positively relates to fitness and physical training in informal contexts. We found a relatively strong relationship between the use of AAS and the use of illicit substances and a moderate relationship between AAS use and alcohol and tobacco consumption. We also found a significant negative relationship between AAS use and school integration and school achievement, and a significant positive relationship between AAS use and school anomie. The relation between AAS use and family-related variables was weaker. Finally, we found that the relationship between sport participation, physical exercise, and AAS use varies across levels of anomie and integration. Our findings suggest that the use of AAS and especially illegal substances should be considered more as a social and a health problem rather than a sport specific issue. We found that high school students participating in fitness and informal training outside of formally organized sport clubs are the main risk group and should be the target of prevention efforts. However, this should not be done at the expense of general risk factors that

  19. Use of anabolic androgenic steroids produces greater oxidative stress responses to resistance exercise in strength-trained men

    Directory of Open Access Journals (Sweden)

    Hamid Arazi

    Full Text Available The aim of this study was to determine the effect of anabolic androgenic steroids (AAS use on oxidative stress responses to a single session of resistance exercise in strength-trained men. Twenty-three strength trained men, with 11 self-reporting regular AAS use and 12 self-reporting never taking AAS (NAAS volunteered to participate in this study. Blood draws were obtained pre and post resistance exercise in order to evaluate changes in oxidative stress biomarkers levels (i.e., 8-hydroxy-2-deoxyguanosine [8-OHdG], malondialdehyde [MDA], and nitric oxide [NO], antioxidant defense systems (i.e., glutathione peroxidase [GPx] and catalase [CAT], and glucose (GLU levels. The AAS users had higher level of 8-OHdG (77.3 ± 17 vs. 57.7 ± 18.2 ng/mg, MDA (85.6 ± 17.8 vs. 52.3 ± 15.1 ng/mL, and GPx (9.1 ± 2.3 vs. 7.1 ± 1.3 mu/mL compared to NAAS at pre exercise (p < 0.05. Both the experimental groups showed increases in 8-OHdG (p = 0.001, MDA (p = 0.001, GPx (p = 0.001, NO (p = 0.04, CAT (p = 0.02 and GLU (p = 0.001 concentrations after resistance exercise, and the AAS group indicated significant differences in 8-OHdG (p = 0.02 and MDA (p = 0.05 concentrations compared with NAAS users at post exercise. In conclusion, use of AAS is associated with alterations in immune function resulting in oxidative stress, and cell damage; however, high-intensity resistance exercise could increase greater oxidative stress biomarkers in strength-trained men. Keywords: ROS, Strength exercise, Anabolic

  20. Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

    International Nuclear Information System (INIS)

    Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi

    2016-01-01

    Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d_5-Girard reagent P (d_5-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones related

  1. Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi, E-mail: yqfeng@whu.edu.cn

    2016-01-28

    Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d{sub 5}-Girard reagent P (d{sub 5}-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones

  2. Potentially harmful advantage to athletes: a putative connection between UGT2B17 gene deletion polymorphism and renal disorders with prolonged use of anabolic androgenic steroids

    Directory of Open Access Journals (Sweden)

    Barker James

    2010-04-01

    Full Text Available Abstract Background and objective With prolonged use of anabolic androgenic steroids (AAS, occasional incidents of renal disorders have been observed. Independently, it has also been established that there are considerable inter-individual and inter-ethnic differences, in particular with reference to the uridine diphosphate-glucuronosyltransferase 2B17 (UGT2B17 gene, in metabolising these compounds. This report postulates the association of deletion polymorphism in the UGT2B17 gene with the occurrence of renal disorders on chronic exposure to AAS. Presentation of the hypothesis The major deactivation and elimination pathway of AASs is through glucuronide conjugation, chiefly catalyzed by the UGT2B17 enzyme, followed by excretion in urine. Excretion of steroids is affected in individuals with a deletion mutation in the UGT2B17 gene. We hypothesize that UGT2B17 deficient individuals are more vulnerable to developing renal disorders with prolonged use of AAS owing to increases in body mass index and possible direct toxic effects of steroids on the kidneys. Elevated serum levels of biologically active steroids due to inadequate elimination can lead to prolonged muscle build up. An increase in body mass index may cause renal injuries due to sustained elevated glomerular pressure and flow rate. Testing the hypothesis In the absence of controlled clinical trials in humans, observational studies can be carried out. Real time PCR with allelic discrimination should be employed to examine the prevalence of different UGT2B17 genotypes in patients with impaired renal function and AAS abuse. In individuals with the UGT2B17 deletion polymorphism, blood tests, biofluid analyses, urinalysis, and hair analyses following the administration of an anabolic steroid can be used to determine the fate of the substance once in the body. Implications of the hypothesis If the hypothesis is upheld, anabolic steroid users with a deletion mutation in the UGT2B17 gene may be

  3. Effects of Anabolic Androgenic Steroids on the Reproductive System of Athletes and Recreational Users: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Christou, Maria A; Christou, Panagiota A; Markozannes, Georgios; Tsatsoulis, Agathocles; Mastorakos, George; Tigas, Stelios

    2017-09-01

    Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system. This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users. An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation. Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation

  4. UDP-glucuronyltransferase-catalyzed deconjugation of bilirubin monoglucuronide

    NARCIS (Netherlands)

    Cuypers, H. T.; ter Haar, E. M.; Jansen, P. L.

    1984-01-01

    Bilirubin monoglucuronide is rapidly deconjugated when incubated with UDP and rat liver microsomal preparations at pH 5.1. The following evidence was found that this reaction is catalyzed by UDP-glucuronyltransferase: (i) unconjugated bilirubin and UDP-glucuronic acid were identified as the reaction

  5. Simultaneous ionization and analysis of 84 anabolic androgenic steroids in human urine using liquid chromatography-silver ion coordination ionspray/triple-quadrupole mass spectrometry.

    Science.gov (United States)

    Kim, So-Hee; Cha, Eun-Ju; Lee, Kang Mi; Kim, Ho Jun; Kwon, Oh-Seung; Lee, Jaeick

    2014-01-01

    Metal ion coordination ionspray (M(+) CIS) ionization is a powerful technique to enhance ionization efficiency and sensitivity. In this study, we developed and validated an analytical method for simultaneous ionization and analysis of 84 anabolic androgenic steroids (65 exogenous and 19 endogenous) using liquid chromatography-silver ion coordination ionspray/triple-quadrupole mass spectrometry (LC-Ag(+) CIS/MS/MS). The concentrations of silver ions and organic solvents have been optimized to increase the amount of silver ion coordinated complexes. A combination of 25 μM of silver ions and methanol showed the best sensitivity. The validation results showed the intra- (0.8-9.2%) and inter-day (2.5-14.9%) precisions, limits of detection (0.0005-5.0 ng/mL), and matrix effect (71.8-100.3%) for the screening analysis. No significant ion suppression was observed. In addition, this method was successfully applied to analysis of positive samples from suspected abusers and useful for the detection of the trace levels of anabolic steroids in human urine samples. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Effect of long-term treatment with steroid hormones or tamoxifen on the progesterone receptor and androgen receptor in the endometrium of ovariectomized cynomolgus macaques

    Directory of Open Access Journals (Sweden)

    Cline J Mark

    2003-02-01

    Full Text Available Abstract The progesterone receptor (PR and androgen receptor (AR belong to the nuclear receptor superfamily. Two isoforms of PR (A and B have been identified with different functions. The expression of AR, each isoform of PR and their involvement in long-term effects on the endometrium after hormonal replacement therapy (HRT or tamoxifen (TAM treatment is not known. The aims of this study were to determine PR(A+B, PRB and AR distribution by immunohistochemistry in the macaque (Macaca fascicularis endometrium. Ovariectomized (OVX animals were orally treated continuously for 35 months with either conjugated equine estrogens (CEE; medroxyprogesterone acetate (MPA; the combination of CEE/MPA; or TAM. Treatment with CEE/MPA tended to down-regulate PR in the superficial glands, but increased it in the stroma. TAM treatment increased both the PR and PRB levels in the stroma. Overall, less than 20% of the cells were positive for the PRB isoform and less variation was observed after steroid treatment. AR was found in the stroma, mainly distributed in the basal layer of the endometrium in the OVX and steroid treated groups, but was absent in the TAM treated group. No AR was found in the glandular epithelium. The present data show that long-term hormone treatment affects the PR level, and also the ratio between PRA and PRB in the endometrium.

  7. New Insights on Steroid Biotechnology

    DEFF Research Database (Denmark)

    Fernandez-Cabezon, Lorena; Galán, Beatriz; García, José L.

    2018-01-01

    Nowadays steroid manufacturing occupies a prominent place in the pharmaceutical industry with an annual global market over $10 billion. The synthesis of steroidal active pharmaceutical ingredients (APIs) such as sex hormones (estrogens, androgens, and progestogens) and corticosteroids is currentl...

  8. Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

    Science.gov (United States)

    Max, S. R.; Rance, N.

    1983-01-01

    The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

  9. Accurate quantification of endogenous androgenic steroids in cattle's meat by gas chromatography mass spectrometry using a surrogate analyte approach

    International Nuclear Information System (INIS)

    Ahmadkhaniha, Reza; Shafiee, Abbas; Rastkari, Noushin; Kobarfard, Farzad

    2009-01-01

    Determination of endogenous steroids in complex matrices such as cattle's meat is a challenging task. Since endogenous steroids always exist in animal tissues, no analyte-free matrices for constructing the standard calibration line will be available, which is crucial for accurate quantification specially at trace level. Although some methods have been proposed to solve the problem, none has offered a complete solution. To this aim, a new quantification strategy was developed in this study, which is named 'surrogate analyte approach' and is based on using isotope-labeled standards instead of natural form of endogenous steroids for preparing the calibration line. In comparison with the other methods, which are currently in use for the quantitation of endogenous steroids, this approach provides improved simplicity and speed for analysis on a routine basis. The accuracy of this method is better than other methods at low concentration and comparable to the standard addition at medium and high concentrations. The method was also found to be valid according to the ICH criteria for bioanalytical methods. The developed method could be a promising approach in the field of compounds residue analysis

  10. GC-MS quantitative analysis of black market pharmaceutical products containing anabolic androgenic steroids seized by the Brazilian Federal Police.

    Science.gov (United States)

    Neves, Diana Brito da Justa; Caldas, Eloisa Dutra

    2017-06-01

    The use of counterfeit or substandard medicines can have an important health impact, resulting in therapeutic failure, be toxic or even cause death. Anabolic steroids are a frequent target for counterfeiters worldwide, being the second most frequent counterfeited class in Brazil. The aims of this work were to optimize and validate a GC-MS method for the quantitative determination of anabolic steroids in tablet, aqueous suspension and oil solution forms, and to analyze pharmaceutical products sent to Brazilian Federal Police (BFP) for forensic analysis. Sample preparation included extraction with methanol in ultrasonic bath followed by centrifugation. The method was successfully validated and 345 samples of pharmaceutical products were analyzed (328 medicines and 17 dietary supplements). About 42% of the medicines were counterfeits, 28.7% of tablets, 12.0% of suspensions and 65.2% of oil solutions; 11% were considered substandards. Five dietary supplements contained undeclared anabolic steroids, including two containing methandrostenolone at 5.4 and 5.8mg/capsule, equivalent to levels found in medicines. The proposed method is suitable for implementation in routine analysis for identification of counterfeits and substandard products. The analytical results show the need to raise awareness of consumers over the risks from the consumption of anabolic steroids from the clandestine market and for more incisive actions from government agencies aiming at decreasing the availability of these products. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Effects of cypermethrin on the ligand-independent interaction between androgen receptor and steroid receptor coactivator-1

    International Nuclear Information System (INIS)

    Pan, Chen; Liu, Ya-Peng; Li, Yan-Fang; Hu, Jin-Xia; Zhang, Jin-Peng; Wang, Hong-Mei; Li, Jing; Xu, Li-Chun

    2012-01-01

    The pyrethroid insecticide, cypermethrin has been considered as an environmental anti-androgen by interfering with the androgen receptor (AR) transactivation. In order to clarify the effects of cypermethrin on the ligand-independent interaction between the AR and SRC-1, the mammalian two-hybrid assay has been developed in the study. The AR N-terminal domain 1–660 amino acid residues were subcloned into the plasmid pVP16 to construct the vector pVP16-ARNTD. The SRC-1 C-terminal domain 989–1240 amino acid residues were subcloned into the plasmid pM to construct the vector pM-SRC-1. The fusion vectors pVP16-ARNTD, pM-SRC-1 and the pG5CAT Reporter Vector were cotransfected into the CV-1 cells. The AR AF1 interacted with SRC-1 in the absence of exogenous ligand 5α-dihydrotestosterone (DHT). Furthermore, DHT did not enhance the interaction between AR AF-1 and SRC-1 at the concentrations from 10 −10 M to 10 −8 M. Cypermethrin inhibited the interaction between the AR AF1 and SRC-1, and the significant reduction was detected at the concentration of 10 −5 M. It is suggested that the interaction between the AR AF1 and SRC-1 is ligand-independent. Cypermethrin inhibits AR activity by disrupting the ligand-independent AR–SRC-1 interaction.

  12. The Misuse of Anabolic-Androgenic Steroids among Iranian Recreational Male Body-Builders and Their Related Psycho-Socio-Demographic factors.

    Science.gov (United States)

    Angoorani, Hooman; Halabchi, Farzin

    2015-12-01

    The high prevalence and potential side effects of anabolic-androgenic steroids (AAS) misuse by athletes has made it a major public health concern. Epidemiological studies on the abuse of such drugs are mandatory for developing effective preventive drug control programs in sports community. This study aimed to investigate the prevalence of AAS abuse and their association with some psycho-socio-demographic factors in Iranian male recreational body-builders. Between March and October 2011; 906 recreational male body-builders from 103 randomly selected bodybuilding clubs in Tehran, Iran were participated in this study. Some psycho-socio- demographic factors including age, job, average family income, family size, sport experience (months), weekly duration of the sporting activity (h), purpose of participation in sporting activity, mental health as well as body image (via General Health Questionnaire and Multidimensional Body-Self Relations Questionnaire, respectively), and history of AAS use were obtained by interviews using questionnaires. Participants were all recreational male body-builders [mean age (SD): 25.7 (7.1), ranging 14-56 yr]. Self-report of AAS abuse was registered in 150 body-builders (16.6%). Among different psycho-socio-demographic factors, only family income and sport experience were inversely associated with AAS abuse. Lifetime prevalence of AAS abuse is relatively high among recreational body-builders based on their self-report. Some psycho-socio-demographic factors including family income and sport experience may influence the prevalence of AAS abuse.

  13. Serca2a and Na(+)/Ca(2+) exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid.

    Science.gov (United States)

    Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco; Silva, Josiane Fernandes da; Lemos, Virgínia Soares; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza

    2016-06-15

    Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20mg/kg/week for 4weeks); and NDE (trained and treated). The haemodynamic parameters (+dP/dtmax, -dP/dtmin and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na(+)/Ca(2+) exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Screening for exogenous androgen anabolic steroids in human hair by liquid chromatography/orbitrap-high resolution mass spectrometry

    International Nuclear Information System (INIS)

    Strano-Rossi, Sabina; Castrignanò, Erika; Anzillotti, Luca; Odoardi, Sara; De-Giorgio, Fabio; Bermejo, Ana; Pascali, Vincenzo L.

    2013-01-01

    Graphical abstract: -- Highlights: •LC–HRMS screening method for the detection of a variety of anabolics in hair. •Detection of unmetabolized anabolic steroids and their esters in hair matrix by simple keratin pretreatment. •Identification of target compounds by retention time, accurate mass and isotopic cluster. •Quantitative determination of detected compounds. •Possibility to a retrospective re-analysis of the acquired datafile in case a further analyte is to be screened. -- Abstract: A method for the screening of various anabolic steroids and their esters in human hair, based on liquid-chromatography–high resolution mass spectrometry using an Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This method involved methanolic incubation of 30 mg of hair and analysis of the relevant extract in HPLC using a C18 column. The mass detector, with nominal resolving power of 100,000, operated in full scan mode in APCI under positive ionization mode. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times. The limits of detection obtained varied from 10 to 50 pg mg −1 , and limits of quantitation were 0.5 ng mg −1 for all compounds. The method was linear for all analytes in the ranges from the LOQ to 6 ng mg −1 , giving correlation coefficients >0.99 for all analytes. Also accuracy (intended as %E) and repeatability (%CV) were always lower than 15%. Specificity was assessed by analysing ten blank samples and fifteen samples from polidrug abusers. This method was applied to a real-life case, resulting in the identification of testosterone undecanoate in the hair of a suspect. The analyte identity was confirmed by the analysis of its in-source fragmentation and comparison to a certified standard. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened

  15. Screening for exogenous androgen anabolic steroids in human hair by liquid chromatography/orbitrap-high resolution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Strano-Rossi, Sabina, E-mail: sabina.stranorossi@rm.unicatt.it [Institute of Legal Medicine, Catholic University of Sacred Heart, L.go F. Vito, 1, 00168 Rome (Italy); Castrignanò, Erika; Anzillotti, Luca; Odoardi, Sara; De-Giorgio, Fabio [Institute of Legal Medicine, Catholic University of Sacred Heart, L.go F. Vito, 1, 00168 Rome (Italy); Bermejo, Ana [Institute of Legal Medicine, University of Santiago de Compostela, Av S. Francisco s/n, Santiago de Compostela (Spain); Pascali, Vincenzo L. [Institute of Legal Medicine, Catholic University of Sacred Heart, L.go F. Vito, 1, 00168 Rome (Italy)

    2013-09-02

    Graphical abstract: -- Highlights: •LC–HRMS screening method for the detection of a variety of anabolics in hair. •Detection of unmetabolized anabolic steroids and their esters in hair matrix by simple keratin pretreatment. •Identification of target compounds by retention time, accurate mass and isotopic cluster. •Quantitative determination of detected compounds. •Possibility to a retrospective re-analysis of the acquired datafile in case a further analyte is to be screened. -- Abstract: A method for the screening of various anabolic steroids and their esters in human hair, based on liquid-chromatography–high resolution mass spectrometry using an Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This method involved methanolic incubation of 30 mg of hair and analysis of the relevant extract in HPLC using a C18 column. The mass detector, with nominal resolving power of 100,000, operated in full scan mode in APCI under positive ionization mode. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times. The limits of detection obtained varied from 10 to 50 pg mg{sup −1}, and limits of quantitation were 0.5 ng mg{sup −1} for all compounds. The method was linear for all analytes in the ranges from the LOQ to 6 ng mg{sup −1}, giving correlation coefficients >0.99 for all analytes. Also accuracy (intended as %E) and repeatability (%CV) were always lower than 15%. Specificity was assessed by analysing ten blank samples and fifteen samples from polidrug abusers. This method was applied to a real-life case, resulting in the identification of testosterone undecanoate in the hair of a suspect. The analyte identity was confirmed by the analysis of its in-source fragmentation and comparison to a certified standard. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened.

  16. Bile salt deconjugation and cholesterol removal from media by Lactobacillus strains used as probiotics in chickens.

    Science.gov (United States)

    Ramasamy, Kalavathy; Abdullah, Norhani; Wong, Michael Cvl; Karuthan, Chinna; Ho, Yin Wan

    2010-01-15

    Bile salt deconjugation by Lactobacillus strains is often closely linked to bile tolerance and survival of the strains in the gut and lowering of cholesterol in the host. The present study investigated the deconjugation of bile salts and removal of cholesterol by 12 Lactobacillus strains in vitro. The 12 strains were previously isolated from the gastrointestinal tract of chickens. The 12 Lactobacillus strains could deconjugate sodium glycocholate (GCA, 16.87-100%) and sodium taurocholate (TCA, 1.69-57.43%) bile salts to varying degrees, with all strains except L. salivarius I 24 having a higher affinity for GCA. The 12 Lactobacillus strains also showed significant (P strains (C1, C10 and C16) and between cholesterol removal and deconjugation of TCA (r = 0.38) and GCA (r = 0.70) among the L. brevis strains (I 12, I 23, I 25, I 211 and I 218). In contrast, although L. gallinarum I 16 and I 26 and L. panis C 17 showed high deconjugating activity, there was no correlation between cholesterol removal and deconjugation of bile salts in these strains. The results showed that the 12 Lactobacillus strains were able to deconjugate bile salts and remove cholesterol in vitro, but not all strains with high deconjugating activity removed cholesterol effectively. Copyright (c) 2009 Society of Chemical Industry.

  17. Screening for exogenous androgen anabolic steroids in human hair by liquid chromatography/orbitrap-high resolution mass spectrometry.

    Science.gov (United States)

    Strano-Rossi, Sabina; Castrignanò, Erika; Anzillotti, Luca; Odoardi, Sara; De-Giorgio, Fabio; Bermejo, Ana; Pascali, Vincenzo L

    2013-09-02

    A method for the screening of various anabolic steroids and their esters in human hair, based on liquid-chromatography-high resolution mass spectrometry using an Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This method involved methanolic incubation of 30 mg of hair and analysis of the relevant extract in HPLC using a C18 column. The mass detector, with nominal resolving power of 100,000, operated in full scan mode in APCI under positive ionization mode. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times. The limits of detection obtained varied from 10 to 50 pg mg(-1), and limits of quantitation were 0.5 ng mg(-1) for all compounds. The method was linear for all analytes in the ranges from the LOQ to 6 ng mg(-1), giving correlation coefficients >0.99 for all analytes. Also accuracy (intended as %E) and repeatability (%CV) were always lower than 15%. Specificity was assessed by analysing ten blank samples and fifteen samples from polidrug abusers. This method was applied to a real-life case, resulting in the identification of testosterone undecanoate in the hair of a suspect. The analyte identity was confirmed by the analysis of its in-source fragmentation and comparison to a certified standard. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Sex and Exercise Interact to Alter the Expression of Anabolic Androgenic Steroid-Induced Anxiety-Like Behaviors in the Mouse

    Science.gov (United States)

    Onakomaiya, Marie M.; Porter, Donna M.; Oberlander, Joseph G.; Henderson, Leslie P.

    2014-01-01

    Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala. PMID:24768711

  19. Potential of atmospheric pressure chemical ionization source in gas chromatography tandem mass spectrometry for the screening of urinary exogenous androgenic anabolic steroids.

    Science.gov (United States)

    Raro, M; Portolés, T; Pitarch, E; Sancho, J V; Hernández, F; Garrostas, L; Marcos, J; Ventura, R; Segura, J; Pozo, O J

    2016-02-04

    The atmospheric pressure chemical ionization (APCI) source for gas chromatography-mass spectrometry analysis has been evaluated for the screening of 16 exogenous androgenic anabolic steroids (AAS) in urine. The sample treatment is based on the strategy currently applied in doping control laboratories i.e. enzymatic hydrolysis, liquid-liquid extraction (LLE) and derivatization to form the trimethylsilyl ether-trimethylsilyl enol ether (TMS) derivatives. These TMS derivatives are then analyzed by gas chromatography tandem mass spectrometry using a triple quadrupole instrument (GC-QqQ MS/MS) under selected reaction monitoring (SRM) mode. The APCI promotes soft ionization with very little fragmentation resulting, in most cases, in abundant [M + H](+) or [M + H-2TMSOH](+) ions, which can be chosen as precursor ions for the SRM transitions, improving in this way the selectivity and sensitivity of the method. Specificity of the transitions is also of great relevance, as the presence of endogenous compounds can affect the measurements when using the most abundant ions. The method has been qualitatively validated by spiking six different urine samples at two concentration levels each. Precision was generally satisfactory with RSD values below 25 and 15% at the low and high concentration level, respectively. Most the limits of detection (LOD) were below 0.5 ng mL(-1). Validation results were compared with the commonly used method based on the electron ionization (EI) source. EI analysis was found to be slightly more repeatable whereas lower LODs were found for APCI. In addition, the applicability of the developed method has been tested in samples collected after the administration of 4-chloromethandienone. The highest sensitivity of the APCI method for this compound, allowed to increase the period in which its administration can be detected. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Serca2a and Na+/Ca2+ exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

    International Nuclear Information System (INIS)

    Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco; Silva, Josiane Fernandes da; Lemos, Virgínia Soares; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza

    2016-01-01

    Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt max , − dP/dt min and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na + /Ca 2+ exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.

  1. Anabolic androgenic steroids--use and correlates among gym users--an assessment study using questionnaires and observations at gyms in the Stockholm region.

    Science.gov (United States)

    Leifman, Håkan; Rehnman, Charlotta; Sjöblom, Erika; Holgersson, Stefan

    2011-07-01

    The purpose of this study was to estimate the prevalence of anabolic androgenic steroid (AAS) use and offers to use among gym users in Stockholm County (Sweden), and to conduct a comparison of concordance in estimates of AAS and supplements at gyms between two data collection methods. A questionnaire was distributed to members at 36 training facilities and 1,752 gym users participated in the study. An observation study was conducted as covert participant observations at 64 gyms. According to the questionnaire, 3.9% of men reported life time use of AAS, 1.4% use during the past 12 months and 0.4% AAS use during past 30 days. Not only were there similar patterns found in the two methods, i.e., similar age and gender distributions for AAS use, but analyses of concordance showed that gyms with a higher prevalence of self-reported AAS-use and supplement use (questionnaire) showed a significantly higher proportion of observer-assessed AAS users. Analyses of individual predictors showed that AAS users were almost always young men, regular weight trainers and more often users of drugs and nutritional supplements. The higher prevalence of AAS use among gym users than in the general population makes the former an appropriate target group for AAS prevention. The connection between supplements, drugs and AAS use suggests that effective AAS prevention need to focus on several risk factors for AAS use. The clear resemblance in estimates between the observation and questionnaire data strengthen the credibility of the two methods.

  2. Usage and perceptions of anabolic-androgenic steroids among male fitness centre attendees in Kuwait--a cross-sectional study.

    Science.gov (United States)

    Alsaeed, Ibrahim; Alabkal, Jarrah R

    2015-08-22

    Considering the recent popularity of bodybuilding and the apparent spread of anabolic androgenic steroid (AAS) use amongst bodybuilding enthusiasts in Kuwait, there is a relative lack of scientific investigation into the use, knowledge and attitudes towards AAS amongst the population at risk of abusing it. Therefore, this study aims to investigate the frequency, knowledge, attitudes and practice of AAS use amongst male fitness centre attendees in Kuwait. A cross sectional survey utilizing a self-administered questionnaire was used. Information on demographics as well as knowledge and attitude about and towards the use of AAS was included in the questionnaire. Ten fitness centres in Kuwait were randomly selected and questionnaires were distributed to all individuals leaving each centre on randomly selected days and periods of time for each centre. Overall n = 400 questionnaires were distributed. A total of n = 194 questionnaires were returned completed (~49%). Of the responders, 22.7% used AAS. The 19-25 age group had the highest occurrence (46.8%) of first-time AAS use. In contrast with non-users, most (70.5%) of AAS users believed that having an optimally muscular body can only be achieved by using AAS, and a small minority (6.8%) believed that AAS usage would have significant harms to health. Only 18.2% of AAS users had appropriate knowledge regarding the side effects of AAS. Non-users were as much uninformed as AAS users regarding the side effects of AAS. The usage of AAS is high amongst male gym users in Kuwait and is likely to present an additional burden to the health service. An effective initiative to minimize the burden of AAS abuse should focus on changing the attitudes towards AAS rather than spreading awareness of their side effects.

  3. The Misuse of Anabolic-Androgenic Steroids among Iranian Recreational Male Body-Builders and Their Related Psycho-Socio-Demographic factors

    Science.gov (United States)

    ANGOORANI, Hooman; HALABCHI, Farzin

    2015-01-01

    Background: The high prevalence and potential side effects of anabolic-androgenic steroids (AAS) misuse by athletes has made it a major public health concern. Epidemiological studies on the abuse of such drugs are mandatory for developing effective preventive drug control programs in sports community. This study aimed to investigate the prevalence of AAS abuse and their association with some psycho-socio-demographic factors in Iranian male recreational body-builders. Methods: Between March and October 2011; 906 recreational male body-builders from 103 randomly selected bodybuilding clubs in Tehran, Iran were participated in this study. Some psycho-socio- demographic factors including age, job, average family income, family size, sport experience (months), weekly duration of the sporting activity (h), purpose of participation in sporting activity, mental health as well as body image (via General Health Questionnaire and Multidimensional Body-Self Relations Questionnaire, respectively), and history of AAS use were obtained by interviews using questionnaires. Results: Participants were all recreational male body-builders [mean age (SD): 25.7 (7.1), ranging 14–56 yr]. Self-report of AAS abuse was registered in 150 body-builders (16.6%). Among different psycho-socio-demographic factors, only family income and sport experience were inversely associated with AAS abuse. Conclusion: Lifetime prevalence of AAS abuse is relatively high among recreational body-builders based on their self-report. Some psycho-socio-demographic factors including family income and sport experience may influence the prevalence of AAS abuse. PMID:26811817

  4. Detection of anabolic steroids in dietary supplements: The added value of an androgen yeast bioassay in parallel with a liquid chromatography-tandem mass spectrometry screening method

    NARCIS (Netherlands)

    Rijk, J.C.W.; Bovee, T.F.H.; Wang, S.; Poucke, C.; Peteghem, van C.; Nielen, M.W.F.

    2009-01-01

    Recently we constructed a recombinant yeast cell that expresses the human androgen receptor (hAR) and yeast enhanced green fluorescent protein (yEGFP), the latter in response to androgens. When exposed to testosterone, the concentration where half-maximal activation is reached (EC50) was 50 nM.

  5. Development of Androgen- and Estrogen-Responsive bio-assays, members of a panel of human cell line-based highly selective steroid-responsive bioassays

    NARCIS (Netherlands)

    Sonneveld, E.; Jansen, H.J.

    2004-01-01

    We have established highly sensitive and specific androgen and estrogen reporter cell lines which we have named AR (androgen receptor) and ERα (estrogen receptor alpha) CALUX® (Chemically Activated LUciferase eXpression), respectively. Both bioassays are member of a panel of CALUX reporter cell

  6. Development of androgen-and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays

    NARCIS (Netherlands)

    Sonneveld, E.; Jansen, H.J..; Riteco, J.A.C.; Brouwer, A.

    2005-01-01

    We have established highly sensitive and specific androgen and estrogen reporter cell lines which we have named AR (androgen receptor) and ERα (estrogen receptor alpha) CALUX® (Chemically Activated LUciferase eXpression), respectively. Both bioassays are member of a panel of CALUX reporter cell

  7. Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study

    Science.gov (United States)

    Selmer, Christian; Østergren, Peter Busch; Pedersen, Karen Boje; Schou, Morten; Gustafsson, Finn; Faber, Jens; Juul, Anders; Kistorp, Caroline

    2016-01-01

    Aims Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers. Methods This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18–50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. Results Former AAS abusers exhibited significantly lower median (25th –75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9–17.7) nmol/l vs. 18.8 (16.6–22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05). Conclusions Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation

  8. Potential of atmospheric pressure chemical ionization source in gas chromatography tandem mass spectrometry for the screening of urinary exogenous androgenic anabolic steroids

    International Nuclear Information System (INIS)

    Raro, M.; Portolés, T.; Pitarch, E.; Sancho, J.V.; Hernández, F.; Garrostas, L.; Marcos, J.; Ventura, R.; Segura, J.; Pozo, O.J.

    2016-01-01

    The atmospheric pressure chemical ionization (APCI) source for gas chromatography-mass spectrometry analysis has been evaluated for the screening of 16 exogenous androgenic anabolic steroids (AAS) in urine. The sample treatment is based on the strategy currently applied in doping control laboratories i.e. enzymatic hydrolysis, liquid–liquid extraction (LLE) and derivatization to form the trimethylsilyl ether-trimethylsilyl enol ether (TMS) derivatives. These TMS derivatives are then analyzed by gas chromatography tandem mass spectrometry using a triple quadrupole instrument (GC-QqQ MS/MS) under selected reaction monitoring (SRM) mode. The APCI promotes soft ionization with very little fragmentation resulting, in most cases, in abundant [M + H] + or [M + H-2TMSOH] + ions, which can be chosen as precursor ions for the SRM transitions, improving in this way the selectivity and sensitivity of the method. Specificity of the transitions is also of great relevance, as the presence of endogenous compounds can affect the measurements when using the most abundant ions. The method has been qualitatively validated by spiking six different urine samples at two concentration levels each. Precision was generally satisfactory with RSD values below 25 and 15% at the low and high concentration level, respectively. Most the limits of detection (LOD) were below 0.5 ng mL −1 . Validation results were compared with the commonly used method based on the electron ionization (EI) source. EI analysis was found to be slightly more repeatable whereas lower LODs were found for APCI. In addition, the applicability of the developed method has been tested in samples collected after the administration of 4-chloromethandienone. The highest sensitivity of the APCI method for this compound, allowed to increase the period in which its administration can be detected. - Highlights: • APCI source has been evaluated for the screening of 16 exogenous AAS in urine. • Suitable precision was

  9. Detection of anabolic and androgenic steroids and/or their esters in horse hair using ultra-high performance liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Kwok, Karen Y; Choi, Timmy L S; Kwok, Wai Him; Wong, Jenny K Y; Wan, Terence S M

    2017-04-14

    Anabolic and androgenic steroids (AASs) are a class of prohibited substances banned in horseracing at all times. The common approach for controlling the misuse of AASs in equine sports is by detecting the presence of AASs and/or their metabolites in urine and blood samples using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). This approach, however, often falls short as the duration of effect for many AASs are longer than their detection time in both urine and blood. As a result, there is a high risk that such AASs could escape detection in their official race-day samples although they may have been used during the long period of training. Hair analysis, on the other hand, can afford significantly longer detection windows. In addition, the identification of synthetic ester derivatives of AASs in hair, particularly for the endogenous ones, can provide unequivocal proof of their exogenous origin. This paper describes the development of a sensitive method (at sub to low parts-per-billion or ppb levels) for detecting 48 AASs and/or their esters in horse hair using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Decontaminated horse hair was pulverised and subjected to in-situ liquid-liquid extraction in a mixture of hexane - ethyl acetate (7:3, v/v) and phosphate buffer (0.1M, pH 9.5), followed by additional clean-up using mixed-mode solid-phase extraction. The final extract was analysed using UHPLC-HRMS in the positive electrospray ionisation (ESI) mode with both full scan and parallel reaction monitoring (PRM). This method was validated for qualitative identification purposes. Validation data, including method specificity, method sensitivity, extraction recovery, method precision and matrix effect are presented. Method applicability was demonstrated by the successful detection and confirmation of testosterone propionate in a referee hair sample. To our knowledge, this was

  10. Potential of atmospheric pressure chemical ionization source in gas chromatography tandem mass spectrometry for the screening of urinary exogenous androgenic anabolic steroids

    Energy Technology Data Exchange (ETDEWEB)

    Raro, M.; Portolés, T.; Pitarch, E.; Sancho, J.V.; Hernández, F. [Research Institute for Pesticides and Water, University Jaume I, E-12071 Castellón (Spain); Garrostas, L. [Bioanalysis Research Group, IMIM, Hospital del Mar Medical Research Institute, Doctor Aiguader 88, 08003 Barcelona (Spain); Marcos, J.; Ventura, R.; Segura, J. [Bioanalysis Research Group, IMIM, Hospital del Mar Medical Research Institute, Doctor Aiguader 88, 08003 Barcelona (Spain); Department of Experimental and Health Sciencies, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona (Spain); Pozo, O.J., E-mail: opozo@imim.es [Bioanalysis Research Group, IMIM, Hospital del Mar Medical Research Institute, Doctor Aiguader 88, 08003 Barcelona (Spain)

    2016-02-04

    The atmospheric pressure chemical ionization (APCI) source for gas chromatography-mass spectrometry analysis has been evaluated for the screening of 16 exogenous androgenic anabolic steroids (AAS) in urine. The sample treatment is based on the strategy currently applied in doping control laboratories i.e. enzymatic hydrolysis, liquid–liquid extraction (LLE) and derivatization to form the trimethylsilyl ether-trimethylsilyl enol ether (TMS) derivatives. These TMS derivatives are then analyzed by gas chromatography tandem mass spectrometry using a triple quadrupole instrument (GC-QqQ MS/MS) under selected reaction monitoring (SRM) mode. The APCI promotes soft ionization with very little fragmentation resulting, in most cases, in abundant [M + H]{sup +} or [M + H-2TMSOH]{sup +} ions, which can be chosen as precursor ions for the SRM transitions, improving in this way the selectivity and sensitivity of the method. Specificity of the transitions is also of great relevance, as the presence of endogenous compounds can affect the measurements when using the most abundant ions. The method has been qualitatively validated by spiking six different urine samples at two concentration levels each. Precision was generally satisfactory with RSD values below 25 and 15% at the low and high concentration level, respectively. Most the limits of detection (LOD) were below 0.5 ng mL{sup −1}. Validation results were compared with the commonly used method based on the electron ionization (EI) source. EI analysis was found to be slightly more repeatable whereas lower LODs were found for APCI. In addition, the applicability of the developed method has been tested in samples collected after the administration of 4-chloromethandienone. The highest sensitivity of the APCI method for this compound, allowed to increase the period in which its administration can be detected. - Highlights: • APCI source has been evaluated for the screening of 16 exogenous AAS in urine. • Suitable

  11. Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Jon Jarløv Rasmussen

    Full Text Available Abuse of anabolic androgenic steroids (AAS is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers.This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI elapsed duration since AAS cessation: 2.5 (1.7; 3.7 years and 30 healthy control participants. All participants were aged 18-50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction were recorded systematically.Former AAS abusers exhibited significantly lower median (25th -75th percentiles total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7 nmol/l vs. 18.8 (16.6-22.0 nmol/l (P < 0.01. Overall, 27.2% (13.3; 45.5 of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l whereas no control participants exhibited testosterone below this limit (P < 0.01. Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01. The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2% (11.1; 42.2, erectile dysfunction ((27.3% (13.3; 45.6 and decreased libido ((40.1% (23.2; 57.0 than the other two groups (trend analyses: P < 0.05.Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely decreased AMH

  12. Androgen Receptor Signaling in Bladder Cancer

    OpenAIRE

    Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

    2017-01-01

    Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in u...

  13. Discovery and therapeutic promise of selective androgen receptor modulators.

    Science.gov (United States)

    Chen, Jiyun; Kim, Juhyun; Dalton, James T

    2005-06-01

    Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects.

  14. Neuroprotection of Sex Steroids

    Science.gov (United States)

    Liu, Mingyue; Kelley, Melissa H.; Herson, Paco S.; Hurn, Patricia D.

    2011-01-01

    Sex steroids are essential for reproduction and development in animals and humans, and sex steroids also play an important role in neuroprotection following brain injury. New data indicate that sex-specific responses to brain injury occur at the cellular and molecular levels. This review summarizes the current understanding of neuroprotection by sex steroids, particularly estrogen, androgen, and progesterone, based on both in vitro and in vivo studies. Better understanding of the role of sex steroids under physiological and pathological conditions will help us to develop novel effective therapeutic strategies for brain injury. PMID:20595940

  15. Pharmacology of anabolic steroids.

    Science.gov (United States)

    Kicman, A T

    2008-06-01

    Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

  16. Urine testing for designing steroids by liquid chromatography and androgen bioaasay detection and electrospray quadrupole time-of-flight mass spectrometry identification

    NARCIS (Netherlands)

    Nielen, M.W.F.; Bovee, T.F.H.; Engelen, M.C.; Rutgers, P.; Hamers, A.R.M.; Rhijn, van J.A.; Hoogenboom, L.A.P.

    2006-01-01

    New anabolic steroids show up occasionally in sports doping and in veterinary control. The discovery of these designer steroids is facilitated by findings of illicit preparations, thus allowing bioactivity testing, structure elucidation using NMR and mass spectrometry, and final incorporation in

  17. Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia.

    Science.gov (United States)

    Dessein, P H; Shipton, E A; Joffe, B I; Hadebe, D P; Stanwix, A E; Van der Merwe, B A

    1999-11-01

    Neuroendocrine deficiencies have been implicated in fibromyalgia (FM). In the present study, adrenal androgen metabolites and their relationship with health status in FM were investigated. For comparison, serum levels of other implicated neuroendocrine mediators were correlated with health status. Fifty-seven consecutive women with FM completed the Fibromyalgia Impact Questionnaire (FIQ). Fasting blood samples were taken for measurement of dehydroepiandrosterone sulphate (DHEAS), free testosterone (T), cortisol, serotonin and insulin-like growth factor-1. Normal value for DHEAS and T were obtained from 114 controls. DHEAS levels were decreased significantly in pre- and postmenopausal patients (PBMI correlated positively with pain (PBMI, the correlation between age adjusted DHEAS and pain was no longer significant. Hyposecretion of adrenal androgens was documented in FM. This was more pronounced in obese patients. Low serum androgen levels correlated with poor health status in FM. Longitudinal studies are needed to elucidate whether these are cause and/or effect relationships.

  18. Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents

    Directory of Open Access Journals (Sweden)

    Abdulla A-B Badawy

    2018-02-01

    Full Text Available Modulation of tryptophan (Trp metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS and associated image and performance enhancers. Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO inhibition and enhancement of serotonin function. Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines. Exercise and excessive protein and branched-chain amino acid intakes may aggravate the effects of large AAS dosage. The hypothesis is testable in humans and experimental animals by measuring parameters of Trp metabolism and disposition and related metabolic processes.

  19. Efeitos dos esteroides anabólicos androgênicos sobre o útero e parâmetros reprodutivos de ratas adultas Effects of androgenic anabolic steroids on the uterus and reproductive parameters of adult female rats

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Cherici Camargo

    2009-09-01

    normal male rats for reproductive parameters evaluation, composing the groups treated during the pre-gestational period. Another group of 20 female rats were treated during the gestational period (7th-14th days. For data analysis, the Kruskal-Wallis non-parametric variance analysis was used, followed by the test of Dunn or of Student-Newman-Keus (5% significance level. RESULTS: there was a significant body weight increase in the androgenized females (ND: 305±50; T: 280±35; ND+T: 275±30 versus C: 255±22 g; p<0.05. Uterine weight was not affected by the steroidal treatment (ND: 0.6±0.2; T: 0.4±0.04; ND+T: 0.7±0.1 versus C: 0.4±0.09 g. All the androgenized females presented estral acyclicity and endometrium characterized by papilliferous luminal lining, oedematous stroma with hemorrhagic areas and secretory activity. There were changes in the morphometrical thickness parameters of the luminal epithelium, myometrium and perimetrium in the androgenized groups. None of the female rats got pregnant when treated with steroids in the pre-gestational period and the treatment during organogenesis affected negatively the reproductive parameters. CONCLUSIONS: steroidal agents alter the uterine structure and impair fertility and gestational outcome in female rats.

  20. Nonprescription steroids on the Internet.

    Science.gov (United States)

    Clement, Christen L; Marlowe, Douglas B; Patapis, Nicholas S; Festinger, David S; Forman, Robert F

    2012-02-01

    This study evaluated the degree to which anabolic-androgenic steroids are proffered for sale over the Internet and how they are characterized on popular Web sites. Searches for specific steroid product labels (e.g., Dianabol) between March 2006 and June 2006 revealed that approximately half of the Web sites advocated their "safe" use, and roughly one third offered to sell them without prescriptions. The Web sites frequently presented misinformation about steroids and minimized their dangers. Less than 5% of the Web sites presented accurate health risk information about steroids or provided information to abusers seeking to discontinue their steroid use. Implications for education, prevention, treatment, and policy are discussed.

  1. Steroid implants and markers of bone turnover in steers

    African Journals Online (AJOL)

    jannes

    Steroidal implants are used extensively in beef cattle management to take ... The practice of administering androgenic and estrogenic steroid implants to increase lean .... ELISA in bovine serum, so the assay was validated in our laboratory.

  2. Specific characterization of non-steroidal selective androgen peceptor modulators using supercritical fluid chromatography coupled to ion-mobility mass spectrometry: application to the detection of enobosarm in bovine urine.

    Science.gov (United States)

    Beucher, Laure; Dervilly-Pinel, Gaud; Cesbron, Nora; Penot, Mylène; Gicquiau, Audrey; Monteau, Fabrice; Le Bizec, Bruno

    2017-02-01

    Currently under development for therapeutic purposes in human medicine, non-steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth associated pathways. As such, they present a potential for abuse in sports and food-producing animals as interesting alternative anabolic substances. Forbidden since 2008 by the World Anti-Doping Agency (WADA) these compounds are however easily available and could be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies have to be developed for specific and sensitive detection of these compounds in biological matrices. Using an innovative analytical platform constituted of supercritical fluid chromatography coupled to ion mobility-mass spectrometry, the present study enabled efficient separation and identification in urine of 4 of these drugs (andarine, bicalutamide, hydroxyflutamide, and enobosarm) in accordance with European Union criteria (Commission Decision 2002/657/EC). Besides providing information about compounds structure and behaviour in gas phase, such a coupling enabled reaching low limits of detection (LOD < 0.05 ng.mL -1 for andarine and limits of detection < 0.005 ng.mL -1 for the three others) in urine with good repeatability (CV < 21 %). The workflow has been applied to quantitative determination of enobosarm elimination in urine of treated bovine (200 mg, oral). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Molecular mechanisms of androgen receptor functions

    NARCIS (Netherlands)

    K. Steketee (Karine)

    2007-01-01

    textabstractThe androgens testosterone (T) and dihydrotestosterone (DHT) are steroid hormones, which are necessary for development and maintenance of the functions of the male sex organs, including the prostate. Androgens also play an important role in benign abnormalities of the prostate and in the

  4. Accurate quantification of endogenous androgenic steroids in cattle's meat by gas chromatography mass spectrometry using a surrogate analyte approach

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadkhaniha, Reza; Shafiee, Abbas [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174 (Iran, Islamic Republic of); Rastkari, Noushin [Center for Environmental Research, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Kobarfard, Farzad [Department of Medicinal Chemistry, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tavaneer Ave., Valieasr St., Tehran (Iran, Islamic Republic of)], E-mail: farzadkf@yahoo.com

    2009-01-05

    Determination of endogenous steroids in complex matrices such as cattle's meat is a challenging task. Since endogenous steroids always exist in animal tissues, no analyte-free matrices for constructing the standard calibration line will be available, which is crucial for accurate quantification specially at trace level. Although some methods have been proposed to solve the problem, none has offered a complete solution. To this aim, a new quantification strategy was developed in this study, which is named 'surrogate analyte approach' and is based on using isotope-labeled standards instead of natural form of endogenous steroids for preparing the calibration line. In comparison with the other methods, which are currently in use for the quantitation of endogenous steroids, this approach provides improved simplicity and speed for analysis on a routine basis. The accuracy of this method is better than other methods at low concentration and comparable to the standard addition at medium and high concentrations. The method was also found to be valid according to the ICH criteria for bioanalytical methods. The developed method could be a promising approach in the field of compounds residue analysis.

  5. Taurocholate Deconjugation and Cholesterol Binding by Indigenous Dadih Lactic Acid Bacteria

    Directory of Open Access Journals (Sweden)

    USMAN PATO

    2005-09-01

    Full Text Available High serum cholesterol levels have been associated with an increased risk for human coronary heart disease. Lowering of serum cholesterol has been suggested to prevent the heart disease. To reduce serum cholesterol levels one may consumed diet supplementat of fermented dairy product such as dadih. Lactic acid bacteria present in dadih may alter serum cholesterol by directly bind to dietary cholesterol and/or deconjugation of bile salts. Acid and bile tolerance, deconjugation of sodium taurocholate, and the cholesterol-binding ability of lactic acid bacteria from dadih were examined. Among ten dadih lactic acid bacteria tested, six strains namely I-11, I-2775, K-5, I-6257, IS-7257, and B-4 could bind cholesterol and deconjugate sodium taurocholate. However, the last four strains were very sensitive to bile. Therefore, Lactobacillus fermentum I-11 and Leuconostoc lactis subsp. lactis I-2775 those were tolerant to acid and oxgall (bile and deconjugated sodium taurocholate and bound cholesterol could be recommended as probiotic to prevent coronary heart disease.

  6. Sex steroids and neurogenesis.

    Science.gov (United States)

    Heberden, Christine

    2017-10-01

    The brain has long been known as a dimorphic organ and as a target of sex steroids. It is also a site for their synthesis. Sex steroids in numerous ways can modify cerebral physiology, and along with many processes adult neurogenesis is also modulated by sex steroids. This review will focus on the effects of the main steroids, estrogens, androgens and progestogens, and unveil some aspects of their partly disclosed mechanisms of actions. Gonadal steroids act on different steps of neurogenesis: cell proliferation seems to be increased by estrogens only, while androgens and progestogens favor neuronal renewal by increasing cell survival; differentiation is a common target. Aging is characterized by a cognitive deficiency, paralleled by a decrease in the rate of neuronal renewal and in the levels of circulating gonadal hormones. Therefore, the effects of gonadal hormones on the aging brain are important to consider. The review will also be expanded to related molecules which are agonists to the nuclear receptors. Sex steroids can modify adult neuronal renewal and the extensive knowledge of their actions on neurogenesis is essential, as it can be a leading pathway to therapeutic perspectives. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Determination of two progestin metabolites (17α-hydroxypregnanolone and pregnanediol) and different classes of steroids (androgens, estrogens, corticosteroids, progestins) in rivers and wastewaters by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

    Science.gov (United States)

    Zhang, Kun; Fent, Karl

    2018-01-01

    A highly sensitive and robust method was developed for routine analysis of two progestin metabolites, 17α-hydroxypregnanolone (17OH-Δ5P) and pregnanediol (PD), and 31 other natural and synthetic steroids and related metabolites (estrogens, androgens, corticosteroids, progestins) in river water, as well as influents and effluents of municipal wastewater treatment plants (WWTP) using HPLC-MS/MS combined with solid-phase extraction. For the various matrixes considered, the optimized method showed satisfactory performance with recoveries of 70-120% for most of target steroids. The method detection limits (MDLs) ranged from 0.01 to 3ng/L for river water, 0.02 to 10ng/L for WWTP effluents, and 0.1 to 40ng/L for influents with good linearity and reproducibility. The developed method was successfully applied for the analysis of steroids in rivers and WWTP influent and effluents. WWTP influents concentrations of 17OH-Δ5P and PD were 51-256ng/L and up to 400ng/L, respectively, along with androstenedione (concentration range: 38-220ng/L), testosterone (11-26ng/L), estrone (2.3-37ng/L), 17β-estradiol (N.D.-8.7ng/L), 17α-hydroxyprogesterone (N.D.-66ng/L), medroxyprogesterone acetate (N.D.-5.3ng/L), and progesterone (2.0-22ng/L), while only androstenedione (ADD), estrone (E1), and estriol (E3) were detected in effluent with concentrations ranging up to 1.7ng/L, 0.90ng/L and 0.8ng/L, respectively. In river water samples, only ADD and E1 were detected with concentrations up to 1.0ng/L and 0.91ng/L. Our procedure represents the first method for analyzing 17OH-Δ5P and PD in environmental samples along with a large series of steroids. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors.

    Science.gov (United States)

    Wu, Yue; Godoy, Alejandro; Azzouni, Faris; Wilton, John H; Ip, Clement; Mohler, James L

    2013-09-01

    Blocking 5α-reductase-mediated testosterone conversion to dihydrotestosterone (DHT) with finasteride or dutasteride is the driving hypothesis behind two prostate cancer prevention trials. Factors affecting intracellular androgen levels and the androgen receptor (AR) signaling axis need to be examined systematically in order to fully understand the outcome of interventions using these drugs. The expression of three 5α-reductase isozymes, as determined by immunohistochemistry and qRT-PCR, was studied in five human prostate cancer cell lines. Intracellular testosterone and DHT were analyzed using mass spectrometry. A luciferase reporter assay and AR-regulated genes were used to evaluate the modulation of AR activity. Prostate cancer cells were capable of accumulating testosterone to a level 15-50 times higher than that in the medium. The profile and expression of 5α-reductase isozymes did not predict the capacity to convert testosterone to DHT. Finasteride and dutasteride were able to depress testosterone uptake in addition to lowering intracellular DHT. The inhibition of AR activity following drug treatment often exceeded the expected response due to reduced availability of DHT. The ability to maintain high intracellular testosterone might compensate for the shortage of DHT. The biological effect of finasteride or dutasteride appears to be complex and may depend on the interplay of several factors, which include testosterone turnover, enzymology of DHT production, ability to use testosterone and DHT interchangeably, and propensity of cells for off-target AR inhibitory effect. © 2013 Wiley Periodicals, Inc.

  9. In vitro simulation of the equine hindgut as a tool to study the influence of phytosterol consumption on the excretion of anabolic-androgenic steroids in horses.

    Science.gov (United States)

    Decloedt, A I; Bailly-Chouriberry, L; Vanden Bussche, J; Garcia, P; Popot, M-A; Bonnaire, Y; Vanhaecke, L

    2015-08-01

    Traditionally, steroids other than testosterone are considered to be synthetic, anabolic steroids. Nevertheless, in stallions, it has been shown that β-Bol can originate from naturally present testosterone. Other precursors, including phytosterols from feed, have been put forward to explain the prevalence of low levels of steroids (including β-Bol and ADD) in urine of mares and geldings. However, the possible biotransformation and identification of the precursors has thus far not been investigated in horses. To study the possible endogenous digestive transformation, in vitro simulations of the horse hindgut were set up, using fecal inocula obtained from eight different horses. The functionality of the in vitro model was confirmed by monitoring the formation of short-chain fatty acids and the consumption of amino acids and carbohydrates throughout the digestion process. In vitro digestion samples were analyzed with a validated UHPLC-MS/MS method. The addition of β-Bol gave rise to the formation of ADD (androsta-1,4-diene-3,17-dione) or αT. Upon addition of ADD to the in vitro digestions, the transformation of ADD to β-Bol was observed and this for all eight horses' inocula, in line with previously obtained in vivo results, again confirming the functionality of the in vitro model. The transformation ratio proved to be inoculum and thus horse dependent. The addition of pure phytosterols (50% β-sitosterol) or phytosterol-rich herbal supplements on the other hand, did not induce the detection of β-Bol, only low concentrations of AED, a testosterone precursor, could be found (0.1 ng/mL). As such, the digestive transformation of ADD could be linked to the detection of β-Bol, and the consumption of phytosterols to low concentrations of AED, but there is no direct link between phytosterols and β-Bol. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Automated and sensitive determination of four anabolic androgenic steroids in urine by online turbulent flow solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry: a novel approach for clinical monitoring and doping control.

    Science.gov (United States)

    Guo, Feng; Shao, Jing; Liu, Qian; Shi, Jian-Bo; Jiang, Gui-Bin

    2014-07-01

    A novel method for automated and sensitive analysis of testosterone, androstenedione, methyltestosterone and methenolone in urine samples by online turbulent flow solid-phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry was developed. The optimization and validation of the method were discussed in detail. The Turboflow C18-P SPE column showed the best extraction efficiency for all the analytes. Nanogram per liter (ng/L) level of AAS could be determined directly and the limits of quantification (LOQs) were 0.01 ng/mL, which were much lower than normally concerned concentrations for these typical anabolic androgenic steroids (AAS) (0.1 ng/mL). The linearity range was from the LOQ to 100 ng/mL for each compound, with the coefficients of determination (r(2)) ranging from 0.9990 to 0.9999. The intraday and interday relative standard deviations (RSDs) ranged from 1.1% to 14.5% (n=5). The proposed method was successfully applied to the analysis of urine samples collected from 24 male athletes and 15 patients of prostate cancer. The proposed method provides an alternative practical way to rapidly determine AAS in urine samples, especially for clinical monitoring and doping control. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Inhaled Steroids

    Science.gov (United States)

    ... considerations when your dosage changes. What about side effects and inhaled steroids? The most common side effects with inhaled steroids ... inhaled steroid has much less potential for side effects than steroid pills or syrups. There have been concerns regarding ...

  12. Esteróides anabólicos androgênicos e sua relação com a prática desportiva Anabolic androgenic steroids and the relation to the sportive practice

    Directory of Open Access Journals (Sweden)

    Tatiana Sousa Cunha

    2004-06-01

    Full Text Available Os esteróides anabólicos androgênicos (EAA são um grupo de compostos naturais e sintéticos formados a partir da testosterona ou um de seus derivados, cuja indicação terapêutica clássica está associada a situações de hipogonadismo e quadros de deficiência do metabolismo protéico. Atuando sobre os receptores androgênicos, modulam de forma indissociável tanto os efeitos androgênicos como os anabólicos. Tais substâncias variam na relação entre a atividade anabólica: androgênica, mas nenhum fármaco atualmente disponível é capaz de desencadear somente efeitos anabólicos. O primeiro relato da utilização dos EAA com o objetivo de melhorar o desempenho atlético ocorreu em 1954, na Áustria, e, desde então, esta prática tornou-se amplamente difundida. Obviamente, o uso de EAA está fora dos limites competitivos e foi declarado ilegal pelos setores governamentais desportivos nacionais e internacionais. Entretanto, segundo estatísticas do Comitê Olímpico Internacional, realizadas em 2000, os EAA são o grupo de substâncias ergogênicas mais comumente utilizadas no processo de doping. Estudos mostram que altas doses de EAA podem acarretar vários efeitos adversos como atrofia do tecido testicular, tumores hepáticos e de próstata, alterações hepatocelulares, no metabolismo lipídico, de humor e de comportamento. O objetivo do presente trabalho será compilar os dados a respeito dos EAA, envolvendo as perspectivas históricas acerca do tema, a fisiologia e os tipos de EAA atualmente existentes, suas indicações terapêuticas e efeitos adversos resultantes do uso indiscriminado bem como a relação entre o uso de EAA e melhora da performance atlética.Anabolic androgenic steroids (AAS are a group of natural and synthetic agents formed from testosterone or one of its derivatives, whose classical therapeutic indications are associated to hipogonadism and deficiency of proteic metabolism. Acting on androgenic receptors

  13. Androgen Receptor Signaling in Bladder Cancer

    Science.gov (United States)

    Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

    2017-01-01

    Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. PMID:28241422

  14. Androgen Receptor Signaling in Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-02-01

    Full Text Available Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer.

  15. Sudden cardiac arrest following ventricular fibrillation attributed to anabolic steroid use in an adolescent.

    Science.gov (United States)

    Lichtenfeld, Jana; Deal, Barbara J; Crawford, Susan

    2016-06-01

    Anabolic androgenic steroids are synthetic derivatives of testosterone that promote the growth of skeletal muscles and have many recognised cardiovascular effects. We report the clinical presentation and pathological findings of an adolescent male whose sudden cardiac arrest following ventricular fibrillation was attributed to anabolic androgenic steroid use. The age of our patient reflects the usage of anabolic androgenic steroids among younger athletes and highlights the need for increased awareness among practitioners.

  16. Effects of the dietary amount and source of protein, resistance training and anabolic-androgenic steroids on body weight and lipid profile of rats.

    Science.gov (United States)

    Aparicio, V A; Sánchez, C; Ortega, F B; Nebot, E; Kapravelou, G; Porres, J M; Aranda, P

    2013-01-01

    Dietary protein amount and source, hypertrophy resistance training (RT) and anabolicandrogenic steroids (AAS) may affect body weight and plasma and hepatic lipid profile. 157 adult male Wistar rats were randomly distributed in 16 experimental groups resulting in: normal-protein (NP) or high-protein (HP) diets, whey or soy-protein diets, with or without RT and with or without AAS, for 3 months. Final body weight was lower in the RT and AAS groups compared to sedentary and non- AAS groups, respectively (all, pweight of rats that performed RT or ingested a HP diet (all, p<0.05). HDL-cholesterol was higher when RT was combined with HP diets (p=0.010) or non-AAS and when HP diets were combined with non-AAS (both,p<0.001). Groups that combined RT with non-AAS administration obtained the lowest hepatic TAG (p<0.05). Among all the interventions tested, AAS was the factor that most negatively affected plasma and hepatic lipid profile, whereas HP diets and RT could benefit lipid profile, especially when combined. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  17. Morbidade hospitalar por ingestão de esteroides anabólico-androgênicos (EAA no Brasil Hospital morbidity due to anabolic-androgenic steroids (AAS consumption in Brazil

    Directory of Open Access Journals (Sweden)

    Sérgio Henrique Almeida da Silva Junior

    2013-04-01

    ária de 15-29 anos possuíram as maiores taxas no período estudado.INTRODUCTION: Anabolic androgenic steroids (AAS are male sex hormones, developers and maintainers of sexual characteristics associated with masculinity and the anabolic status of somatic tissues. The physical and mental effects of AAS abuse are rare and it is almost impossible to say with certainty what adverse effects may become evident after their self-administration; however, they constitute risk of death for the individuals. OBJECTIVE: The aim of this study was to describe the main characteristics of morbidity by AAS ingestion in Brazil in the 2000/2010 period. METHODS: Information on hospitalizations was obtained from computerized databases of the Ministry of Health. In the analysis of AAS consumption as primary or secondary diagnosis for hospital admission, the E28.1 (androgen excess, E34.5 (androgen insensitivity syndrome, T38.7 (adverse effect of and underdosing of androgens and anabolic congeners and Y42.7 (adverse effects in the therapeutic use of androgens and anabolic congeners codes of the ICD-10 were used. RESULTS: Hospitalizations by AAS were responsible for 0.001% of total admissions in the country. 1,319 admissions (mean = 119.9, SD = 99.01 were accounted. The Androgen insensitivity syndrome was the primary cause, corresponding to 55.8% of total admissions. Of of all hospitalizations, 1% of patients died and the maximum stay was of 47 days (mean = 3.8, SD = 4.7. Minas Gerais, Maranhão and Espírito Santo presented the highest rates of hospital admissions per 1,000,000 inhabitants from 2002 to 2007. Women and people aged 15-29 presented the highest hospitalization rate 82.5% and 37.7%, respectively. CONCLUSION: The results of this study showed that the hospitalization rate was relatively low for AAS intake; women and individuals aged 15-29 years possessed the highest rates in the period studied.

  18. Sundhedspolitik på steroider

    DEFF Research Database (Denmark)

    Christiansen, Ask Vest

    2012-01-01

    Danmark er det land i verden der har valgt den måske mest drastiske metode til bekæmpelse af brug af anabole androgene steroider (AAS) i fitness- og styrketræningsmiljøerne. Ikke pga. oplysningskampagnerne, samarbejdet med SKAT eller at AAS er ulovlige. Der hvor Danmark skiller sig ud er ved brugen...

  19. Steroid profiling in doping analysis

    NARCIS (Netherlands)

    Kerkhof, Daniël Henri van de

    2001-01-01

    Profiling androgens in urine samples is used in doping analysis for the detection of abused steroids of endogenous origin. These profiling techniques were originally developed for the analysis of testosterone, mostly by means of the ratio of testosterone to epitestosterone (T/E ratio). A study was

  20. Serca2a and Na{sup +}/Ca{sup 2+} exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco [Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo (Brazil); Silva, Josiane Fernandes da; Lemos, Virgínia Soares [Department of Physiology and Biophysic, Federal University of Minas Gerais, Minas Gerais (Brazil); Andrade, Tadeu Uggere de [Department of Pharmacy, University Vila Velha, Vila Velha, Espirito Santo (Brazil); Bissoli, Nazaré Souza, E-mail: nazarebissoli@gmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo (Brazil)

    2016-06-15

    Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt{sub max}, − dP/dt{sub min} and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na{sup +}/Ca{sup 2+} exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.

  1. Anabolic steroid induced hypogonadism in young men.

    Science.gov (United States)

    Coward, Robert M; Rajanahally, Saneal; Kovac, Jason R; Smith, Ryan P; Pastuszak, Alexander W; Lipshultz, Larry I

    2013-12-01

    The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered. We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy. Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, panabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Selective androgen receptor modulators: in pursuit of tissue-selective androgens.

    Science.gov (United States)

    Omwancha, Josephat; Brown, Terry R

    2006-10-01

    The androgen receptor mediates the androgenic and anabolic activity of the endogenous steroids testosterone and 5alpha-dihydrotestosterone. Current knowledge of the androgen receptor protein structure, and the molecular mechanisms surrounding the binding properties and activities of agonists and antagonists has led to the design and development of novel nonsteroidal ligands with selected tissue-specific androgen receptor agonist and antagonist activities. The activity of these compounds, termed selective androgen receptor modulators (SARMs), is directed toward the maintenance or enhancement of anabolic effects on bone and muscle with minimal androgenic effects on prostate growth. SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.

  3. Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals

    DEFF Research Database (Denmark)

    Körner, Wolfgang; Vinggaard, Anne; Terouanne, B.

    2004-01-01

    steroidal androgens, two antiandrogens, an androgenic control, 5alpha-dihydrotestosterone (DHT), and an antiandrogenic control, bicalutamide (ICI 176,334). All laboratories correctly detected the androgenic activity of 4-androsten-3,17-dione and 17alpha-methyl-testosterone. For both compounds...

  4. In Vitro Androgen Bioassays as a Detection Method for Designer Androgens

    Directory of Open Access Journals (Sweden)

    Alison K. Heather

    2013-02-01

    Full Text Available Androgens are the class of sex steroids responsible for male sexual characteristics, including increased muscle mass and decreased fat mass. Illicit use of androgen doping can be an attractive option for those looking to enhance sporting performance and/or physical appearance. The use of in vitro bioassays to detect androgens, especially designer or proandrogens, is becoming increasingly important in combating androgen doping associated with nutritional supplements. The nutritional sports supplement market has grown rapidly throughout the past decade. Many of these supplements contain androgens, designer androgens or proandrogens. Many designer or proandrogens cannot be detected by the standard highly-sensitive screening methods such as gas chromatography-mass spectrometry because their chemical structure is unknown. However, in vitro androgen bioassays can detect designer and proandrogens as these assays are not reliant on knowing the chemical structure but instead are based on androgen receptor activation. For these reasons, it may be advantageous to use routine androgen bioassay screening of nutraceutical samples to help curb the increasing problem of androgen doping.

  5. Effects of bile salt deconjugation by probiotic strains on the survival of antibiotic-resistant foodborne pathogens under simulated gastric conditions.

    Science.gov (United States)

    He, Xinlong; Zou, Yunyun; Cho, Youngjae; Ahn, Juhee

    2012-06-01

    This study was designed to evaluate the effects of bile acid deconjugation by probiotic strains on the antibiotic susceptibility of antibiotic-sensitive and multiple antibiotic-resistant Salmonella Typhimurium and Staphylococcus aureus. Eight probiotic strains, Bifidobacterium longum B6, Lactobacillus acidophilus ADH, Lactobacillus brevis KACC 10553, Lactobacillus casei KACC 12413, Lactobacillus paracasei ATCC 25598, Lactobacillus rhamnosus GG, Leuconostoc mesenteroides KACC 12312, and Pediococcus acidilactici KACC 12307, were used to examine bile acid tolerance. The ability to deconjugate bile acids was evaluated using both thin-layer chromatography and high-performance liquid chromatography. The antibiotic susceptibility testing was carried out to determine the synergistic inhibitory activity of deconjugated bile acids. L. acidophilus, L. brevis, and P. acidilactici showed the most tolerance to the conjugated bile acids. P. acidilactici deconjugated glycocholic acid and glycodeoxycholate from 3.18 and 3.09 mM to the detection limits, respectively. The antibiotic susceptibility of selected foodborne pathogens was increased by increasing the concentration of deconjugated bile acids. The study results are useful for understanding the relationship between bile acid deconjugation by probiotic strains and antibiotic susceptibility in the presence of deconjugated bile acids, and they may be useful for designing new probiotic-antibiotic combination therapy based on bile acid deconjugation.

  6. N-Heterocyclic Carbene-Catalysed Diastereoselective Vinylogous Michael Addition Reaction of gamma-Substituted deconjugated Butenolides

    KAUST Repository

    Guo, Hao; Xing, Fen; Du, Guang-Fen; Huang, Kuo-Wei; Dai, Bin; He, Lin

    2015-01-01

    An efficient N-heterocyclic carbene (NHC)-catalysed vinylogous Michael addition of deconjugated butenolides was developed. In the presence of 5 mol% of the NHC catalyst, both γ-alkyl and aryl-substituted deconjugated butenolides undergo vinylogous Michael addition with various α, β-unsaturated ketones, esters, or nitriles to afford γ,γ-disubstituted butenolides containing adjacent quaternary and tertiary carbon centers in good to excellent yields with excellent diastereoselectivities. In this process, the free carbene is assumed to act as a strong Brønsted base to promote the conjugate addition.

  7. N-Heterocyclic Carbene-Catalysed Diastereoselective Vinylogous Michael Addition Reaction of gamma-Substituted deconjugated Butenolides

    KAUST Repository

    Guo, Hao

    2015-11-16

    An efficient N-heterocyclic carbene (NHC)-catalysed vinylogous Michael addition of deconjugated butenolides was developed. In the presence of 5 mol% of the NHC catalyst, both γ-alkyl and aryl-substituted deconjugated butenolides undergo vinylogous Michael addition with various α, β-unsaturated ketones, esters, or nitriles to afford γ,γ-disubstituted butenolides containing adjacent quaternary and tertiary carbon centers in good to excellent yields with excellent diastereoselectivities. In this process, the free carbene is assumed to act as a strong Brønsted base to promote the conjugate addition.

  8. Blood androgen levels in male baboons throughout the year

    International Nuclear Information System (INIS)

    Taranov, A.G.; Goncharov, N.P.

    1986-01-01

    This paper describes a study of possible dependence of the androgen level in male baboons on the time of year. Plasma was obtained by centrifugation of the blood at 3000 rpm and the following androgens were determined by radioimmunoassay, using chromatographic separation of the steroids on columns with celite: testosterone, 5s-dihydrotestosterone, and dehydroepiandrosterone. Plasma steriod concentrations were calculated and the results were subjected to statistical analysis by Students test. Seasonal change in the concentration of steroids in the animals' blood plasma were discovered. The results of androgen assay throughout the year and determination of their mean annual concentrations are shown

  9. Steroid metabolism by monkey and human spermatozoa

    International Nuclear Information System (INIS)

    Rajalakshmi, M.; Sehgal, A.; Pruthi, J.S.; Anand-Kumar, T.C.

    1983-01-01

    Freshly ejaculated spermatozoa from monkey and human were washed and incubated with tritium labelled androgens or estradiol to study the pattern of spermatozoa steroid metabolism. When equal concentrations of steroid substrates were used for incubation, monkey and human spermatozoa showed very similar pattern of steroid conversion. Spermatozoa from both species converted testosterone mainly to androstenedione, but reverse conversion of androstenedione to testosterone was negligible. Estradiol-17 beta was converted mainly to estrone. The close similarity between the spermatozoa of monkey and men in their steroid metabolic pattern indicates that the rhesus monkey could be an useful animal model to study the effect of drugs on the metabolic pattern of human spermatozoa

  10. Chemical de-conjugation for investigating the stability of small molecule drugs in antibody-drug conjugates.

    Science.gov (United States)

    Chen, Tao; Su, Dian; Gruenhagen, Jason; Gu, Christine; Li, Yi; Yehl, Peter; Chetwyn, Nik P; Medley, Colin D

    2016-01-05

    Antibody-drug conjugates (ADCs) offer new therapeutic options for advanced cancer patients through precision killing with fewer side effects. The stability and efficacy of ADCs are closely related, emphasizing the urgency and importance of gaining a comprehensive understanding of ADC stability. In this work, a chemical de-conjugation approach was developed to investigate the in-situ stability of the small molecule drug while it is conjugated to the antibody. This method involves chemical-mediated release of the small molecule drug from the ADC and subsequent characterization of the released small molecule drug by HPLC. The feasibility of this technique was demonstrated utilizing a model ADC containing a disulfide linker that is sensitive to the reducing environment within cancer cells. Five reducing agents were screened for use in de-conjugation; tris(2-carboxyethyl) phosphine (TCEP) was selected for further optimization due to its high efficiency and clean impurity profile. The optimized de-conjugation assay was shown to have excellent specificity and precision. More importantly, it was shown to be stability indicating, enabling the identification and quantification of the small molecule drug and its degradation products under different formulation pHs and storage temperatures. In summary, the chemical de-conjugation strategy demonstrated here offers a powerful tool to assess the in-situ stability of small molecule drugs on ADCs and the resulting information will shed light on ADC formulation/process development and storage condition selection. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Status of sex steroid hormone receptors in large bowel cancer

    NARCIS (Netherlands)

    Meggouh, F.; Lointier, P.; Pezet, D.; Saez, S.

    1991-01-01

    To determine the potential role of sex steroid hormones in the development of colorectal tumors in humans, specific androgen (AR), estrogen (ER), and progesterone (PGR) receptors were investigated in normal mucosa (NM) and in tumor (T) paired biopsy specimens from 94 patients. Androgen receptors

  12. Leverpatologi associeret med anaboliske-androgene steroider

    DEFF Research Database (Denmark)

    Søe, Katrine; Søe, Martin Jensen; Gluud, C N

    1994-01-01

    that AAS can cause development of hepatocellular carcinomas when used in usual therapeutical doses. Tumours reported as hepatocellular carcinomas caused by AAS seem to be hyperplastic lesions of a benign nature that are able to regress on withdrawal of the putative agent. The effect of untraditional...

  13. Steroid metabolism in the mouse placenta

    International Nuclear Information System (INIS)

    Okker-Reitsma, G.H.

    1976-01-01

    The purpose of the study described in this thesis was to investigate the capacity for steroid synthesis of the mouse placenta - especially the production of progesterone, androgens and estrogens - and to determine, if possible, the relation of steroid synthesis to special cell types. In an introductory chapter the androgen production in the mouse placenta is surveyed by means of a histochemical and bioindicator study of different stages of development of the placenta. The metabolism of [ 3 H]-dehydroepiandrosterone and [ 3 H]-progesterone by mouse placental tissue in vitro is studied. The metabolism of [ 3 H]-progesterone by the mouse fetal adrenal in vitro is also studied

  14. An enzymatic deconjugation method for the analysis of small molecule active drugs on antibody-drug conjugates.

    Science.gov (United States)

    Li, Yi; Gu, Christine; Gruenhagen, Jason; Yehl, Peter; Chetwyn, Nik P; Medley, Colin D

    2016-01-01

    Antibody-drug conjugates (ADCs) are complex therapeutic agents that use the specific targeting properties of antibodies and the highly potent cytotoxicity of small molecule drugs to selectively eliminate tumor cells while limiting the toxicity to normal healthy tissues. Two critical quality attributes of ADCs are the purity and stability of the active small molecule drug linked to the ADC, but these are difficult to assess once the drug is conjugated to the antibody. In this study, we report a enzyme deconjugation approach to cleave small molecule drugs from ADCs, which allows the drugs to be subsequently characterized by reversed-phase high performance liquid chromatography. The model ADC we used in this study utilizes a valine-citrulline linker that is designed to be sensitive to endoproteases after internalization by tumor cells. We screened several proteases to determine the most effective enzyme. Among the 3 cysteine proteases evaluated, papain had the best efficiency in cleaving the small molecule drug from the model ADC. The deconjugation conditions were further optimized to achieve complete cleavage of the small molecule drug. This papain deconjugation approach demonstrated excellent specificity and precision. The purity and stability of the active drug on an ADC drug product was evaluated and the major degradation products of the active drug were identified. The papain deconjugation method was also applied to several other ADCs, with the results suggesting it could be applied generally to ADCs containing a valine-citrulline linker. Our results indicate that the papain deconjugation method is a powerful tool for characterizing the active small molecule drug conjugated to an ADC, and may be useful in ensuring the product quality, efficacy and the safety of ADCs.

  15. Steroidal Saponins

    Science.gov (United States)

    Sahu, N. P.; Banerjee, S.; Mondal, N. B.; Mandal, D.

    The medicinal activities of plants are generally due to the secondary metabolites (1) which often occur as glycosides of steroids, terpenoids, phenols etc. Saponins are a group of naturally occurring plant glycosides, characterized by their strong foam-forming properties in aqueous solution. The cardiac glycosides also possess this, property but are classified separately because of their specific biological activity. Unlike the cardiac glycosides, saponins generally do not affect the heart. These are classified as steroid or triterpenoid saponins depending on the nature of the aglycone. Steroidal glycosides are naturally occurring sugar conjugates of C27 steroidal compounds. The aglycone of a steroid saponin is usually a spirostanol or a furostanol. The glycone parts of these compounds are mostly oligosaccharides, arranged either in a linear or branched fashion, attached to hydroxyl groups through an acetal linkage (2, 3). Another class of saponins, the basic steroid saponins, contain nitrogen analogues of steroid sapogenins as aglycones.

  16. Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery.

    Science.gov (United States)

    Segal, Scott; Narayanan, Ramesh; Dalton, James T

    2006-04-01

    Selective androgen receptor modulators (SARMS) bind to the androgen receptor and demonstrate anabolic activity in a variety of tissues; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents are able to induce bone and muscle growth, as well as shrinking the prostate. The potential of SARMS is to maximise the positive attributes of steroidal androgens as well as minimising negative effects, thus providing therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. This review summarises androgen physiology, the current status of the R&D of SARMS and potential therapeutic indications for this emerging class of drugs.

  17. Steroid osteopathy

    Energy Technology Data Exchange (ETDEWEB)

    Conway, J.J.; Weiss, S.C.

    1984-01-01

    Patients receiving steroids or having disease processes which increase natural steroid production often demonstrate ''the classic x-ray changes'' of avascular necrosis of bone. Bone scintigraphy in these patients most frequently demonstrates an increased radionuclide localization. The literature suggests that the increased activity is related to healing of the avascular process. In a recent study of Legg-Calve-Perthes Disease (LCPD), 37 of the children had multiple studies and increased activity within the epiphysis during revascularization was extremely rare. Not only are the scintigraphic findings in steroid osteopathy dissimilar to that in healing LCPD, but the time interval for healing is much to short for that of a vascular necrosis and no patients demonstrated an avascular phase on bone scintigraphy. Of 15 children with renal transplants on steroid therapy, 9 demonstrated x-ray and clinical findings of osteopathy. In 8 of 9 instances, bone scintigraphy showed increased localization of radionuclide in the affected bone. Improvement or a return to normal occurred in those patients in whom steroids were discontinued. The following is a proposed mechanism for steroid osteopathy. Steroids affect the osteoblastic and osteoclastic activity of bone and weaken its internal structure. Ordinary stress produces microtrabecular fractures. Fractures characteristically stimulate reactive hyperemia and increase bone metabolism. The result is increased bone radiopharmaceutical localization. The importance of recognizing this concept is that steroid osteopathy is preventable by reducing the administered steroid dose. As opposed to avascular necrosis, bone changes are reversible.

  18. Steroid osteopathy

    International Nuclear Information System (INIS)

    Conway, J.J.; Weiss, S.C.

    1984-01-01

    Patients receiving steroids or having disease processes which increase natural steroid production often demonstrate ''the classic x-ray changes'' of avascular necrosis of bone. Bone scintigraphy in these patients most frequently demonstrates an increased radionuclide localization. The literature suggests that the increased activity is related to healing of the avascular process. In a recent study of Legg-Calve-Perthes Disease (LCPD), 37 of the children had multiple studies and increased activity within the epiphysis during revascularization was extremely rare. Not only are the scintigraphic findings in steroid osteopathy dissimilar to that in healing LCPD, but the time interval for healing is much to short for that of a vascular necrosis and no patients demonstrated an avascular phase on bone scintigraphy. Of 15 children with renal transplants on steroid therapy, 9 demonstrated x-ray and clinical findings of osteopathy. In 8 of 9 instances, bone scintigraphy showed increased localization of radionuclide in the affected bone. Improvement or a return to normal occurred in those patients in whom steroids were discontinued. The following is a proposed mechanism for steroid osteopathy. Steroids affect the osteoblastic and osteoclastic activity of bone and weaken its internal structure. Ordinary stress produces microtrabecular fractures. Fractures characteristically stimulate reactive hyperemia and increase bone metabolism. The result is increased bone radiopharmaceutical localization. The importance of recognizing this concept is that steroid osteopathy is preventable by reducing the administered steroid dose. As opposed to avascular necrosis, bone changes are reversible

  19. Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

    Science.gov (United States)

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2016-11-01

    Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Androgenic signaling systems and their role in behavioral evolution.

    Science.gov (United States)

    Fuxjager, Matthew J; Schuppe, Eric R

    2018-06-05

    Sex steroids mediate the organization and activation of masculine reproductive phenotypes in diverse vertebrate taxa. However, the effects of sex steroid action in this context vary tremendously, in that steroid action influences reproductive physiology and behavior in markedly different ways (even among closely related species). This leads to the idea that the mechanisms underlying sex steroid action similarly differ across vertebrates in a manner that supports diversification of important sexual traits. Here, we highlight the Evolutionary Potential Hypothesis as a framework for understanding how androgen-dependent reproductive behavior evolves. This idea posits that the cellular mechanisms underlying androgenic action can independently evolve within a given target tissue to adjust the hormone's functional effects. The result is a seemingly endless number of permutations in androgenic signaling pathways that can be mapped onto the incredible diversity of reproductive phenotypes. One reason this hypothesis is important is because it shifts current thinking about the evolution of steroid-dependent traits away from an emphasis on circulating steroid levels and toward a focus on molecular mechanisms of hormone action. To this end, we also provide new empirical data suggesting that certain cellular modulators of androgen action-namely, the co-factors that dynamically adjust transcritpional effects of steroid action either up or down-are also substrates on which evolution can act. We then close the review with a detailed look at a case study in the golden-collared manakin (Manacus vitellinus). Work in this tropical bird shows how androgenic signaling systems are modified in specific parts of the skeletal muscle system to enhance motor performance necessary to produce acrobatic courtship displays. Altogether, this paper seeks to develop a platform to better understand how steroid action influences the evolution of complex animal behavior. Copyright © 2018 Elsevier Ltd

  1. Oral Steroids (Steroid Pills and Syrups)

    Science.gov (United States)

    ... steroid bursts can cause a number of side effects. Steroid side effects usually occur after long-term use ... how the dosage of steroids is determined; side effects of inhaled steroids, and some recommendations to decrease or prevent side ...

  2. Androgens and estrogens in skeletal sexual dimorphism

    Directory of Open Access Journals (Sweden)

    Michaël Laurent

    2014-04-01

    Full Text Available Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T to estradiol (E2 by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refi ned our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen defi ciency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the fi eld of sex steroid actions in male bone homeostasis.

  3. Androgens and estrogens in skeletal sexual dimorphism

    Science.gov (United States)

    Laurent, Michaël; Antonio, Leen; Sinnesael, Mieke; Dubois, Vanessa; Gielen, Evelien; Classens, Frank; Vanderschueren, Dirk

    2014-01-01

    Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. PMID:24385015

  4. Female adipocyte androgen synthesis and the effects of insulin

    Directory of Open Access Journals (Sweden)

    David Cadagan

    2014-01-01

    Full Text Available The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione in vitro and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.

  5. Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation.

    Directory of Open Access Journals (Sweden)

    Pilar Galindo

    Full Text Available BACKGROUND: Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3'-sulfate, Q3'S in spontaneously hypertensive rats (SHR. Q3GA and I3GA (1 mg/kg i.v., but not Q3'S, progressively reduced mean blood pressure (MBP, measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml. In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg induced a progressive decrease in MBP, which was also suppressed by SAL. CONCLUSIONS: Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect.

  6. Androgen insensitivity syndrome: gonadal androgen receptor activity

    International Nuclear Information System (INIS)

    Coulam, C.B.; Graham, M.L.; Spelsberg, T.C.

    1984-01-01

    To determine whether abnormalities of the androgen receptor previously observed in skin fibroblasts from patients with androgen insensitivity syndrome also occur in the gonads of affected individuals, androgen receptor activity in the gonads of a patient with testicular feminization syndrome was investigated. Using conditions for optimal recovery of androgen receptor from human testes established by previous studies, we detected the presence of a high-affinity (dissociation constant . 3.2 X 10(-10) mol/L), low-capacity (4.2 X 10(-12) mol/mg DNA), androgen-binding protein when tritium-labeled R1881 was incubated at 4 degrees C with nuclear extracts from the gonads of control patients or from a patient with testicular feminization syndrome but not when incubated at 37 degrees C. Thus this patient has an androgen receptor with a temperature lability similar to that of receptors from normal persons

  7. Sex Steroid Actions in Male Bone

    Science.gov (United States)

    Laurent, Michaël R.; Claessens, Frank; Gielen, Evelien; Lagerquist, Marie K.; Vandenput, Liesbeth; Börjesson, Anna E.; Ohlsson, Claes

    2014-01-01

    Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority. PMID:25202834

  8. Seasonal changes in steroid metabolism in the male reproductive organ-system of the African catfish, Clarias gariepinus

    NARCIS (Netherlands)

    Resink, J.W.; Schoonen, W.G.E.J.; Hurk, R. van den; Viveen, W.J.A.R.; Lambert, J.G.D.

    1987-01-01

    Steroid and steroid glucuronide synthesis in feral male African catfish was investigated in vitro by incubating testes with [3H]-pregnenolone and seminal vesicles with [3H]-androstenedione. In testes, the capacity to form progestins, androgens, especially 11-oxygenated ones, and steroid glucuronides

  9. Atmospheric Pressure Photoionization Tandem Mass Spectrometry of Androgens in Prostate Cancer

    Science.gov (United States)

    Lih, Fred Bjørn; Titus, Mark A.; Mohler, James L.; Tomer, Kenneth B.

    2010-01-01

    Androgen deprivation therapy is the most common treatment option for advanced prostate cancer. Almost all prostate cancers recur during androgen deprivation therapy, and new evidence suggests that androgen receptor activation persists despite castrate levels of circulating androgens. Quantitation of tissue levels of androgens is critical to understanding the mechanism of recurrence of prostate cancer during androgen deprivation therapy. A liquid chromatography atmospheric pressure photoionization tandem mass spectrometric method was developed for quantitation of tissue levels of androgens. Quantitation of the saturated keto-steroids dihydrotestosterone and 5-α-androstanedione required detection of a novel parent ion, [M + 15]+. The nature of this parent ion was explored and the method applied to prostate tissue and cell culture with comparison to results achieved using electrospray ionization. PMID:20560527

  10. Profiling of androgen response in rainbow trout pubertal testis: relevance to male gonad development and spermatogenesis.

    Directory of Open Access Journals (Sweden)

    Antoine D Rolland

    Full Text Available The capacity of testicular somatic cells to promote and sustain germ cell differentiation is largely regulated by sexual steroids and notably androgens. In fish species the importance of androgens is emphasized by their ability to induce sex reversal of the developing fries and to trigger spermatogenesis. Here we studied the influence of androgens on testicular gene expression in trout testis using microarrays. Following treatment of immature males with physiological doses of testosterone or 11-ketotestosterone, 418 genes that exhibit changes in expression were identified. Interestingly, the activity of testosterone appeared stronger than that of 11-ketotestosterone. Expression profiles of responsive genes throughout testis development and in isolated germ cells confirmed androgens to mainly affect gene expression in somatic cells. Furthermore, specific clusters of genes that exhibit regulation coincidently with changes in the natural circulating levels of androgens during the reproductive cycle were highlighted, reinforcing the physiological significance of these data. Among somatic genes, a phylogenetic footprinting study identified putative androgen response elements within the proximal promoter regions of 42 potential direct androgen target genes. Finally, androgens were also found to alter the germ line towards meiotic expression profiles, supporting the hypothesis of a role for the somatic responsive genes in driving germ cell fate. This study significantly increases our understanding of molecular pathways regulated by androgens in vertebrates. The highly cyclic testicular development in trout together with functions associated with regulated genes reveal potential mechanisms for androgen actions in tubule formation, steroid production, germ cell development and sperm secretion.

  11. 5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer.

    Science.gov (United States)

    Uemura, Motohide; Honma, Seijiro; Chung, Suyoun; Takata, Ryo; Furihata, Mutsuo; Nishimura, Kazuo; Nonomura, Norio; Nasu, Yasutomo; Miki, Tsuneharu; Shuin, Taro; Fujioka, Tomoaki; Okuyama, Akihiko; Nakamura, Yusuke; Nakagawa, Hidewaki

    2010-08-01

    Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

  12. The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells

    International Nuclear Information System (INIS)

    Chuu, Chih-pin; Chen, Rou-Yu; Hiipakka, Richard A.; Kokontis, John M.; Warner, Karen V.; Xiang, Jialing; Liao, Shutsung

    2007-01-01

    T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells

  13. Detection of seventy-two anabolic and androgenic steroids and/or their esters in horse hair using ultra-high performance liquid chromatography-high resolution mass spectrometry in multiplexed targeted MS2 mode and gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Choi, Timmy L S; Kwok, Karen Y; Kwok, Wai Him; Tsoi, Yeuki Y K; Wong, Jenny K Y; Wan, Terence S M

    2018-06-20

    Anabolic and androgenic steroids (AAS) are banned substances in both human and equine sports. They are often administered intramuscularly to horses in esterified forms for the purpose of extending their time of action. The authors' laboratory has previously reported an UHPLC/HRMS method using quadrupole-Orbitrap mass spectrometer in full scan and parallel reaction monitoring (PRM) mode for the detection of 48 AAS and/or their esters in horse hair. However, two injections were required due to the long duty cycle time. In this paper, an UHPLC/HRMS method using multiplexed targeted MS 2 mode was developed and validated to improve the coverage to 65 AAS and/or their esters in a single injection. In addition, a GC/MS/MS method in selected reaction monitoring (SRM) mode was developed to screen for another seven AAS and/or their esters not adequately covered by the UHPLC/HRMS method using the same sample extract after derivatisation with pentafluoropropionic anhydride. The UHPLC/HRMS and GC/MS/MS methods in combination allowed the detection of 72 AAS and/or their esters with estimated limits of detection down to sub to low ppb levels with good interday precision. Method applicability was demonstrated by the detection of boldione and 4-androstenedione in two out-of-competition hair samples and testosterone propionate in a referee hair sample. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. The role of steroids in follicular growth

    Directory of Open Access Journals (Sweden)

    Drummond Ann E

    2006-04-01

    Full Text Available Abstract The steroidogenic pathway within the ovary gives rise to progestins, androgens and oestrogens, all of which act via specific nuclear receptors to regulate reproductive function and maintain fertility. The role of progestins in follicular growth and development is limited, its action confined largely to ovulation, although direct effects on granulosa cell function have been reported. Consistent with these findings, progesterone receptor knockout mice are infertile because they cannot ovulate. Androgens have been shown to promote early follicular growth, but also to impede follicular development by stimulating atresia and apoptosis. The inability of androgens to transduce a signal in mice lacking androgen receptors culminates in reduced fertility. Oestrogens are known to exert effects on granulosa cell growth and differentiation in association with gonadotrophins. Studies with oestrogen receptor knockouts and oestrogen depleted mice have shown us that oestrogen is essential for folliculogenesis beyond the antral stage and is necessary to maintain the female phenotype of ovarian somatic cells. In summary, the action of steroids within the ovary is based on the developmental status of the follicle. In the absence of any single sex steroid, ovarian function and subsequently fertility, are compromised.

  15. Anabolic Steroids: A Threat to Body and Mind. National Institute on Drug Abuse Research Report Series.

    Science.gov (United States)

    National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

    This report, based on findings of recent studies on the use of anabolic steroids in the United States, was written to educate the public about these drugs and the dangers of misusing them. It notes that the nonmedical use of anabolic/androgenic steroids among adolescents and young adults is of growing concern, with possibly as many as half a…

  16. Androgens and Hypertension in Men and Women: a Unifying View.

    Science.gov (United States)

    Moretti, Costanzo; Lanzolla, Giulia; Moretti, Marta; Gnessi, Lucio; Carmina, Enrico

    2017-05-01

    This review was designed to revaluate the androgen role on the mechanisms of hypertension and cardiovascular risks in both men and women. Sex steroids are involved in the regulation of blood pressure, but pathophysiological mechanism is not well understood. Androgens have an important effect on metabolism, adipose and endothelial cell function, and cardiovascular risk in both men and women. A focal point in this contest is represented by the possible gender-specific regulation of different tissues and in particular of the adipose cell. Available data confirm that androgen deficiency is linked to increased prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction seems to be the main involved mechanism. Androgen replacement reduces inflammation state in man, protecting by metabolic syndrome progression. In women, androgen excess has been considered as promoting factor of cardiovascular risk. However, recent data suggest that excessive androgen production has little effect per se in inducing hypertension in young women of reproductive age. Also in postmenopausal women, data on relative androgen excess and hypertension are missing, while adrenal androgen deficiency has been associated to increased mortality. Molecular mechanisms linking androgen dysregulation to hypertension are almost Unknown, but they seem to be related to increased visceral fat, promoting a chronic inflammatory state through different mechanisms. One of these may involve the recruitment and over-activation of NF-kB, a ubiquitous transcription factor also expressed in adipose cells, where it may cause the production of cytokines and other immune factors. The NF-kB signalling pathway may also influence brown adipogenesis leading to the preferential enlargement of visceral adipocytes. Chronic inflammation and adipocyte dysfunction may alter endothelial function leading to hypertension. Both in men and in women, particularly in the post-menopausal period, hypoandrogenism seems to be

  17. Adverse cardiovascular effects of anabolic steroids : pathophysiology imaging

    NARCIS (Netherlands)

    Golestani, Reza; Slart, Riemer H. J. A.; Dullaart, Robin P. F.; Glaudemans, Andor W. J. M.; Zeebregts, Clark J.; Boersma, Hendrikus H.; Tio, Rene A.; Dierckx, Rudi A. J. O.

    Eur J Clin Invest 2012; 42 (7): 795803 Abstract Background Anabolic-androgenic steroids (AAS) are widely abused for enhancing muscle mass, strength, growth and improving athletic performance. Materials and methods In recent years, many observational and interventional studies have shown important

  18. Uso de esteróides anabólicos androgênicos por praticantes de musculação de grandes academias da cidade de São Paulo Use of anabolic-androgenic steroids among body builders in major gym centers in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Luciana Silvia Maria Franco Silva

    2003-09-01

    Full Text Available O objetivo desta pesquisa foi estimar o consumo e traçar o perfil dos usuários de esteróides anabólicos androgênicos (EAA entre praticantes de musculação em três grandes academias de ginástica na cidade de São Paulo. Foi utilizado um questionário estruturado para ser respondido voluntária e anonimamente, com garantia explícita de confidencialidade para os mesmos. Os questionários ficaram disponíveis em três academias por uma semana, após ter sido feita ampla divulgação dos objetivos e importância do projeto. Responderam o questionário 209 praticantes de musculação (cerca de 3% do total. A incidência de uso de EAA foi de 19%, sendo que, destes, 8% declararam que fazem uso atualmente e 11%, que já haviam feito uso anteriormente; considerando apenas o sexo masculino, a incidência do uso foi de 24%. Os compostos mais utilizados foram estanozolol e decanoato de nandrolona. O perfil dos usuários pôde ser delineado: idade média de 27 anos (de 25 a 29 anos, predominantemente homens, motivação pela melhora na estética corporal e treinamento muscular intenso. Os EAA foram adquiridos, em sua maioria, em farmácias, sem receita médica e foram feitos uso de suplemento alimentar e outros fármacos em associação. Acreditam que os efeitos tóxicos/adversos podem ser controlados e/ou evitados com o uso de outros medicamentos e/ou acompanhamento médico. O presente trabalho mostra a necessidade de investigações mais abrangentes e aprofundadas, bem como a adoção de ações preventivas e educativas junto à população exposta aos EAA.To estimate the use of anabolic-androgenic steroids (AAS among body builders of three - professionally equipped private gym in São Paulo, Brazil, body builders answered voluntary and anonimously a structured multiple itens questionnaire which was available for a week in these gym centers. The participants were informed in advance of the aim of the study. Of the 209 body builders attending (3% of

  19. Androgens and the male reproductive tract: an overview of classical roles and current perspectives.

    Science.gov (United States)

    Patrão, Marilia T C C; Silva, Erick J R; Avellar, Maria Christina W

    2009-11-01

    Androgens are steroid hormones that play key roles in the development and maintenance of male phenotype and reproductive function. These hormones also affect the function of several non-reproductive organs, such as bone and skeletal muscle. Endogenous androgens exert most of their effects by genomic mechanisms, which involve hormone binding to the androgen receptor (AR), a ligand-activated transcription factor, resulting in the modulation of gene expression. AR-induced non-genomic mechanisms have also been reported. A large number of steroidal and non-steroidal AR-ligands have been developed for therapeutic use, including the treatment of male hypogonadism (AR agonists) and prostate diseases (AR antagonists), among other pathological conditions. Here, the AR gene and protein structure, mechanism of action and AR gene homologous regulation were reviewed. The AR expression pattern, its in vivo regulation and physiological relevance in the developing and adult testis and epididymis, which are sites of sperm production and maturation, respectively, were also presented.

  20. Molecular basis of androgen insensitivity

    NARCIS (Netherlands)

    Brinkmann, A.; Jenster, G.; Ris-Stalpers, C.; van der Korput, H.; Brüggenwirth, H.; Boehmer, A.; Trapman, J.

    1996-01-01

    Male sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. In the X-linked androgen insensitivity syndrome, defects in the

  1. Estrogens and Androgens in Skeletal Physiology and Pathophysiology.

    Science.gov (United States)

    Almeida, Maria; Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C

    2017-01-01

    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. Copyright © 2017 the American Physiological Society.

  2. Gonadal steroids and bone metabolism in men.

    Science.gov (United States)

    Leder, Benjamin

    2007-06-01

    Over the past decade, our increasing awareness of the clinical importance of osteoporosis in men has stimulated intense interest in trying to better understand male skeletal physiology and pathophysiology. The present review focuses on a major focus of research in this area, namely the attempt to define the influence and therapeutic potential of gonadal steroids in male bone metabolism. Building on previous work defining the relative roles of androgens and estrogens in the developing male skeleton and in maintaining normal bone turnover, recent studies have begun to define these issues from epidemiologic, physiologic and therapeutic perspectives. With access to data from large prospectively defined populations of men, investigators are confirming and challenging existing hypotheses and forwarding new concepts. Clinical trials have expanded beyond standard androgen replacement studies to explore more complex hormonal interventions. Physiologic investigation has continued to probe the mechanisms underlying the differential and independent roles of androgens and estrogens in male bone metabolism. Recent work has added significantly to our understanding of the role of gonadal steroids in male skeletal physiology. Nonetheless, further research is necessary to build on these initial human studies and to capitalize on rapidly emerging advances in our understanding of the basic biology of bone metabolism.

  3. QSAR models for anti-androgenic effect - a preliminary study

    DEFF Research Database (Denmark)

    Jensen, Gunde Egeskov; Nikolov, Nikolai Georgiev; Wedebye, Eva Bay

    2011-01-01

    Three modelling systems (MultiCase (R), LeadScope (R) and MDL (R) QSAR) were used for construction of androgenic receptor antagonist models. There were 923-942 chemicals in the training sets. The models were cross-validated (leave-groups-out) with concordances of 77-81%, specificity of 78...... of the model for a particular application, balance of training sets, domain definition, and cut-offs for prediction interpretation should also be taken into account. Different descriptors in the modelling systems are illustrated with hydroxyflutamide and dexamethasone as examples (a non-steroid and a steroid...

  4. The alteration of the urinary steroid profile under the stress

    Directory of Open Access Journals (Sweden)

    A Gronowska

    2010-03-01

    Full Text Available In the second part of twentieth century anabolic-androgenic steroids were introduced into doping practice and received continuously increasing significance. In order to prove the usage of doping substances, the determination of steroid profile in the urine came into practice. Several factors may be responsible for alterations in the normal steroid profile for example age, sex and diet. The aim of this study was to find out, whether the psychological stress may cause modifications in the steroid profile and T/Et ratio. The effect of physical activity was also considered. The steroid profile was determined in the group of 34 students being in non-stress conditions and under stress immediately before an important university exam. The intensity of stress was rated by self-reported questionnaire. The GC/MS method was applied to determine the steroid profile in the urine samples. The results of the experiment have shown that psychological stress may cause significant changes in the steroid profile, especially in females. Physical activity, independently of stress significantly modified the steroid profile. In summary, observed changes in steroid profile suggest, that major fluctuations of T/Et and A/E ratios under the influence of stressogenic factors and physical activity are unlikely.

  5. Deconjugated bile salts produced by extracellular bile-salt hydrolase-like activities from the probiotic Lactobacillus johnsonii La1 inhibit Giardia duodenalis in vitro growth

    Directory of Open Access Journals (Sweden)

    Marie-Agnès Travers

    2016-09-01

    Full Text Available Giardiasis, currently considered a neglected disease, is caused by the intestinal protozoan parasite Giardia duodenalis and is widely spread in human as well as domestic and wild animals. The lack of appropriate medications and the spread of resistant parasite strains urgently call for the development of novel therapeutic strategies. Host microbiota or certain probiotic strains have the capacity to provide some protection against giardiasis. By combining biological and biochemical approaches, we have been able to decipher a molecular mechanism used by the probiotic strain Lactobacillus johnsonii La1 to prevent Giardia growth in vitro. We provide evidence that the supernatant of this strain contains active principle(s not directly toxic to Giardia but able to convert non-toxic components of bile into components highly toxic to Giardia. By using bile acid profiling, these components were identified as deconjugated bile-salts. A bacterial bile-salt-hydrolase of commercial origin was able to mimic the properties of the supernatant. Mass spectrometric analysis of the bacterial supernatant identified two of the three bile-salt-hydrolases encoded in the genome of this probiotic strain. These observations document a possible mechanism by which L. johnsonii La1, by secreting or releasing BSH-like activity(ies in the vicinity of replicating Giardia in an environment where bile is present and abundant, can fight this parasite. This discovery has both fundamental and applied outcomes to fight giardiasis, based on local delivery of deconjugated bile salts, enzyme deconjugation of bile components, or natural or recombinant probiotic strains that secrete or release such deconjugating activities in a compartment where both bile salts and Giardia are present.

  6. Androgen receptor and histone lysine demethylases in ovine placenta.

    Directory of Open Access Journals (Sweden)

    Ellane R Cleys

    Full Text Available Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR. Prenatal androgenization decreased global DNA methylation in gestational day 90 placentomes, and increased placental expression of AR as well as genes involved in epigenetic regulation, angiogenesis, and growth. As AR complexes with histone lysine demethylases (KDMs to regulate AR target genes in human cancers, we also investigated if the same mechanism is present in the ovine placenta. AR co-immunoprecipitated with KDM1A and KDM4D in sheep placentomes, and AR-KDM1A complexes were recruited to a half-site for androgen response element (ARE in the promoter region of VEGFA. Androgenized ewes also had increased cotyledonary VEGFA. Finally, in human first trimester placental samples KDM1A and KDM4D immunolocalized to the syncytiotrophoblast, with nuclear KDM1A and KDM4D immunostaining also present in the villous stroma. In conclusion, placental androgen signaling, possibly through AR-KDM complex recruitment to AREs, regulates placental VEGFA expression. AR and KDMs are also present in first trimester human placenta. Androgens appear to be an important regulator of trophoblast differentiation and placental development, and aberrant androgen signaling may contribute to the development of placental disorders.

  7. Prevalent flucocorticoid and androgen activity in US water sources

    Science.gov (United States)

    Stavreva, Diana A.; George, Anuja A.; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C.; Schiltz, R. Louis; Blazer, Vicki; Iwanowiczl, Luke R.; Hager, Gordon L.

    2012-01-01

    Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

  8. Prevalent glucocorticoid and androgen activity in US water sources.

    Science.gov (United States)

    Stavreva, Diana A; George, Anuja A; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C; Schiltz, R Louis; Blazer, Vicki S; Iwanowicz, Luke R; Hager, Gordon L

    2012-01-01

    Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

  9. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function

    NARCIS (Netherlands)

    Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

    Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CBI

  10. Ovarian overproduction of androgens

    Science.gov (United States)

    ... the body's testosterone. Tumors of the ovaries and polycystic ovary syndrome (PCOS) can both cause too much androgen production. ... come back after they have been removed. In polycystic ovary syndrome, the following measures can reduce symptoms caused by ...

  11. Negative regulation of parathyroid hormone-related protein expression by steroid hormones

    International Nuclear Information System (INIS)

    Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

    2011-01-01

    Highlights: → Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. → Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. → Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

  12. Steroid radioimmunoassays

    International Nuclear Information System (INIS)

    Shinde, Y.; Hacker, R.R.; Ntunde, B.; Smith, V.G.

    1981-01-01

    An estrogen radioimmunoassay was used to study the problem of blanks in steroid assays. Negligible binding (1.5 percent) in the non-antibody tubes prevailed throughout the study. The assay was validated using accepted procedures. Both water and solvent blanks had estrogen concentrations of 7-9 pg/tube. However, neither water nor solvent blanks showed a dose-related response, indicating that they were 'real' blanks. Exogenous estradiol, when added to water and solvent in quantities less than the estimated blank, was not quantitatively recovered. However, exogenous estradiol added to the water solvent in quantities greater than the blank estimate was quantitatively recovered. The sensitivity of the reference standard curve was 6-10 pg/tube, approximately the same as the blank estimate. These results indicated that the estimates of water and solvent blanks were measures of the assay sensitivity. In such circumstances, it is suggested that blank estimates should not be subtracted from sample values. If the blank estimates are high, attention should be directed towards improving the sensitivity of the assay

  13. Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

    Science.gov (United States)

    Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

    2013-11-01

    Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

  14. Androgens and alopecia.

    Science.gov (United States)

    Kaufman, Keith D

    2002-12-30

    Androgens have profound effects on scalp and body hair in humans. Scalp hair grows constitutively in the absence of androgens, while body hair growth is dependent on the action of androgens. Androgenetic alopecia, referred to as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is due to the progressive miniaturization of scalp hair. Observations in both eunuchs, who have low levels of testicular androgens, and males with genetic 5alpha-reductase (5alphaR) deficiency, who have low levels of dihydrotestosterone (DHT), implicate DHT as a key androgen in the pathogenesis of MPHL in men. The development of finasteride, a type 2-selective 5alphaR inhibitor, further advanced our understanding of the role of DHT in the pathophysiology of scalp alopecia. Controlled clinical trials with finasteride demonstrated improvements in scalp hair growth in treated men associated with reductions in scalp DHT content, and a trend towards reversal of scalp hair miniaturization was evident by histopathologic evaluation of scalp biopsies. In contrast to its beneficial effects in men, finasteride did not improve hair growth in postmenopausal women with FPHL. Histopathological evaluation of scalp biopsies confirmed that finasteride treatment produced no benefit on scalp hair in these women. These findings suggest that MPHL and FPHL are distinct clinical entities, with disparate pathophysiologies. Studies that elucidate the molecular mechanisms by which androgens regulate hair growth would provide greater understanding of these differences. Copyright 2002 Elsevier Science Ireland Ltd.

  15. Steroid hormones level in milk of non-pregnant and pregnant river buffalos at various gestational trimesters

    Directory of Open Access Journals (Sweden)

    Yaser Shahbazi

    2011-09-01

    Full Text Available Background: Milk is a valuable sources of nutrition in the human diet however; there are reports on safety of milk steroid hormones contain. This study designed to determine the level of steroid hormones including estrone (E1, 17β-estradiol (E2, and estriol (E3 in raw and pasteurized milk from non-pregnant and pregnant buffalos.Methods: Steroids was extracted using liquid extraction, enzymatical deconjugation, and C18 solid-phase extraction from collected milk samples. Estrogens were analyzed using high performance liquid chromatography equipped by fluorescence detector.Results: Free E1 (554.1±77.0 ng/L and deconjugated E1 (701.6±44.7 ng/L was found highest level estrogen followed by E2, while E3 level was under the detection limit (10 ng/L. The lowest E1: 554.1±77.0 and E2: 28.1±4.4ng/L estrogens level were determined in raw milk from non-pregnant and highest E1: 1014.7±123.8 and E2: 108.2±9.1 ng/L estrogens were found in milk of animals in the third trimester of gestation. The estrogens concentration in pasteurized milk did not show significant (P>0.05 differences with those in raw milk.Conclusion: As buffalo milk poses more fat than cow's milk, it may contain higher level of steroid hormones. Since consumption of buffalo's milk with higher amount of steroidal hormones could be considered one of the potential risk factors for carcinogenesis.

  16. Androgen regulation of the androgen receptor coregulators

    International Nuclear Information System (INIS)

    Urbanucci, Alfonso; Waltering, Kati K; Suikki, Hanna E; Helenius, Merja A; Visakorpi, Tapio

    2008-01-01

    The critical role of the androgen receptor (AR) in the development of prostate cancer is well recognized. The transcriptional activity of AR is partly regulated by coregulatory proteins. It has been suggested that these coregulators could also be important in the progression of prostate cancer. The aim of this study was to identify coregulators whose expression is regulated by either the androgens and/or by the expression level of AR. We used empty vector and AR cDNA-transfected LNCaP cells (LNCaP-pcDNA3.1, and LNCaP-ARhi, respectively), and grew them for 4 and 24 hours in the presence of dihydrotestosterone (DHT) at various concentrations. The expression of 25 AR coregulators (SRC1, TIF2, PIAS1, PIASx, ARIP4, BRCA1, β-catenin, AIB3, AIB1, CBP, STAT1, NCoR1, AES, cyclin D1, p300, ARA24, LSD1, BAG1L, gelsolin, prohibitin, JMJD2C, JMJD1A, MAK, PAK6 and MAGE11) was then measured by using real-time quantitative RT-PCR (Q-RT-PCR). Five of the coregulators (AIB1, CBP, MAK, BRCA1 and β-catenin) showed more than 2-fold induction and 5 others (cyclin D1, gelsolin, prohibitin, JMJD1A, and JMJD2C) less than 2-fold induction. Overexpression of AR did not affect the expression of the coregulators alone. However, overexpression of AR enhanced the DHT-stimulated expression of MAK, BRCA1, AIB1 and CBP and reduced the level of expression of β-catenin, cyclinD1 and gelsolin. In conclusion, we identified 5 coactivators whose expression was induced by androgens suggesting that they could potentiate AR signaling. Overexpression of AR seems to sensitize cells for low levels of androgens

  17. Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226

    International Nuclear Information System (INIS)

    Wang, Feng; Liu, Xiao-qin; Li, He; Liang, Kai-ni; Miner, Jeffrey N.; Hong, Mei; Kallel, E. Adam; Oeveren, Arjan van; Zhi, Lin; Jiang, Tao

    2006-01-01

    Crystal structure of the ligand-binding domain of androgen receptor in complex with LGD2226. The androgen receptor (AR) is a ligand-inducible steroid hormone receptor that mediates androgen action, determining male sexual phenotypes and promoting spermatogenesis. As the androgens play a dominant role in male sexual development and function, steroidal androgen agonists have been used clinically for some years. However, there is a risk of potential side effects and most steroidal androgens cannot be dosed orally, which limits the use of these substances. 1,2-Dihydro-6-N,N-bis(2,2,2-trifluoroethyl) amino-4-trifluoromethyl-2-quinolinone (LGD2226) is a synthetic nonsteroidal ligand and a novel selective AR modulator. The crystal structure of the complex of LGD2226 with the androgen receptor ligand-binding domain (AR LBD) at 2.1 Å was solved and compared with the structure of the AR LBD–R1881 complex. It is hoped that this will aid in further explaining the selectivity of LGD2226 observed in in vitro and in vivo assays and in developing more selective and effective therapeutic agents

  18. The clinical and molecular spectrum of androgen insensitivity syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Hiort, O.; Sinnecker, G.H.G.; Holterhus, P.M.; Nitsche, E.M.; Kruse, K. [Medical Univ. of Luebeck (Germany)

    1996-05-03

    Androgen insensitivity syndromes (AIS) are due to end-organ resistance to androgenic steroids in males leading to defective virilization of the external genitalia. The phenotype encompasses a wide array of genital ambiguity and may range from completely female to undervirilized but unequivocally male with infertility. This disorder is caused by mutations of the androgen receptor and is an X-linked recessive trait. We have studied 47 patients with AIS and have characterized the underlying molecular abnormality in the androgen receptor gene. Twenty patients had complete AIS and twenty-seven had partial AIS. Of the latter, 11 were of predominantly female phenotypic appearance and gender was assigned accordingly, while 16 were raised as males. Within the group of complete AIS, two patients had gross deletions within the gene, one had a small deletion, and one had an insertion. In the other patients with complete AIS, as well as all individuals with partial AIS, single nucleotide substitutions within the coding region were detected, each leading to an amino acid alteration. Seven codons were involved in more than one mutation in different cases. In addition, in one patient with spinal and bulbar muscular atrophy, an elongation of a glutamine-repeat was characterized. We conclude that mutations in the androgen receptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist. 18 refs., 2 figs.

  19. Evidence That Androgens Modulate Human Thymic T Cell Output

    Science.gov (United States)

    Olsen, Nancy J.; Kovacs, William J.

    2010-01-01

    Background The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Methods Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs). Cells bearing T cell receptor excision circles (TRECs) were quantitated using real-time PCR amplification of DNA isolated from PBMCs from normal men and from hypogonadal men before and after testosterone replacement therapy. Results CD4+CD45+ (“naïve”) T cells comprised 10.5% of lymphocytes in normal males; this proportion was greatly increased in two hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after one month and to 12.51% after 7 months of normalized androgen levels. In two hypogonadal patients TREC levels fell by 83% and 78% after androgen replacement therapy. Conclusions Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement. PMID:21218609

  20. Steroid receptors and their ligands: Effects on male gamete functions

    International Nuclear Information System (INIS)

    Aquila, Saveria; De Amicis, Francesca

    2014-01-01

    In recent years a new picture of human sperm biology is emerging. It is now widely recognized that sperm contain nuclear encoded mRNA, mitochondrial encoded RNA and different transcription factors including steroid receptors, while in the past sperm were considered incapable of transcription and translation. One of the main targets of steroid hormones and their receptors is reproductive function. Expression studies on Progesterone Receptor, estrogen receptor, androgen receptor and their specific ligands, demonstrate the presence of these systems in mature spermatozoa as surface but also as nuclear conventional receptors, suggesting that both systemic and local steroid hormones, through sperm receptors, may influence male reproduction. However, the relationship between the signaling events modulated by steroid hormones and sperm fertilization potential as well as the possible involvement of the specific receptors are still controversial issues. The main line of this review highlights the current research in human sperm biology examining new molecular systems of response to the hormones as well as specific regulatory pathways controlling sperm cell fate and biological functions. Most significant studies regarding the identification of steroid receptors are reported and the mechanistic insights relative to signaling pathways, together with the change in sperm metabolism energy influenced by steroid hormones are discussed.The reviewed evidences suggest important effects of Progesterone, Estrogen and Testosterone and their receptors on spermatozoa and implicate the involvement of both systemic and local steroid action in the regulation of male fertility potential. - Highlights: • One of the main targets of steroid hormones and their receptors is reproductive function. • Pg/PR co-work to stimulate enzymatic activities to sustain a capacitation process. • E2/ERs regulate sperm motility, capacitation and acrosome reaction and act as survival factors. • Androgens

  1. Steroid receptors and their ligands: Effects on male gamete functions

    Energy Technology Data Exchange (ETDEWEB)

    Aquila, Saveria; De Amicis, Francesca, E-mail: francesca.deamicis@unical.it

    2014-11-01

    In recent years a new picture of human sperm biology is emerging. It is now widely recognized that sperm contain nuclear encoded mRNA, mitochondrial encoded RNA and different transcription factors including steroid receptors, while in the past sperm were considered incapable of transcription and translation. One of the main targets of steroid hormones and their receptors is reproductive function. Expression studies on Progesterone Receptor, estrogen receptor, androgen receptor and their specific ligands, demonstrate the presence of these systems in mature spermatozoa as surface but also as nuclear conventional receptors, suggesting that both systemic and local steroid hormones, through sperm receptors, may influence male reproduction. However, the relationship between the signaling events modulated by steroid hormones and sperm fertilization potential as well as the possible involvement of the specific receptors are still controversial issues. The main line of this review highlights the current research in human sperm biology examining new molecular systems of response to the hormones as well as specific regulatory pathways controlling sperm cell fate and biological functions. Most significant studies regarding the identification of steroid receptors are reported and the mechanistic insights relative to signaling pathways, together with the change in sperm metabolism energy influenced by steroid hormones are discussed.The reviewed evidences suggest important effects of Progesterone, Estrogen and Testosterone and their receptors on spermatozoa and implicate the involvement of both systemic and local steroid action in the regulation of male fertility potential. - Highlights: • One of the main targets of steroid hormones and their receptors is reproductive function. • Pg/PR co-work to stimulate enzymatic activities to sustain a capacitation process. • E2/ERs regulate sperm motility, capacitation and acrosome reaction and act as survival factors. • Androgens

  2. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal

    Directory of Open Access Journals (Sweden)

    Tom Hildebrandt

    2018-03-01

    Full Text Available Synthetic androgens (i. e., anabolic-androgenic steroids are the primary component to the majority of problematic appearance and performance enhancing drug (APED use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc. via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

  3. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal.

    Science.gov (United States)

    Hildebrandt, Tom; Heywood, Ashley; Wesley, Daniel; Schulz, Kurt

    2018-01-01

    Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary component to the majority of problematic appearance and performance enhancing drug (APED) use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc.) via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

  4. Extracellular and intracellular steroid binding proteins

    International Nuclear Information System (INIS)

    Wagner, R.K.

    1978-01-01

    Steroid hormone binding proteins can be measured, after the removal of endogenous steroids, as specific complexes with radio-labelled hormones. In this study all the requirements for a quantitative determination of steroid hormone binding proteins are defined. For different methods, agargel electrophoresis, density gradient centrifugation, equilibrium dialysis and polyacrylamide electrophoresis have been evaluated. Agar electrophoresis at low temperature was found to be the simplest and most useful procedure. With this method the dissociation rates of high affinity complexes can be assessed and absolute binding protein concentrations can be determined. The dissociation rates of the oestradiol-oestrogen receptor complex and the R-5020-progestin receptor complex are low (1-2% per h run time.) In contrast, that of complexes between androgen receptor and dihydrotestosterone (17β-hydroxy-5α-androstan-3-one (DHT), progestin receptor and progesterone, corticosteroid binding globulin (CBG) and cortisol or progesterone and sex hormone binding globulin (SHBG) and DHT were hign (16-27% per h run time). Target tissue extracts (cytosols) contain, besides soluble tissue proteins, large amounts of plasma proteins. The extent of this plasma contamination can be determined by measuring the albumin concentration in cytosols by immunodiffusion. In cytosols of 4 different human target tissues the albumin content varied from 20-30% corresponding to an even higher whole plasma concentration. Steroid binding plasma proteins, such as CBG and SHBG are constituents of this containment. (author)

  5. Maternal androgens in egg yolks : Relation with sex, incubation time and embryonic growth

    NARCIS (Netherlands)

    Eising, C.M; Müller, W; Dijkstra, C.; Groothuis, A.G.G.

    2003-01-01

    Hormones of maternal origin are known to be transferred to the egg yolks of oviparous species. Several studies have shown that within and between clutch variation of maternal androgens may be adaptively tuned. Moreover, it has recently been hypothesized that sex steroids of maternal origin may play

  6. Steroids (For Parents)

    Science.gov (United States)

    ... build muscle, steroids can have very serious side effects. Using steroids for a long time can harm the reproductive ... Teen girls and women risk these additional side effects: male-type facial and body ... risks, kids who use steroids without a prescription are breaking the law. Drug ...

  7. Marine polar steroids

    International Nuclear Information System (INIS)

    Stonik, Valentin A

    2001-01-01

    Structures, taxonomic distribution and biological activities of polar steroids isolated from various marine organisms over the last 8-10 years are considered. The peculiarities of steroid biogenesis in the marine biota and their possible biological functions are discussed. Syntheses of some highly active marine polar steroids are described. The bibliography includes 254 references.

  8. Expression, purification and crystallization of the ancestral androgen receptor-DHT complex.

    Science.gov (United States)

    Colucci, Jennifer K; Ortlund, Eric A

    2013-09-01

    Steroid receptors (SRs) are a closely related family of ligand-dependent nuclear receptors that mediate the transcription of genes critical for development, reproduction and immunity. SR dysregulation has been implicated in cancer, inflammatory diseases and metabolic disorders. SRs bind their cognate hormone ligand with exquisite specificity, offering a unique system to study the evolution of molecular recognition. The SR family evolved from an estrogen-sensitive ancestor and diverged to become sensitive to progestagens, corticoids and, most recently, androgens. To understand the structural mechanisms driving the evolution of androgen responsiveness, the ancestral androgen receptor (ancAR1) was crystallized in complex with 5α-dihydrotestosterone (DHT) and a fragment of the transcriptional mediator/intermediary factor 2 (Tif2). Crystals diffracted to 2.1 Å resolution and the resulting structure will permit a direct comparison with its progestagen-sensitive ancestor, ancestral steroid receptor 2 (AncSR2).

  9. Selection for rapid embryo development correlates with embryo exposure to maternal androgens among passerine birds.

    Science.gov (United States)

    Schwabl, Hubert; Palacios, Maria G; Martin, Thomas E

    2007-08-01

    Greater offspring predation favors evolution of faster development among species. We hypothesized that greater offspring predation exerts selection on mothers to increase levels of anabolic androgens in egg yolks to achieve faster development. Here, we tested whether (1) concentrations of yolk androgens in passerine species were associated with offspring predation and (2) embryo and nestling development rates were associated with yolk androgen concentrations. We examined three androgens that increase in potency along the synthesis pathway: androstenedione (A(4)) to testosterone (T) to 5 alpha -dihydrotestosterone (5 alpha -DHT). Concentrations of none of these steroids were related to clutch size; only A(4) was allometrically related to egg volume. Species that experience greater predation showed higher yolk concentrations of T and 5 alpha -DHT. Higher concentrations of T and particularly 5 alpha -DHT were strongly correlated with faster development during the embryo period and less so during the nestling period. Development rates were most strongly correlated with 5 alpha -DHT, suggesting that potency increases along the androgen synthesis pathway and that effects are mediated by the androgen receptor pathway. These results are consistent with the hypothesis that selection for faster development by time-dependent offspring mortality may be achieved epigenetically by varying embryo exposure to maternal anabolic steroids.

  10. Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat.

    Science.gov (United States)

    Qaiser, M Zeeshan; Dolman, Diana E M; Begley, David J; Abbott, N Joan; Cazacu-Davidescu, Mihaela; Corol, Delia I; Fry, Jonathan P

    2017-09-01

    Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found 3 H-PregS to enter more rapidly than 3 H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of 3 H-DHEAS and 3 H-PregS; a further reduction was seen upon the addition of unlabelled steroid sulphate, suggesting a saturable uptake transporter. Analysis of brain fractions after 0.5 min perfusion with the 3 H-steroid sulphates showed no further metabolism of PregS beyond the liberation of free steroid pregnenolone. By contrast, DHEAS underwent 17-hydroxylation to form androstenediol in both the steroid sulphate and the free steroid fractions, with some additional formation of androstenedione in the latter. Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory. © 2017 International Society for Neurochemistry.

  11. Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography-tandem mass spectrometry method

    DEFF Research Database (Denmark)

    Courant, Frédérique; Aksglæde, Lise; Antignac, Jean-Philippe

    2010-01-01

    Estrogens and androgens play key roles for pubertal onset and sexual maturation. Most currently used immunoassays are not sensitive enough to accurately measure the low circulating levels of sex steroids in children without any signs of puberty. However, this does not exclude that sex steroids ha...

  12. Prevalência do uso e conhecimento de esteroides anabolizantes androgênicos por estudantes e professores de educação física que atuam em academias de ginástica Prevalence of the use of anabolic androgenic steroids by physical education students and teachers who work in health clubs

    Directory of Open Access Journals (Sweden)

    Odilon Salim Costa Abrahin

    2013-02-01

    Full Text Available INTRODUÇÃO: Os esteroides anabólicos androgênicos (EAA são substâncias, quimicamente semelhantes à testosterona, utilizadas para o tratamento/controle de diversas doenças. Contudo, tais substâncias estão sendo empregadas de forma não terapêutica e indiscriminada com finalidades de melhora da performance esportiva e principalmente estética. OBJETIVO: analisar a prevalência do uso e o conhecimento de EAA por estudantes e professores de educação física que atuam em academias de ginástica de Belém, PA. Utilizou-se para a coleta de dados um questionário fechado e anônimo, aplicado a 117 pesquisados. A comparação da prevalência do uso e o grau de conhecimento dos pesquisados sobre EAA foi realizada através de estatística não paramétrica, prova de X² (Qui-quadrado, considerando o intervalo de confiança de 95% e p Anabolic androgenic steroids (AAS are chemically similar to testosterone, used for the treatment/control of various diseases. However, these substances are being used in non-therapeutic and indiscriminate purposes to improve sports performance and mainly esthetics. This study aimed to analyze the prevalence of AAS use and information of undergraduates and physical education teachers working in fitness centers in Belém-PA. A closed anonymous questionnaire was applied to 117 volunteers as an instrument. Comparison of the prevalence of use and degree of information of the respondents about AAS was performed using statistical non-parametric test X² (chi-square, considering the range of 95%, significant when p<0.05. The average age of the participants was 28.0 ± 6.3 years and the prevalence of AAS use was of 31.6%. The highest prevalence found was among specialist professionals (39.3%, the main motivation for the use of AAS was 75.6% to esthetics. Regarding the information, it was found that the drugs were classified as AAS: Durateston, Deca-Durabolin, Oxandrolona/Winstrol. However, these professionals took other

  13. Prenatal Androgen Exposure Causes Hypertension and Gut Microbiota Dysbiosis.

    Science.gov (United States)

    Sherman, Shermel; Sarsour, Nadeen; Salehi, Marziyeh; Schroering, Allen; Mell, Blair; Joe, Bina; Hill, Jennifer W

    2018-02-22

    Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring. The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs). We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in

  14. Senp1 Is Essential for Desumoylating Sumo1-Modified Proteins but Dispensable for Sumo2 and Sumo3 Deconjugation in the Mouse Embryo

    Directory of Open Access Journals (Sweden)

    Prashant Sharma

    2013-05-01

    Full Text Available Posttranslational modification with small ubiquitin-like modifier (Sumo regulates numerous cellular and developmental processes. Sumoylation is dynamic with deconjugation by Sumo-specific proteases (Senps regulating steady-state levels. Different Senps are found in distinct subcellular domains, which may limit their deconjugation activity to colocalizing Sumo-modified proteins. In vitro, Senps can discriminate between the different Sumo paralogs: Sumo1 versus the highly related Sumo2 and Sumo3 (Sumo2/3, which can form poly-Sumo chains. However, a full understanding of Senp specificity in vivo is still lacking. Here, using biochemical and genetic approaches, we establish that Senp1 has an essential, nonredundant function to desumoylate Sumo1-modified proteins during mouse embryonic development. Senp1 specificity for Sumo1 conjugates represents an intrinsic function and not simply a product of colocalization. In contrast, Senp1 has only a limited role in Sumo2/3 desumoylation, although it may regulate Sumo1-mediated termination of poly-Sumo2/3 chains.

  15. Effects of anabolic-androgens on brain reward function

    Directory of Open Access Journals (Sweden)

    Emanuela eMhillaj

    2015-08-01

    Full Text Available Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming the so called androgen anabolic steroids (AAS. These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, the off-label utilization is very wide. Furthermore, combination of different steroids, and doses largely higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. Among the AAS abusers, the frequency of side effects is higher, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because the collection of data is very difficult due to reticent subjects and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in reward process, leading to an increased sensitivity toward opioid narcotics and central stimulants. The aim of this review is to discuss what is present in literature in regard to steroid abuse and alteration of reward system in preclinical and clinical studies.

  16. Uxoricide and dismemberment in a case of illicit anabolic steroid use: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Allan Seppänen

    2016-12-01

    Full Text Available Despite abounding evidence for the harmful effects of synthetic anabolic-androgenic steroids, they are commonly misused for competitive and body-image reasons. Steroids are often used in the context of poly-drug misuse, which may mask their specific effects on behaviour, such as increasing aggression. We present our case report as a concrete example of current steroid-related substance-misuse trends. A 25-year old Finnish male with various psychiatric and drug-related symptomology, but almost no previous history of aggressive behaviour, battered his wife to death and mutilated her body after a five-week steroid regimen.

  17. EVALUATION OF THE EFFECTS OF ENVIRONMENTAL COMPOUNDS ON STEROID HORMONE PRODUCTION IN H295R CELLS

    Science.gov (United States)

    H295R cells constitute a pluripotent cell line that has retained the enzymatic ability to produce steroids along the entire steroidogenic pathway, including C19 androgens and C18 estrogens. For this reason, they have been a valued research tool, and have been employed in an ever...

  18. Novel approach to the preparation of hemisuccinates of steroids bearing tertiary alcohol group

    Czech Academy of Sciences Publication Activity Database

    Longin, O.; Černý, Ivan; Drašar, P.

    2015-01-01

    Roč. 97, SI (2015), s. 67-71 ISSN 0039-128X Grant - others:GA MV(CZ) VG20112015045 Institutional support: RVO:61388963 Keywords : anabolic-androgenic steroid * ester formation * hemisuccinate * tertiary alcohol Subject RIV: CE - Biochemistry Impact factor: 2.513, year: 2015

  19. Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Claire [CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31000 (France); Universite de Toulouse, UPS, IPBS, Toulouse F-31000 (France); Lafosse, Jean-Michel [CHU Toulouse, Hopital Rangueil, Service d' orthopedie et Traumatologie, Toulouse F-31000 (France); Malavaud, Bernard [CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31000 (France); Universite de Toulouse, UPS, IPBS, Toulouse F-31000 (France); CHU Toulouse, Hopital Rangueil, Service d' Urologie et de Transplantation Renale, Toulouse F-31000 (France); Cuvillier, Olivier, E-mail: olivier.cuvillier@ipbs.fr [CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31000 (France); Universite de Toulouse, UPS, IPBS, Toulouse F-31000 (France)

    2010-01-01

    Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relied on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists could block SphK1 stimulation by DHT and its consequences. Finally, SphK1 inhibition not only abrogated DHT-induced ERK activation but also blocked cell proliferation, while ERK inhibition had no impact, suggesting that SphK1 was critical for DHT signaling yet independently of the ERK.

  20. Selective androgen receptor modulators in preclinical and clinical development.

    Science.gov (United States)

    Narayanan, Ramesh; Mohler, Michael L; Bohl, Casey E; Miller, Duane D; Dalton, James T

    2008-01-01

    Androgen receptor (AR) plays a critical role in the function of several organs including primary and accessory sexual organs, skeletal muscle, and bone, making it a desirable therapeutic target. Selective androgen receptor modulators (SARMs) bind to the AR and demonstrate osteo- and myo-anabolic activity; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents produce less of a growth effect on prostate and other secondary sexual organs. SARMs provide therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, or end-stage renal disease, osteoporosis, frailty, and hypogonadism. This review summarizes the current standing of research and development of SARMs, crystallography of AR with SARMs, plausible mechanisms for their action and the potential therapeutic indications for this emerging class of drugs.

  1. Cortical venous thrombosis following exogenous androgen use for bodybuilding.

    Science.gov (United States)

    Sveinsson, Olafur; Herrman, Lars

    2013-02-05

    There are only a few reports of patients developing cerebral venous sinus thrombosis (CVST) after androgen therapy. We present a young man who developed cortical venous thrombosis after using androgens to increase muscle mass. He was hospitalised for parasthesia and dyspraxia in the left hand followed by a generalised tonic-clonic seizure. At admission, he was drowsy, not fully orientated, had sensory inattention, pronation drift and a positive extensor response, all on the left side. The patient had been using anabolic steroids (dainabol 20 mg/day) for the last month for bodybuilding. CT angiography showed a right cortical venous thrombosis. Anticoagulation therapy was started with intravenous heparin for 11 days and oral anticoagulation (warfarin) thereafter. A control CT angiography 4 months later showed resolution of the thrombosis. He recovered fully.

  2. Steroid hormone profile in female polar bears (Ursus maritimus)

    DEFF Research Database (Denmark)

    Gustavson, Lisa; Jenssen, Bjørn Munro; Bytingsvik, Jenny

    2015-01-01

    The polar bear is an iconic Arctic species, threatened by anthropogenic impacts such as pollution and climate change. Successful reproduction of polar bears depends on a functioning steroid hormone system, which is susceptible to effects of persistent organic pollutants. The present study...... is the first study to report circulating concentrations of nine steroid hormones (i.e., estrogens, androgens and progestagens) in female polar bears (Ursus maritimus). The aim of the study was to investigate the effects of age, condition, location and reproductive status on steroid profile in female polar...... bears. Levels of pregnenolone (PRE), progesterone, androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone, dihydrotestosterone, estrone (E1), 17α-estradiol (αE2) and 17β-estradiol (βE2) were quantified in blood (serum) of free-living female polar bears (n = 15) from Svalbard, Norway, by gas...

  3. Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

    Directory of Open Access Journals (Sweden)

    Nicolas Diotel

    2018-02-01

    Full Text Available Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals. In this review, we will first document neurosteroidogenesis and steroid signaling for estrogens, progestagens, and androgens in the brain of teleost fish, birds, and mammals. We will next consider the effects of sex steroids in homeostatic and regenerative neurogenesis, in neuroprotection, and in sexual behaviors. In a last part, we will discuss the transport of steroids and lipoproteins from the periphery within the brain (and vice-versa and document their effects on the blood-brain barrier (BBB permeability and on neuroprotection. We will emphasize the potential interaction between lipoproteins and sex steroids, addressing the beneficial effects of steroids and lipoproteins, particularly HDL-cholesterol, against the breakdown of the BBB reported to occur during brain ischemic stroke. We will consequently highlight the potential anti-inflammatory, anti-oxidant, and neuroprotective properties of sex steroid and lipoproteins, these latest improving cholesterol and steroid ester transport within the brain after insults.

  4. Revisiting hyper- and hypo-androgenism by tandem mass spectrometry.

    Science.gov (United States)

    Fanelli, Flaminia; Gambineri, Alessandra; Mezzullo, Marco; Vicennati, Valentina; Pelusi, Carla; Pasquali, Renato; Pagotto, Uberto

    2013-06-01

    Modern endocrinology is living a critical age of transition as far as laboratory testing and biochemical diagnosis are concerned. Novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for steroid measurement in biological fluids have abundantly demonstrated their analytical superiority over immunometric platforms that until now have dominated the world of steroid hormones determination in clinical laboratories. One of the most useful applications of LC-MS/MS is in the hypogonadism and hyperandrogenism field: LC-MS/MS has proved particularly suitable for the detection of low levels of testosterone typical of women and children, and in general more reliable in accurately determining hypogonadal male levels. This technique also offers increased informative power by allowing multi-analytical profiles that give a more comprehensive picture of the overall hormonal asset. Several LC-MS/MS methods for testosterone have been published in the last decade, some of them included other androgen or more comprehensive steroid profiles. LC-MS/MS offers the concrete possibility of achieving a definitive standardization of testosterone measurements and the generation of widely accepted reference intervals, that will set the basis for a consensus on the diagnostic value of biochemical testing. The present review is aimed at summarizing technological advancements in androgen measurements in serum and saliva. We also provide a picture of the state of advancement of standardization of testosterone assays, of the redefinition of androgen reference intervals by novel assays and of studies using LC-MS/MS for the characterization and diagnosis of female hyperandrogenism and male hypogonadism.

  5. Screening of synthetic and natural product databases: Identification of novel androgens and antiandrogens.

    Science.gov (United States)

    Bobach, Claudia; Tennstedt, Stephanie; Palberg, Kristin; Denkert, Annika; Brandt, Wolfgang; de Meijere, Armin; Seliger, Barbara; Wessjohann, Ludger A

    2015-01-27

    The androgen receptor is an important pharmaceutical target for a variety of diseases. This paper presents an in silico/in vitro screening procedure to identify new androgen receptor ligands. The two-step virtual screening procedure uses a three-dimensional pharmacophore model and a docking/scoring routine. About 39,000 filtered compounds were docked with PLANTS and scored by Chemplp. Subsequent to virtual screening, 94 compounds, including 28 steroidal and 66 nonsteroidal compounds, were tested by an androgen receptor fluorescence polarization ligand displacement assay. As a result, 30 compounds were identified that show a relative binding affinity of more than 50% in comparison to 100 nM dihydrotestosterone and were classified as androgen receptor binders. For 11 androgen receptor binders of interest IC50 and Ki values were determined. The compound with the highest affinity exhibits a Ki value of 10.8 nM. Subsequent testing of the 11 compounds in a PC-3 and LNCaP multi readout proliferation assay provides insights into the potential mode of action. Further steroid receptor ligand displacement assays and docking studies on estrogen receptors α and β, glucocorticoid receptor, and progesterone receptor gave information about the specificity of the 11 most active compounds. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Structural and biochemical properties of cloned and expressed human and rat steroid 5α-reductases

    International Nuclear Information System (INIS)

    Andersson, S.; Russell, D.W.

    1990-01-01

    The microsomal enzyme steroid 5α-reductase is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone. In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Here we describe the isolation, structure, and expression of a cDNA encoding the human steroid 5α-reductase. A rat cDNA was used as a hybridization probe to screen a human prostate cDNA library. A 2.1-kilobase cDNA was identified and DNA sequence analysis indicated that the human steroid 5α-reductase was a hydrophobic protein of 259 amino acids with a predicted molecular weight of 29,462. A comparison of the human and rat protein sequences revealed a 60% identity. Transfection of expression vectors containing the human and rat cDNAs into simian COS cells resulted in the synthesis of high levels of steroid 5α-reductase enzyme activity. Both enzymes expressed in COS cells showed similar substrate specificities for naturally occurring steroid hormones. However, synthetic 4-azasteroids demonstrated marked differences in their abilities to inhibit the human and rat steroid 5α-reductases

  7. Network analysis of an in vitro model of androgen-resistance in prostate cancer

    International Nuclear Information System (INIS)

    Detchokul, Sujitra; Elangovan, Aparna; Crampin, Edmund J.; Davis, Melissa J.; Frauman, Albert G.

    2015-01-01

    The development of androgen resistance is a major limitation to androgen deprivation treatment in prostate cancer. We have developed an in vitro model of androgen-resistance to characterise molecular changes occurring as androgen resistance evolves over time. Our aim is to understand biological network profiles of transcriptomic changes occurring during the transition to androgen-resistance and to validate these changes between our in vitro model and clinical datasets (paired samples before and after androgen-deprivation therapy of patients with advanced prostate cancer). We established an androgen-independent subline from LNCaP cells by prolonged exposure to androgen-deprivation. We examined phenotypic profiles and performed RNA-sequencing. The reads generated were compared to human clinical samples and were analysed using differential expression, pathway analysis and protein-protein interaction networks. After 24 weeks of androgen-deprivation, LNCaP cells had increased proliferative and invasive behaviour compared to parental LNCaP, and its growth was no longer responsive to androgen. We identified key genes and pathways that overlap between our cell line and clinical RNA sequencing datasets and analysed the overlapping protein-protein interaction network that shared the same pattern of behaviour in both datasets. Mechanisms bypassing androgen receptor signalling pathways are significantly enriched. Several steroid hormone receptors are differentially expressed in both datasets. In particular, the progesterone receptor is significantly differentially expressed and is part of the interaction network disrupted in both datasets. Other signalling pathways commonly altered in prostate cancer, MAPK and PI3K-Akt pathways, are significantly enriched in both datasets. The overlap between the human and cell-line differential expression profiles and protein networks was statistically significant showing that the cell-line model reproduces molecular patterns observed in

  8. Steroids in neuroinfection

    Directory of Open Access Journals (Sweden)

    Ronaldo Abraham

    2013-09-01

    Full Text Available The consequences of inflammatory response are primarily responsible for morbimortality in bacterial meningitis. Early use of steroids in these cases can reduce mortality and hearing loss and improve functional outcome without causing significant side effects. The formal recommendation towards pneumoccocal meningitis is being extended to other forms of Bacterial Meningitis. The same thought can be applied to tuberculous meningitis. In neurocysticercosis and neuroschistosomiasis steroids are more useful than parasiticides in most cases. Despite the evidence favoring the use of steroids in herpes simplex encephalitis, it is not sufficient to definitely support such indication. Among the opportunistic infections that affect AIDS patients, neurotoxoplasmosis and progressive multifocal leukoencephalopaty are those most often considered for the use of steroids; steroids are safe to use, but no definite benefit could be demonstrated in both conditions.

  9. Adjunctive steroid treatment

    DEFF Research Database (Denmark)

    Korshin, André; Køster-Rasmussen, Rasmus; Meyer, Christian N

    2007-01-01

    Our objective was to evaluate local guidelines regarding early steroid treatment in adult community acquired bacterial meningitis, and assess the actual treatment given and its correlation to clinical outcome. Patient outcome was obtained retrospectively from the medical records of 210 adults...... admitted to 47 hospitals in Denmark during 2002-2004 (population 5.4 million) and was combined with results from a questionnaire regarding treatment guidelines in these hospitals. In 36 of 47 departments responding to the questionnaire, 21 recommended early steroid treatment, but none did so initially...... during 2002. Early steroid treatment was given to 15% of patients and was given more often when recommended locally (41% vs 11%, OR=5.7 (2.4-13.5)). Unfavourable outcome was demonstrated rarely in patients treated with early steroids compared to the non-steroid group (17% vs 42%, p

  10. Effects of triazole fungicides on androgenic disruption and CYP3A4 enzyme activity.

    Science.gov (United States)

    Lv, Xuan; Pan, Liumeng; Wang, Jiaying; Lu, Liping; Yan, Weilin; Zhu, Yanye; Xu, Yiwen; Guo, Ming; Zhuang, Shulin

    2017-03-01

    Triazole fungicides are widely used as broad-spectrum fungicides, non-steroidal antiestrogens and for various industrial applications. Their residues have been frequently detected in multiple environmental and human matrices. The increasingly reported toxicity incidents have led triazole fungicides as emerging contaminants of environmental and public health concern. However, whether triazole fungicides behave as endocrine disruptors by directly mimicking environmental androgens/antiandrogens or exerting potential androgenic disruption indirectly through the inhibition of cytochrome P450 (CYP450) enzyme activity is yet an unresolved question. We herein evaluated five commonly used triazole fungicides including bitertanol, hexaconazole, penconazole, tebuconazole and uniconazole for the androgenic and anti-androgenic activity using two-hybrid recombinant human androgen receptor (AR) yeast bioassay and comparatively evaluated their effects on enzymatic activity of CYP3A4 by P450-Glo™ CYP3A4 bioassay. All five fungicides showed moderate anti-androgenic activity toward human AR with the IC 50 ranging from 9.34 μM to 79.85 μM. The anti-androgenic activity remained no significant change after the metabolism mediated by human liver microsomes. These fungicides significantly inhibited the activity of CYP3A4 at the environmental relevant concentrations and the potency ranks as tebuconazole > uniconazole > hexaconazole > penconazole > bitertanol with the corresponding IC 50 of 0.81 μM, 0.93 μM, 1.27 μM, 2.22 μM, and 2.74 μM, respectively. We found that their anti-androgenic activity and the inhibition potency toward CYP3A4 inhibition was significantly correlated (R 2 between 0.83 and 0.97, p pesticides and structurally similar chemicals should fully consider potential androgenic disrupting effects and the influences on the activity of CYP450s. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Nonsteroidal selective androgen receptor modulators enhance female sexual motivation.

    Science.gov (United States)

    Jones, Amanda; Hwang, Dong Jin; Duke, Charles B; He, Yali; Siddam, Anjaiah; Miller, Duane D; Dalton, James T

    2010-08-01

    Women experience a decline in estrogen and androgen levels after natural or surgically induced menopause, effects that are associated with a loss of sexual desire and bone mineral density. Studies in our laboratories have shown the beneficial effects of selective androgen receptor modulators (SARMs) in the treatment of osteoporosis and muscle wasting in animal models. A series of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-cyano-3-trifluoromethyl-phenyl)-propionamide analogs was synthesized to evaluate the effects of B-ring substitutions on in vitro and in vivo pharmacologic activity, especially female sexual motivation. The androgen receptor (AR) relative binding affinities ranged from 0.1 to 26.5% (relative to dihydrotestosterone) and demonstrated a range of agonist activity at 100 nM. In vivo pharmacologic activity was first assessed by using male rats. Structural modifications to the B-ring significantly affected the selectivity of the SARMs, demonstrating that single-atom substitutions can dramatically and unexpectedly influence activity in androgenic (i.e., prostate) and anabolic (i.e., muscle) tissues. (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro,4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide (S-23) displayed full agonist activity in androgenic and anabolic tissues; however, the remaining SARMs were more prostate-sparing, selectively maintaining the size of the levator ani muscle in castrated rats. The partner-preference paradigm was used to evaluate the effects of SARMs on female sexual motivation. With the exception of two four-halo substituted analogs, the SARMs increased sexual motivation in ovariectomized rats, with potency and efficacy comparable with testosterone propionate. These results indicate that the AR is important in regulating female libido given the nonaromatizable nature of SARMs and it could be a superior alternative to steroidal testosterone preparations in the treatment of hypoactive sexual desire disorder.

  12. Update of monotherapy trials with the new anti-androgen, Casodex (ICI 176,334). International Casodex Investigators

    DEFF Research Database (Denmark)

    Iversen, P

    1994-01-01

    Casodex (ICI 176,334) is a non-steroidal anti-androgen, which has a half-life compatible with once-daily oral dosing. In an open, phase II study on 267 patients given Casodex, 50 mg/day, an overall objective response (i.e. partial regression) was seen in 55.5% of patients (146 of 263) with a furt...

  13. The prohibitin-repressive interaction with E2F1 is rapidly inhibited by androgen signalling in prostate cancer cells

    NARCIS (Netherlands)

    Koushyar, S.; Economides, G.; Zaat, S.; Jiang, W.; Bevan, C. L.; Dart, D. A.

    2017-01-01

    Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities across several cellular compartments including mitochondria, cell membrane and the nucleus. PHB and the steroid-activated androgen receptor (AR) have an interplay where AR downregulates PHB, and PHB represses AR.

  14. [7α-18F]fluoro-17α-methyl-5α-dihydrotestosterone: a ligand for androgen receptor-mediated imaging of prostate cancer

    International Nuclear Information System (INIS)

    Garg, Pradeep K.; Labaree, David C.; Hoyte, Robert M.; Hochberg, Richard B.

    2001-01-01

    We have synthesized a 18 F-labeled androgen, [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone, in a no-carrier-added radiosynthesis by exchange of 18 F- (tetrabutylammonium fluoride) with the 7β-tosyloxy of 17α-methyl-5α-dihydrotestosterone. The nonradioactive steroid binds with high affinity and specificity to the androgen receptor and binds poorly, if at all, to other steroid receptors and plasma sex hormone binding globulin. The 7α- 18 F-androgen concentrates markedly in the prostate of rats by an androgen receptor-dependent mechanism. It is likely that [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone will be an excellent positron emission tomography imaging agent for prostate cancer

  15. Specific interaction of radioactive anti-androgen TSAA-291 with androgen receptor in rat prostates

    International Nuclear Information System (INIS)

    Sudo, K.; Yoshida, K.; Nakayama, R.

    1982-01-01

    A steroidal anti-androgen TSSA-291 (16β-ethyl-17β-hydroxy-4-oestren-3-one) bound to a macromolecular component in the cytosol of rat ventral prostates with high affinity (Kdsub(d) = 5.0 x 10 -9 M) and in a saturable manner. The number of binding sites was comparable to that for 5α-dihydrotestosterone (5α-DHT). [ 3 H]TSAA-291 binding was effectively displaced by unlabelled 5α-DHT, 19-nortestosterone and cyproterone acetate but to a lesser degree by corticosterone. Glycerol density-gradient centrifugation analysis revealed that the sedimentation coefficient of the [ 3 H]-TSAA-291-macromolecule complex was 3-4.5 S. However, when the unlabelled cytosol was fractionated by glycerol density-gradient centrifugation before the binding of [ 3 H]TSAA-291 was examined, specific binding of [ 3 H]TSAA-291 was observed in fractions corresponding to 8-10 S. Binding of the [ 3 H]TSAA-291-macromolecules comples to prostatic nuclei and DNA-cellulose was considerably less than binding by the [ 3 H]5α-DHT-macromolecule complex. Instability of the TSAA-291 binding coponent on heat treatment before and after complex formation was also revealed and the results are discussed in terms of the anti-androgenic activity of TSAA-291. (author)

  16. Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications.

    Science.gov (United States)

    Lucas-Herald, Angela K; Alves-Lopes, Rheure; Montezano, Augusto C; Ahmed, S Faisal; Touyz, Rhian M

    2017-07-01

    The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Androgens are essential for many developmental and physiological processes, especially in male reproductive tissues. It is now clear that androgens have multiple actions besides sex differentiation and sexual maturation and that many physiological systems are influenced by androgens, including regulation of cardiovascular function [nitric oxide (NO) release, Ca 2+ mobilization, vascular apoptosis, hypertrophy, calcification, senescence and reactive oxygen species (ROS) generation]. This review focuses on evidence indicating that interplay between genomic and non-genomic actions of testosterone may influence cardiovascular function. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  17. Zebrafish (Danio rerio) androgen receptor: sequence homology and up-regulation by the fungicide vinclozolin.

    Science.gov (United States)

    Smolinsky, Amanda N; Doughman, Jennifer M; Kratzke, Liên-Thành C; Lassiter, Christopher S

    2010-03-01

    Steroid hormones regulate gene expression in organisms by binding to receptor proteins. These hormones include the androgens, which signal through androgen receptors (ARs). Endocrine disrupters (EDCs) are chemicals in the environment that adversely affect organisms by binding to nuclear receptors, including ARs. Vinclozolin, a fungicide used on fruit and vegetable crops, is a known anti-androgen, a type of EDC that blocks signals from testosterone and its derivatives. In order to better understand the effects of EDCs, further research on androgen receptors and other hormone signaling pathways is necessary. In this study, we demonstrate the evolutionary conservation between the genomic structure of the human and zebrafish ar genes and find that ar mRNA expression increases in zebrafish embryos exposed to vinclozolin, which may be evolutionarily conserved as well. At 48 and 72 h post-fertilization, vinclozolin-treated embryos express ar mRNA 8-fold higher than the control level. These findings suggest that zebrafish embryos attempt to compensate for the presence of an anti-androgen by increasing the number of androgen receptors available.

  18. Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

    Science.gov (United States)

    Kuuranne, Tiia; Saugy, Martial; Baume, Norbert

    2014-01-01

    In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module. PMID:24764553

  19. Androgens and polycystic ovary syndrome.

    Science.gov (United States)

    Nisenblat, Vicki; Norman, Robert J

    2009-06-01

    Polycystic ovary syndrome (PCOS) is a common complex endocrine genetic disorder, which involves overproduction of androgens, leading to heterogeneous range of symptoms and associated with increased metabolic and cardiovascular morbidity. This review focuses on androgen biosynthesis, use, metabolism in PCOS and clinical consequences of hyperandrogenism. Controversial definition of the disorder and different phenotypic subgroups present a challenge for clinical and basic research. Further investigation of different phenotypes highlights the fact that PCOS probably represents a group of disorders with different etiologies. Prenatal androgen exposure and adolescent studies suggest early in life androgen excess as initiating factor of PCOS, but insufficient evidence available to confirm this hypothesis. Various intracellular signaling pathways implicated in PCOS steroidogenesis and in androgen action have been studied, however, PCOS pathogenesis remains obscure. Growing evidence links androgens with pathophysiology of PCOS and metabolic derangements. Despite intensive investigation, etiology and underlying mechanisms of PCOS remain unclear, warranting further investigation. Better understanding of molecular and genetic basis might lead to invention of novel therapeutic approaches. Long-term interventional studies that lower androgen levels in women with hyperandrogenism might protect against metabolic and cardiovascular comorbidities are needed.

  20. In vivo detection of fluctuating brain steroid levels SHORT

    Science.gov (United States)

    Ikeda, Maaya; Rensel, Michelle A.; Schlinger, Barney A.; Remage-Healey, Luke

    2015-01-01

    This protocol describes a method for in vivo measurement of steroid hormones in brain circuits of the zebra finch. In vivo microdialysis has been used successfully to detect fluctuating neurosteroids in the auditory forebrain (Remage-Healey et al., 2008; 2012; Ikeda et al., 2012) and in the hippocampus (Rensel et al., 2012; 2013) of behaving adult zebra finches. In some cases, the steroids measured are derived locally (e.g., ‘neurosteroids’ like estrogens in males) whereas in other cases the steroids measured reflect systemic circulating levels and/or central conversion (e.g., the primary androgen testosterone and the primary glucocorticoid corticosterone). We also describe the method of reverse-microdialysis (‘retrodialysis’) of compounds that can influence local steroid neurochemistry as well as behavior. In vivo microdialysis can now be used to study steroid signaling in the brain for a variety of experimental purposes. Furthermore, similar methods have been developed to examine changing levels of catecholamines in behaving zebra finches (e.g., Sasaki et al., 2006). Thus, the combined study of neurochemistry and behavior in a vocal learning species now has a new set of powerful tools. PMID:25342066

  1. Drug Facts: Anabolic Steroids

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  2. Anabolic Steroids (For Teens)

    Science.gov (United States)

    ... the percentage of teens who misuse steroids. Swipe left or right to scroll. Monitoring the Future Study: Trends in ... Drugs of Abuse Discover what happens to the brain on drugs. ... vs. drug use. Read More » 92 Comments Dopers Downfall ...

  3. Selective androgen receptor modulators as function promoting therapies.

    Science.gov (United States)

    Bhasin, Shalender; Jasuja, Ravi

    2009-05-01

    The past decade has witnessed an unprecedented discovery effort to develop selective androgen receptor modulators (SARMs) that improve physical function and bone health without adversely affecting the prostate and cardiovascular outcomes. This review describes the historical evolution, the rationale for SARM development, and the mechanisms of testosterone action and SARM selectivity. Although steroidal SARMs have been around since the 1940s, a number of nonsteroidal SARMs that do not serve as substrates for CYP19 aromatase or 5alpha-reductase, act as full agonists in muscle and bone and as partial agonists in prostate are in development. The differing interactions of steroidal and nonsteroidal compounds with androgen receptor (AR) contribute to their unique pharmacologic actions. Ligand binding induces specific conformational changes in the ligand-binding domain, which could modulate surface topology and protein-protein interactions between AR and coregulators, resulting in tissue-specific gene regulation. Preclinical studies have demonstrated the ability of SARMs to increase muscle and bone mass in preclinical rodent models with varying degree of prostate sparing. Phase I trials of SARMs in humans have reported modest increments in fat-free mass. SARMs hold promise as a new class of function promoting anabolic therapies for a number of clinical indications, including functional limitations associated with aging and chronic disease, frailty, cancer cachexia, and osteoporosis.

  4. Inhibitors of steroidal cytochrome p450 enzymes as targets for drug development.

    Science.gov (United States)

    Baston, Eckhard; Leroux, Frédéric R

    2007-01-01

    Cytochrome P450's are enzymes which catalyze a large number of biological reactions, for example hydroxylation, N-, O-, S- dealkylation, epoxidation or desamination. Their substrates include fatty acids, steroids or prostaglandins. In addition, a high number of various xenobiotics are metabolized by these enzymes. The enzyme 17alpha-hydroxylase-C17,20-lyase (P450(17), CYP 17, androgen synthase), a cytochrome P450 monooxygenase, is the key enzyme for androgen biosynthesis. It catalyzes the last step of the androgen biosynthesis in the testes and adrenal glands and produces androstenedione and dehydroepiandrosterone from progesterone and pregnenolone. The microsomal enzyme aromatase (CYP19) transforms these androgens to estrone and estradiol. Estrogens stimulate tumor growth in hormone dependent breast cancer. In addition, about 80 percent of prostate cancers are androgen dependent. Selective inhibitors of these enzymes are thus important alternatives to treatment options like antiandrogens or antiestrogens. The present article deals with recent patents (focus on publications from 2000 - 2006) concerning P450 inhibitor design where steroidal substrates are involved. In this context a special focus is provided for CYP17 and CYP19. Mechanisms of action will also be discussed. Inhibitors of CYP11B2 (aldosterone synthase) will also be dealt with.

  5. Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

    Science.gov (United States)

    Pappa, Theodora; Alevizaki, Maria

    2012-08-01

    Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

  6. EVALUASI IN VITRO TERHADAP KEMAMPUAN ISOLAT BAKTERI ASAM LAKTAT ASAL AIR SUSU IBU UNTUK MENGASIMILASI KOLESTEROL DAN MENDEKONJUGASI GARAM EMPEDU [In Vitro Evaluation of Cholesterol Assimilation and Bile Salt Deconjugation by Lactic Acid Bacteria Isolated from Breast Milk

    Directory of Open Access Journals (Sweden)

    Lilis Nuraida1,2*

    2011-06-01

    Full Text Available Hypercholesterolemia is a risk factor for cardiovascular disease, the leading cause of death in many countries. Several studies have shown that reduction of excessive levels of cholesterol in the blood decreases the risk of cardiovascular disease. It is therefore important to develop ways of reducing serum cholesterol. Based on in vitro and in vivo studies, some of lactic acid bacteria (LAB having potential probiotic properties can reduce total cholesterol and low-density lipoprotein cholesterol levels. The aim of this study was to evaluate the ability of LAB isolated from breast milk in reducing cholesterol by assimilation and by bile salt deconjugation activity in vitro.Thirteen strains of LABs were evaluated for their acid and bile salt resistance and selected to test their ability to assimilate cholesterol and to deconjugate bile salt (natrium taurocholate in vitro. Cholesterol assimilation activity was determined by measuring the difference between the remaining cholesterol in broth medium inoculated with LAB with cholesterol in control after incubation. Bile salt deconjugation activity was determined by measuring free cholic acid released in broth medium after incubation with LAB. The results shows that most of the isolates was susceptible to low pH and all isolates used were able to survive in the presence of 0.5% bile salt. The LAB were also able to assimilate cholesterol at varying levels ranging from 0.86-14.97 µg/ml, with the highest activity showed by Pediococcus pentosaceus 1-A38, Pediococcus pentosaceus 2-B2 and Pediococcus pentosaceus 2-A16. Taurocholate deconjugation assay showed that the isolates have weak bile salts deconjugation activity as indicated by free cholic acid released ranging from 0.06-0.25 µmol/ml, with the highest release in Pediococcus pentosaceus 1-A38 and Pediococcus pentosaceus 1-A22. The present study suggest that Pediococcus pentosaceus 1-A38 was potential for the development of probiotic products with

  7. Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators.

    Science.gov (United States)

    Bohl, Casey E; Wu, Zengru; Chen, Jiyun; Mohler, Michael L; Yang, Jun; Hwang, Dong Jin; Mustafa, Suni; Miller, Duane D; Bell, Charles E; Dalton, James T

    2008-10-15

    Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit an additional region of hydrogen bonding not seen with steroidal compounds and that multiple halogen substitutions affect the B-ring conformation and aromatic interactions with Trp741. This information elucidates interactions important for high AR binding affinity and provides new insight for structure-based drug design.

  8. Developmental programming: exposure to testosterone excess disrupts steroidal and metabolic environment in pregnant sheep.

    Science.gov (United States)

    Abi Salloum, B; Veiga-Lopez, A; Abbott, D H; Burant, C F; Padmanabhan, V

    2015-06-01

    Gestational exposure to excess T leads to intrauterine growth restriction, low birth weight, and adult metabolic/reproductive disorders in female sheep. We hypothesized that as early mediators of such disruptions, gestational T disrupts steroidal and metabolic homeostasis in both the mother and fetus by both androgenic and metabolic pathways. Maternal blood samples were measured weekly for levels of insulin, glucose, and progesterone from four groups of animals: control; gestational T (twice weekly im injections of 100 mg of T propionate from d 30 to d 90 of gestation); T plus an androgen antagonist, flutamide (15 mg/kg·d oral; T-Flutamide); and T plus the insulin sensitizer, rosiglitazone (0.11 mg/kg·d oral; T-Rosi) (n = 10-12/group). On day 90 of gestation, maternal and umbilical cord samples were collected after a 48-hour fast from a subset (n = 6/group) for the measurement of steroids, free fatty acids, amino acids, and acylcarnitines. Gestational T decreased maternal progesterone levels by 36.5% (P fetal estradiol were not prevented by either cotreatment. Gestational T disrupted associations of steroids with metabolites and progesterone with acylcarnitines, which was prevented either by androgen antagonist or insulin sensitizer cotreatment. These findings suggest a future combination of these treatments might be required to prevent alteration in maternal/fetal steroidal and metabolic milieu(s).

  9. ANDROGEN REPLACEMENT THERAPY IN POSTMENOPAUSE

    Directory of Open Access Journals (Sweden)

    Helena Meden Vrtovec

    2008-12-01

    Scientific studies and clinical experiences have not provided until now the answers to thequestion: »Whom to treat, when, why and for how long should androgens be used for HRTin postmenopausal women?«

  10. MEDICAL ISSUES ASSOCIATED WITH ANABOLIC STEROID USE: ARE THEY EXAGGERATED?

    Directory of Open Access Journals (Sweden)

    Jay R. Hoffman

    2006-06-01

    Full Text Available For the past 50 years anabolic steroids have been at the forefront of the controversy surrounding performance enhancing drugs. For almost half of this time no attempt was made by sports governing bodies to control its use, and only recently have all of the major sports governing bodies in North America agreed to ban from competition and punish athletes who test positive for anabolic steroids. These punitive measures were developed with the primary concern for promotion of fair play and eliminating potential health risks associated with androgenic-anabolic steroids. Yet, controversy exists whether these testing programs deter anabolic steroid use. Although the scope of this paper does not focus on the effectiveness of testing, or the issue of fair play, it is of interest to understand why many athletes underestimate the health risks associated from these drugs. What creates further curiosity is the seemingly well-publicized health hazards that the medical community has depicted concerning anabolic steroidabuse. Is there something that the athletes know, or are they simply naïve regarding the dangers? The focus of this review is to provide a brief history of anabolic steroid use in North America, the prevalence of its use in both athletic and recreational populations and its efficacy. Primary discussion will focus on health issues associated with anabolic steroid use with an examination of the contrasting views held between the medical community and the athletes that are using these ergogenic drugs. Existing data suggest that in certain circumstances the medical risk associated with anabolic steroid use may have been somewhat exaggerated, possibly to dissuade use in athletes

  11. Relationships between POPs, biometrics and circulating steroids in male polar bears (Ursus maritimus) from Svalbard.

    Science.gov (United States)

    Ciesielski, Tomasz M; Hansen, Ingunn Tjelta; Bytingsvik, Jenny; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M; Styrishave, Bjarne

    2017-11-01

    The aim of this study was to determine the effects of persistent organic pollutants (POPs) and biometric variables on circulating levels of steroid hormones (androgens, estrogens and progestagens) in male polar bears (Ursus maritimus) from Svalbard, Norway (n = 23). Levels of pregnenolone (PRE), progesterone (PRO), androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2) and 17β-estradiol (βE2) were quantified in polar bear serum by gas chromatography tandem mass spectrometry (GC-MS/MS), while POPs were measured in plasma. Subsequently, associations between hormone concentrations (9 steroids), POPs (21 polychlorinated biphenyls (PCBs), 8 OH-PCBs, 8 organochlorine pesticides (OCPs) and OCP metabolites, and 2 polybrominated diphenyl ethers (PBDEs)) and biological variables (age, head length, body mass, girth, body condition index), capture date, location (latitude and longitude), lipid content and cholesterol levels were examined using principal component analysis (PCA) and orthogonal projections to latent structures (OPLS) modelling. Average concentrations of androgens, estrogens and progestagens were in the range of 0.57-83.7 (0.57-12.4 for subadults, 1.02-83.7 for adults), 0.09-2.69 and 0.57-2.44 nmol/L, respectively. The steroid profiles suggest that sex steroids were mainly synthesized through the Δ-4 pathway in male polar bears. The ratio between androgens and estrogens significantly depended on sexual maturity with androgen/estrogen ratios being approximately 60 times higher in adult males than in subadult males. PCA plots and OPLS models indicated that TS was positively related to biometrics, such as body condition index in male polar bears. A negative relationship was also observed between POPs and DHT. Consequently, POPs and body condition may potentially affect the endocrinological function of steroids, including development of reproductive tissues and sex organs and the

  12. Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome.

    Science.gov (United States)

    Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Abbott, David H

    2005-12-01

    Adrenal androgen excess is found in approximately 25-60% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear. The objective of this study was to determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS. Six prenatally androgenized (PA) and six control female rhesus monkeys of similar age, body weight, and body mass index were studied during d 2-6 of two menstrual cycles or anovulatory 30-d periods. Predexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring one to three cycles after cycle 1, adrenal steroids were determined 14.5-16.0 h after an i.m. injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an i.v. injection of 50 microg ACTH-(1-39). Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. After ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione, and corticosterone but comparable levels of 17alpha-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls. Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable with that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess reprogramming of adrenocortical function.

  13. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    Directory of Open Access Journals (Sweden)

    Abeer M Mahmoud

    Full Text Available Blocking the androgen receptor (AR activity is the main goal of therapies for advanced prostate cancer (PCa. However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  14. Unusual estrogen-binding liver protein: additional data on the structural determinants of androgenic ligands

    International Nuclear Information System (INIS)

    Smirnov, A.N.; Shchelkunova, T.A.; Rozen, V.B.

    1986-01-01

    The relative competitive activity of a number of androstane derivatives was determined according to the 50% displacement of [ 3 H] estradiol from complexes with an unusual estrogen-binding protein (UEBP) of the liver of male rats. It was shown that: (1) the bulk of the energy of the bond of the steroid to protein is due to hydrophobic interactions; (2) the real ability to form specific complexes with the UEBP at androgen concentrations close to the physiological is determined by the 17β-hydroxyl and is enhanced by the 3α- or 2α-hydroxy group; (3) the 3- and 17-keto groups weaken the interaction of androgens with the UEBP; (4) cis-coupling of the A and B rings in the molecule of androgens does not prevent the binding of the steroids to protein. These data substantially refine the concepts of the mechanisms of the interaction of androgens with the UEBP and may promote an elucidation of the physiological function of this protein

  15. Expression of androgen-binding protein (ABP) in human cardiac myocytes.

    Science.gov (United States)

    Schock, H W; Herbert, Z; Sigusch, H; Figulla, H R; Jirikowski, G F; Lotze, U

    2006-04-01

    Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

  16. Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

    Directory of Open Access Journals (Sweden)

    Hiroki Ide

    2015-01-01

    Full Text Available There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.

  17. Urine stability and steroid profile: towards a screening index of urine sample degradation for anti-doping purpose.

    Science.gov (United States)

    Mazzarino, Monica; Abate, Maria Gabriella; Alocci, Roberto; Rossi, Francesca; Stinchelli, Raffaella; Molaioni, Francesco; de la Torre, Xavier; Botrè, Francesco

    2011-01-10

    The presence of microorganisms in urine samples, under favourable conditions of storage and transportation, may alter the concentration of steroid hormones, thus altering the correct evaluation of the urinary steroid profile in doping control analysis. According to the rules of the World Anti-Doping Agency (WADA technical document TD2004 EAAS), a testosterone deconjugation higher than 5% and the presence of 5α-androstane-3,17-dione and 5β-androstane-3,17-dione in the deconjugated fraction, are reliable indicators of urine degradation. The determination of these markers would require an additional quantitative analysis since the steroids screening analysis, in anti-doping laboratories, is performed in the total (free+conjugated) fraction. The aim of this work is therefore to establish reliable threshold values for some representative compounds (namely 5α-androstane-3,17-dione and 5β-androstane-3,17-dione) in the total fraction in order to predict directly at the screening stage the potential microbial degradation of the urine samples. Preliminary evidence on the most suitable degradation indexes has been obtained by measuring the urinary concentration of testosterone, epitestosterone, 5α-androstane-3,17-dione and 5β-androstane-3,17-dione by gas chromatography-mass spectrometric every day for 15 days in the deconjugated, glucuronide and total fraction of 10 pools of urines from 60 healthy subjects, stored under different pH and temperature conditions, and isolating the samples with one or more markers of degradation according to the WADA technical document TD2004EAAS. The threshold values for 5α-androstane-3,17-dione and 5β-androstane-3,17-dione were therefore obtained correlating the testosterone deconjugation rate with the urinary concentrations of 5α-androstane-3,17-dione and 5β-androstane-3,17-dione in the total fraction. The threshold values suggested as indexes of urine degradation in the total fraction were: 10 ng mL(-1) for 5α-androstane-3,17-dione

  18. Radioimmunoassay of anabolic steroids

    International Nuclear Information System (INIS)

    Hampl, R.; Stranska, I.; Starka, L.; Picha, J.; Chundela, B.

    1978-01-01

    Alternative antisera against 17 α-methyltestosterone and 19-nortestosterone were raised and used for radioimmunoassay of anabolic steroids. Tritiated compounds were used as radioligands. The RIA method suitable for doping control is proposed for 17 α-alkylated anabolic steroids in both plasma and urine, using qoat antiserum against methyltestosterone-3-carboxymethyloxime-BSA. Sensitivity of the method was expressed as least amount of nonradioactive methandienone which, when added to normal urine or plasma, caused statistically significant decrease of measured supernatant radioactivity at 99% level. The amounts from 50 to 500 pg were tested, each in eight parallel determinations. The amounts of 100 pg for plasma and 200 pg for urine met these criteria. The respective coefficients of variation did not depend on the amount of steroid added in this range. They averaged 4.60% for plasma and 4.95% for urine, respectively. (T.I.)

  19. Masculinization of Nile tilapia (Oreochromis niloticus) by immersion in androgens

    Science.gov (United States)

    Gale, W.L.; Fitzpatrick, M.S.; Lucero, M.; Contreras-Sanchez, W.M.; Schreck, C. B.

    1999-01-01

    The use of all-male populations increases the efficiency and feasibility of tilapia aquaculture. The objective of this study was to determine the efficacy of a short-term immersion procedure for masculinizing Nile tilapia (Oreochromis niloticus). Two synthetic androgens were evaluated: 17α-methyldihydrotestosterone (MDHT) and 17α-methyltestosterone (MT). Exposure (3 h) on 10 and again on 13 days post-fertilization to MDHT at 500 μg/1 successfully masculinized fry in all experiments, resulting in 100, 94 and 83 ± 2% males in Experiments 1, 2 and 3, respectively. Immersions in MDHT or MT at 100 μg/1 resulted in significantly skewed sex ratios in Experiments 1 and 3 (MT resulted in 73 and 83 ± 3% males; and MDHT resulted in 72 and 91 ± 1% males) but not in Experiment 2. Immersion in MT at 500 μg/1 only caused masculinization in Experiment 3. Although further research and refinement is needed, immersion of Nile tilapia in MDHT may provide a practical alternative to the use of steroid-treated feed. Furthermore, when compared with current techniques for steroid-induced sex inversion of tilapia, short-term immersion reduces the period of time that workers are exposed to anabolic steroids.

  20. Genetics Home Reference: androgen insensitivity syndrome

    Science.gov (United States)

    ... Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this ... characteristics or signs of both male and female sexual development. Complete androgen insensitivity syndrome occurs when the body ...

  1. Male patients with partial androgen insensitivity syndrome

    DEFF Research Database (Denmark)

    Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm

    2012-01-01

    To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome.......To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome....

  2. Influence of testosterone on synaptic transmission in the rat medial vestibular nuclei: estrogenic and androgenic effects.

    Science.gov (United States)

    Grassi, S; Frondaroli, A; Di Mauro, M; Pettorossi, V E

    2010-12-15

    In brainstem slices of young male rat, we investigated the influence of the neuroactive steroid testosterone (T) on the synaptic responses by analyzing the field potential evoked in the medial vestibular nucleus (MVN) by vestibular afferent stimulation. T induced three distinct and independent long-term synaptic changes: fast long-lasting potentiation (fLP), slow long-lasting potentiation (sLP) and long-lasting depression (LD). The fLP was mediated by 17β-estradiol (E(2)) since it was abolished by blocking the estrogen receptors (ERs) or the enzyme converting T to E(2). Conversely, sLP and LD were mediated by 5α-dihydrotestosterone (DHT) since they were prevented by blocking the androgen receptors (ARs) or the enzyme converting T to DHT. Therefore, the synaptic effects of T were mediated by its androgenic or estrogenic metabolites. The pathways leading to estrogenic and androgenic conversion of T might be co-localized since, the occurrence of fLP under block of androgenic pathway, and that of sLP and LD under estrogenic block, were higher than those observed without blocks. In case of co-localization, the effect on synaptic transmission should depend on the prevailing enzymatic activity. We conclude that circulating and neuronal T can remarkably influence synaptic responses of the vestibular neurons in different and opposite ways, depending on its conversion to estrogenic or androgenic metabolites. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Polymorphic variation in the androgen receptor gene: association with risk of testicular germ cell cancer and metastatic disease

    DEFF Research Database (Denmark)

    Västermark, Åke; Giwercman, Yvonne Lundberg; Hagströmer, Oskar

    2011-01-01

    Increasing incidence of testicular germ cell cancer (TGCC) is most probably related to environment and lifestyle. However, an underlying genetic predisposition may play a role and since sex steroids are assumed to be important for the rise and progression of TGCC, a study of androgen receptor (AR...... of endocrine disruptors. From a biological point of view, our findings strengthen the hypothesis of the importance of androgen action in the aetiology and pathogenesis of testicular malignancy. Future studies should focus on the impact of sex hormones on foetal germ cell development and the interaction between...

  4. Mind Over Matter: Anabolic Steroids

    Science.gov (United States)

    ... Download PDF 830.69 KB Anabolic steroids are artificial versions of a hormone that's in all of us—testosterone. Some people take anabolic steroid pills or injections to try to build muscle faster. The Brain's Response to Anabolic Steroids Hi, ...

  5. Selective amine catalysed steroidal dimerization

    Indian Academy of Sciences (India)

    of cholesterol is the formation of a green colour in concentrated sulphuric acid, and this was shown to be due to a polyenyl steroidal dimer carbocation.7–9 Many dimeric and oligomeric steroids exhibit interesting micellular, detergent and liquid crystal behaviour.10,11. Most of the steroidal dimmers are also well-known.

  6. Steroids facing emotions

    NARCIS (Netherlands)

    Putman, P.L.J.

    2006-01-01

    The studies reported in this thesis have been performed to gain a better understanding about motivational mediators of selective attention and memory for emotionally relevant stimuli, and about the roles that some steroid hormones play in regulation of human motivation and emotion. The stimuli used

  7. Radioimmunoassay of steroid hormone

    International Nuclear Information System (INIS)

    Murakami, Tadashi

    1975-01-01

    Low acid pepsin treated gamma-globulin was applied to ammonium sulfate salting out method, which was a method to separate bound fraction from free one in radioimmunoassay of steroid hormone, and the effect of the separation and the standard curve were examined. Pepsin treated gamma-globulin was prepared in pH 1.5 to 5.5 and then the pepsin was completely removed. It had an effect to accelerate the precipitation in radioimmunoassay of steroid hormone labelled with 3 H. The effect of pepsin treated gamma-globulin to adhere free steroid hormone and to slat out bound one was compared with that of human gamma-globulin. Pepsin treated gamma-globulin, which was water soluble, could easier reach its optimal concentration, and the separation effect was better than human gamma-globulin. The standard curve of it was steeper, particularly in a small dose, and the reproducibility was also better. It could be applied not only to aldosterone and DOC, but also to the steroid hormones, such as progesterone and DHEA, and it seemed suitable for routine measurement method. (Kanao, N.)

  8. Androgen and androgen metabolite levels in serum and urine of East African chimpanzees (Pan troglodytes schweinfurthii): comparison of EIA and LC-MS analyses.

    Science.gov (United States)

    Preis, Anna; Mugisha, Lawrence; Hauser, Barbara; Weltring, Anja; Deschner, Tobias

    2011-12-01

    The primary male androgen testosterone (T) is often used as an endocrinological marker to investigate androgen-behaviour interactions in males. In chimpanzees and bonobos, studies investigating the relationship between T levels and dominance rank or aggressive behaviour have revealed contradictory results. The immunoassays used in these studies were originally developed for the measurement of steroids in serum. Their application to non-invasively collected samples, however, can lead to methodological problems due to cross-reacting metabolites, which might occur in urine or faeces but not in blood. The overall aim of this study, therefore, is to clarify whether a T enzyme immunoassay (EIA) is an applicable method to monitor testicular function in adult male chimpanzees. To estimate the impact of cross-reacting androgens on the used T EIA, we compared the results of an EIA measurement with a set of androgen metabolite levels measured by LC-MS. In urine from male chimpanzees, cross-reactivities appear to exist mainly with T and its exclusive metabolites, 5α-dihydrotestosterone (5α-DHT) and 5α-androstanediol (androstanediol). Both urinary and serum T levels of male chimpanzees were significantly higher than female T levels when measured with the T EIA, indicating a reliable measurement of testicular androgens and their exclusive metabolites with the used EIA. In urine from female chimpanzees, the comparison between LC-MS and T EIA results indicated a higher impact of cross-reactions with adrenal androgen metabolites. Therefore, the investigation of urinary T levels in female chimpanzees with a T EIA seems to be problematic. Overall our results show that a T EIA can be a reliable method to monitor testicular function in male chimpanzee urine and that LC-MS is a valuable tool for the validation of immunoassays. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Anabolic Steroids...What's the Hype?...

    Science.gov (United States)

    Landry, Gregory L.; Wagner, Lauris L.

    This pamphlet uses a question-and-answer format to examine the use and abuse of anabolic steroids. It begins by explaining that all steroids are not anabolic steroids and that anabolic steroids are those used specifically to build muscles quickly. Medical uses of anabolic steroids are reviewed; how people get steroids, how they take them, and…

  10. Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet α/β cell ratio and subsequent insulin secretion.

    Science.gov (United States)

    Ramaswamy, S; Grace, C; Mattei, A A; Siemienowicz, K; Brownlee, W; MacCallum, J; McNeilly, A S; Duncan, W C; Rae, M T

    2016-06-06

    Exogenous androgenic steroids applied to pregnant sheep programmes a PCOS-like phenotype in female offspring. Via ultrasound guidance we applied steroids directly to ovine fetuses at d62 and d82 of gestation, and examined fetal (day 90 gestation) and postnatal (11 months old) pancreatic structure and function. Of three classes of steroid agonists applied (androgen - Testosterone propionate (TP), estrogen - Diethystilbesterol (DES) and glucocorticoid - Dexamethasone (DEX)), only androgens (TP) caused altered pancreatic development. Beta cell numbers were significantly elevated in prenatally androgenised female fetuses (P = 0.03) (to approximately the higher numbers found in male fetuses), whereas alpha cell counts were unaffected, precipitating decreased alpha:beta cell ratios in the developing fetal pancreas (P = 0.001), sustained into adolescence (P = 0.0004). In adolescence basal insulin secretion was significantly higher in female offspring from androgen-excess pregnancies (P = 0.045), and an exaggerated, hyperinsulinaemic response to glucose challenge (P = 0.0007) observed, whereas prenatal DES or DEX treatment had no effects upon insulin secretion. Postnatal insulin secretion correlated with beta cell numbers (P = 0.03). We conclude that the pancreas is a primary locus of androgenic stimulation during development, giving rise to postnatal offspring whose pancreas secreted excess insulin due to excess beta cells in the presence of a normal number of alpha cells.

  11. Hormonally-mediated Epigenetic Changes to Steroid Receptors in the Developing Brain: Implications for Sexual Differentiation

    OpenAIRE

    Nugent, Bridget M.; Schwarz, Jaclyn M.; McCarthy, Margaret M.

    2010-01-01

    The establishment of sex-specific neural morphology, which underlies sex-specific behaviors, occurs during a perinatal sensitive window in which brief exposure to gonadal steroid hormones produces permanent masculinization of the brain. In the rodent, estradiol derived from testicular androgens is a principle organizational hormone. The mechanism by which transient estradiol exposure induces permanent differences in neuronal anatomy has been widely investigated, but remains elusive. Epigeneti...

  12. CLONING AND IN VITRO EXPRESSION AND CHARACTERIZATION OF THE ANDROGEN RECEPTOR AND ISOLATION OF ESTROGEN RECEPTOR α FROM THE FATHEAD MINNOW (PIMEPHALES PROMELAS)

    Science.gov (United States)

    In vitro screening assays designed to identify hormone mimics or antagonists typically use mammalian (rat, human) estrogen (ER) and androgen receptors (AR). Although we know that the amino acid sequences of steroid receptors in nonmammalian vertebrates are not identical to the ma...

  13. Establishment of a novel immortalized human prostatic epithelial cell line stably expressing androgen receptor and its application for the functional screening of androgen receptor modulators

    International Nuclear Information System (INIS)

    Yu, Shan; Wang, Ming-Wei; Yao, Xiaoqiang; Chan, F.L.

    2009-01-01

    In this study, we developed a human prostatic epithelial cell line BPH-1-AR stably expressing AR by lentiviral transduction. Characterization by immunoblot and RT-PCR showed that AR was stably expressed in all representative BPH-1-AR clones. Androgen treatment induced a secretory differentiation phenotype in BPH-1-AR cells but suppressed their cell proliferation. Treatments with AR agonists induced transactivation of a transfected PSA-gene promoter reporter in BPH-1-AR cells, whereas this transactivation was suppressed by an AR antagonist flutamide, indicating that the transduced AR in BPH-1-AR cells was functional. Finally, we utilized BPH-1-AR cells to evaluate the androgenic activities and growth effects of five newly developed non-steroidal compounds. Results showed that these compounds showed androgenic activities and growth-inhibitory effects on BPH-1-AR cells. Our results showed that BPH-1-AR cell line would be a valuable in vitro model for the study of androgen-regulated processes in prostatic epithelial cells and identification of compounds with AR-modulating activities.

  14. High abundance androgen receptor in goldfish brain: characteristics and seasonal changes

    International Nuclear Information System (INIS)

    Pasmanik, M.; Callard, G.V.

    1988-01-01

    Testosterone (T) exerts its actions in brain directly via androgen receptors or, after aromatization to estradiol, via estrogen receptors. Brain aromatase activity in teleost fish is 100-1000 times greater than in mammals and would be expected to significantly reduce the quantity of androgen available for receptor binding. Experiments were carried out on the goldfish Carassius auratus to determine if androgen receptors are present in teleost brain and whether their physicochemical properties reflect elevated aromatase. Cytosolic and nuclear extracts were assayed with the use of [ 3 H]T and charcoal, Sephadex LH-20, or DNA-cellulose chromatography to separate bound and free steroids. Binding activity was saturable and had an equally high affinity for T and 5 alpha-dihydrotestosterone. Although mibolerone was a relatively weak competitor, the putative teleost androgen 11-ketotestosterone, methyltrienolone (R1881), estradiol, progesterone, and cortisol were poor ligands. Characteristics that distinguish this receptor from a steroid-binding protein in goldfish serum are the presence of binding activity in both nuclear and cytosolic extracts, a low rate of ligand-receptor dissociation, electrophoretic mobility, sedimentation properties in low vs. high salt, and tissue distribution. DNA cellulose-adhering and nonadhering forms were detected, but these did not differ in other variables measured. Although goldfish androgen receptors resembled those of mammals in all important physicochemical characteristics, they were unusually abundant compared to levels in rat brain, but comparable to levels in prostate and other male sex hormone target organs. Moreover, there were seasonal variations in total receptors, with a peak at spawning (April) 4- to 5-fold higher than values in reproductively inactive fish

  15. [Ingestion of anabolic steroids and ischaemic stroke. A clinical case report and review of the literature].

    Science.gov (United States)

    García-Esperón, Carlos; Hervás-García, José Vicente; Jiménez-González, Marta; Pérez de la Ossa-Herrero, Natalia; Gomis-Cortina, Meritxell; Dorado-Bouix, Laura; López-Cancio Martinez, Elena; Castaño-Duque, Carlos H; Millán-Torné, Mónica; Dávalos, Antonio

    2013-03-16

    INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers.

  16. Src Kinase Dependent Rapid Non-genomic Modulation of Hippocampal Spinogenesis Induced by Androgen and Estrogen

    Directory of Open Access Journals (Sweden)

    Mika Soma

    2018-05-01

    Full Text Available Dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from an axon terminal at the synapse. Memories are stored in synapses which consist of spines and presynapses. Rapid modulations of dendritic spines induced by hippocampal sex steroids, including dihydrotestosterone (DHT, testosterone (T, and estradiol (E2, are essential for synaptic plasticity. Molecular mechanisms underlying the rapid non-genomic modulation through synaptic receptors of androgen (AR and estrogen (ER as well as its downstream kinase signaling, however, have not been well understood. We investigated the possible involvement of Src tyrosine kinase in rapid changes of dendritic spines in response to androgen and estrogen, including DHT, T, and E2, using hippocampal slices from adult male rats. We found that the treatments with DHT (10 nM, T (10 nM, and E2 (1 nM increased the total density of spines by ~1.22 to 1.26-fold within 2 h using super resolution confocal imaging of Lucifer Yellow-injected CA1 pyramidal neurons. We examined also morphological changes of spines in order to clarify differences between three sex steroids. From spine head diameter analysis, DHT increased middle- and large-head spines, whereas T increased small- and middle-head spines, and E2 increased small-head spines. Upon application of Src tyrosine kinase inhibitor, the spine increases induced through DHT, T, and E2 treatments were completely blocked. These results imply that Src kinase is essentially involved in sex steroid-induced non-genomic modulation of the spine density and morphology. These results also suggest that rapid effects of exogenously applied androgen and estrogen can occur in steroid-depleted conditions, including “acute” hippocampal slices and the hippocampus of gonadectomized animals.

  17. Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss.

    Science.gov (United States)

    Reinehr, Thomas; Kulle, Alexandra; Rothermel, Juliane; Knop-Schmenn, Caroline; Lass, Nina; Bosse, Christina; Holterhus, Paul-Martin

    2017-05-01

    The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC-MS/MS steroid profiling at baseline and one year later. At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS. © 2017 The authors.

  18. Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss

    Directory of Open Access Journals (Sweden)

    Thomas Reinehr

    2017-05-01

    Full Text Available Objective: The underlying mechanisms of polycystic ovarian syndrome (PCOS are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. Design: This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13–16 years (50% with PCOS participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. Methods: We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S, estrone and estradiol by LC–MS/MS steroid profiling at baseline and one year later. Results: At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. Conclusions: The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS.

  19. Steroid receptor profiling of vinclozolin and its primary metabolites

    International Nuclear Information System (INIS)

    Molina-Molina, Jose-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernandez, Mariana-Fatima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolas; Balaguer, Patrick

    2006-01-01

    Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERα and ERβ). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR >> PR > GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERβ. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process

  20. Steroid receptor profiling of vinclozolin and its primary metabolites.

    Science.gov (United States)

    Molina-Molina, José-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernández, Mariana-Fátima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolás; Balaguer, Patrick

    2006-10-01

    Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERalpha and ERbeta). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR>PR>GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.

  1. Radioimmunoassay of synthetic steroids

    Energy Technology Data Exchange (ETDEWEB)

    Raynaud, J -P; Bucourt, R; Salmon, J

    1975-12-01

    The sensitivity of a radioimmunoassay depends on the intrinsic association constant of the interaction between ligand and antibody. Its specificity depends on the position of the chain which forms the link with the antigen. Thus, an antibody specific of estradiol has been obtained by coupling estradiol to albumin via a chain at position 7. For synthetic steroids the structure of which is sufficiency different from that of natural hormones, the requirements for a sensitive assay method not involving chromatography are simply maximum affinity and positioning of the couple at a site which does not undergo metabolic attack. These criteria were used to develop assays for R 2858 and R 2453 which obviate the need to administer radioactive product in clinical pharmacology. Cross-reaction with structural analogs may be used to assay competitors. Thus, R 2323 antibody, highly specific for endogenous steroids, may be used to assay other trienes such as R 1697 (trenbolone) and R 2010 (norgestrienone).

  2. Steroid receptor expression in the fish inner earvaries with sex, social status, and reproductive state

    Directory of Open Access Journals (Sweden)

    Fernald Russell D

    2010-04-01

    Full Text Available Abstract Background Gonadal and stress-related steroid hormones are known to influence auditory function across vertebrates but the cellular and molecular mechanisms responsible for steroid-mediated auditory plasticity at the level of the inner ear remain unknown. The presence of steroid receptors in the ear suggests a direct pathway for hormones to act on the peripheral auditory system, but little is known about which receptors are expressed in the ear or whether their expression levels change with internal physiological state or external social cues. We used qRT-PCR to measure mRNA expression levels of multiple steroid receptor subtypes (estrogen receptors: ERα, ERβa, ERβb; androgen receptors: ARα, ARβ; corticosteroid receptors: GR2, GR1a/b, MR and aromatase in the main hearing organ of the inner ear (saccule in the highly social African cichlid fish Astatotilapia burtoni, and tested whether these receptor levels were correlated with circulating steroid concentrations. Results We show that multiple steroid receptor subtypes are expressed within the main hearing organ of a single vertebrate species, and that expression levels differ between the sexes. We also show that steroid receptor subtype-specific changes in mRNA expression are associated with reproductive phase in females and social status in males. Sex-steroid receptor mRNA levels were negatively correlated with circulating estradiol and androgens in both males and females, suggesting possible ligand down-regulation of receptors in the inner ear. In contrast, saccular changes in corticosteroid receptor mRNA levels were not related to serum cortisol levels. Circulating steroid levels and receptor subtype mRNA levels were not as tightly correlated in males as compared to females, suggesting different regulatory mechanisms between sexes. Conclusions This is the most comprehensive study of sex-, social-, and reproductive-related steroid receptor mRNA expression in the peripheral

  3. Androgen excess: Investigations and management.

    Science.gov (United States)

    Lizneva, Daria; Gavrilova-Jordan, Larisa; Walker, Walidah; Azziz, Ricardo

    2016-11-01

    Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response. Copyright © 2016. Published by Elsevier Ltd.

  4. Anabolic steroids and head injury.

    Science.gov (United States)

    Mills, James D; Bailes, Julian E; Turner, Ryan C; Dodson, Sean C; Sakai, Jun; Maroon, Joseph C

    2012-01-01

    The suggestion has been made that neurological changes seen in the syndrome of chronic traumatic encephalopathy may be due to exogenous anabolic steroid use rather than traumatic brain injury. To determine whether administration of anabolic steroids alters the pathophysiology of traumatic brain injury. Sixty adult male Sprague-Dawley rats and a linear acceleration model of traumatic brain injury were used. Experimental groups were (1) preinjury anabolic steroids, (2) preinjury placebo carrier, (3) anabolic steroids without injury, (4) no steroids and no injury, (5) postinjury placebo carrier, and (6) postinjury anabolic steroids. Following a 30-day recovery, rats were euthanized, and brainstem white matter tracts underwent fluorescent immunohistochemical processing and labeling of β-amyloid precursor protein (APP), a marker of axonal injury. Digital imaging and statistical analyses were used to determine whether anabolic steroid administration resulted in a significant change in the number of injured axons. There was no statistically significant difference in number of APP-positive axons by immunohistochemical analysis between respective anabolic steroid and placebo groups. Using a standard acceleration-deceleration model of mild traumatic brain injury, we have shown successful visualization of traumatically injured axons with antibody staining of APP. Our results indicate no statistically significant effect of anabolic steroids on the number of APP-positive axons. With the use of this model, and within its limitations, we see no adverse effect or causative role of anabolic steroid administration on the brain following mild traumatic brain injury using APP counts as a marker for anatomic injury.

  5. Immunocharacteristics of oestrogen and androgen target cells in the anterior pituitary gland of the chick as embryo demonstrated by a combined method of autoradiography and immunohistochemistry

    International Nuclear Information System (INIS)

    Gasc, J.-M.; Sar, M.; Stumpf, W.E.

    1980-01-01

    The distribution of oestrogen and androgen target cells in the anterior pituitary gland of the chick embryo on days 10, 12 and 15 of incubation was studied 1 h after the injection of tritium-labelled steroid hormone using the thaw-mount autoradiographic technique. Oestradiol target cells were localized in the caudal zone that corresponds to the so-called 'caudal lobe', while androgen target cells were found throughout the rostral and caudal lobes of the anterior gland. With a combined autoradiography and immunohistochemistry technique, most of the oestrogen target cells showed immunoreactivity to turkey LH antiserum but not to adrenocorticotrophin (1-24) and β-thyrotrophin antisera. In contrast, androgen target cells did not show positive immunoreactivity to the three antisera used. The results suggested a direct and early involvement of oestrogens but not of androgens in the feedback regulation of pituitary gonadotrophin secretion in the chick embryo. (U.K.)

  6. Sarcopenia and androgens: A link between pathology and treatment

    Directory of Open Access Journals (Sweden)

    Carla eBasualto-Alarcón

    2014-12-01

    Full Text Available Sarcopenia, the age-related loss of skeletal muscle mass and function, is becoming more prevalent as the lifespan continues to increase in most populations. As sarcopenia is highly disabling, being associated with increased risk of dependence, falls, fractures, weakness, disability, and death, development of approaches to its prevention and treatment are required. Androgens are the main physiologic anabolic steroid hormones and normal testosterone levels are necessary for a range of developmental and biological processes, including maintenance of muscle mass. Testosterone concentrations decline as age increase, suggesting that low plasma testosterone levels can cause or accelerate muscle- and age-related diseases, as sarcopenia. Currently, there is increasing interest on the anabolic properties of testosterone for therapeutic use in muscle diseases including sarcopenia. However, the pathophysiological mechanisms underlying this muscle syndrome and its relationship with plasma level of androgens are not completely understood. This review discusses the recent findings regarding sarcopenia, the intrinsic and extrinsic mechanisms involved in the onset and progression of this disease and the treatment approaches that have been developed based on testosterone deficiency and their implications.

  7. Serum-sex steroids, gonadotrophins and sex hormone-binding globulin inprostatic hyperplasia

    International Nuclear Information System (INIS)

    Ansari, Mohammad A. Jalil; Begum, D.; Islam, F.

    2008-01-01

    Benign prostatic hyperplasia (BPH) develops in elderly males when serumandrogens are relatively lower than in healthy younger males, but is not wellunderstood whether and how sex steroids are altered in prostatic hyperplasia.It is also uncertain that whether there is any change in sex steroids levelsin males older than 40 years of age. The use of androgens in elderly males isoften discouraged because of the probable worsening effect of androgens onprostatism. This study aimed to determine the relationship between prostatichyperplasia and sex steroid levels and whether there is any significantchange in these hormones after the age of 40 years. We studied healthy malesof >40 years with (n=92) or without (n=93) clinical prostatic hyperplasia.Serum testosterone, estradiol, gonadotrophins and sex hormone-bindingglobulin (SHBG) were compared. The hormones and SHGB were also correlatedwith age. No significant difference was found in any hormone in cases withprostatic hyperplasia as compared with the controls. There was no significantage-related change in any hormone except estradiol where as a negativecorrelation (P<0.003) with age was found. Serum sex steroids and SHGBremained unchanged in symptomatic prostatic hyperplasia and except forestrdoil there was no significant age-related change in serum testosterone,gonadotrophins and SHGB in healthy males after the fourth decade. Morestudies are needed to confirm the age-related decline of estrogens in males.(author)

  8. Oral contraceptives and neuroactive steroids.

    Science.gov (United States)

    Rapkin, Andrea J; Biggio, Giovanni; Concas, Alessandra

    2006-08-01

    A deregulation in the peripheral and brain concentrations of neuroactive steroids has been found in certain pathological conditions characterized by emotional or affective disturbances, including major depression and anxiety disorders. In this article we summarize data pertaining to the modulatory effects of oral contraceptive treatment on neuroactive steroids in women and rats. Given that the neuroactive steroids concentrations are reduced by oral contraceptives, together with the evidence that a subset of women taking oral contraceptives experience negative mood symptoms, we propose the use of this pharmacological treatment as a putative model to study the role of neuroactive steroids in the etiopathology of mood disorders. Moreover, since neuroactive steroids are potent modulators of GABA(A) receptor function and plasticity, the treatment with oral contraceptives might also represent a useful experimental model to further investigate the physiological role of these steroids in the modulation of GABAergic transmission.

  9. Effect of the systemic versus inhalatory administration of synthetic glucocorticoids on the urinary steroid profile as studied by gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Mazzarino, Monica; Rossi, Francesca; Giacomelli, Laura; Botre, Francesco

    2006-01-01

    This paper presents a gas chromatography-mass spectrometry (GC-MS) study carried out on human urine to verify whether the administration of glucocorticoids can affect the urinary steroid profile, and especially the levels of endogenous glucocorticoids, androgens and their main metabolites. Betamethasone and beclomethasone, administered either systemically (per os or i.m.) or locally (by inhalation) have been studied. The determination of the urinary levels of endogenous glucocorticoids and androgens was carried out by GC-MS in electron impact ionization mode. Data were evaluated taking into account the baseline individual variability, and compared with values obtained on a control group. Detectable differences were recorded in the steroids metabolites excretion profiles between men and women. The circadian variability of the steroid profile was the same for both sexes, showing a maximum during the morning hours. After systemic treatment with synthetic glucocorticoids, the relative urinary concentrations of corticosteroids, androgens and of their metabolites were significantly altered, recording a transient decrease of the concentration of cortisol and tetrahydrocortisol and a parallel, although less pronounced, increase of the concentration of testosterone, epitestosterone and related androgenic steroids; while no effects were recorded if the administration was by inhalation

  10. His Biceps become Him: A Test of Objectification Theory's Application to Drive for Muscularity and Propensity for Steroid Use in College Men

    Science.gov (United States)

    Parent, Mike C.; Moradi, Bonnie

    2011-01-01

    Men's body image problems may manifest as an unhealthy drive for muscularity and propensity to use anabolic-androgenic steroids (AAS). Aspects of objectification theory were integrated with literature on men's drive for muscularity and AAS use to identify correlates of these problems. The resultant model was tested with path analyses of data from…

  11. Effect of the systemic versus inhalatory administration of synthetic glucocorticoids on the urinary steroid profile as studied by gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Mazzarino, Monica [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Rossi, Francesca [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Giacomelli, Laura [Dipartimento di Scienze Chirurgiche, Universita La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Botre, Francesco [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy) and Dipartimento CGMIA, Universita La Sapienza, Via del Castro Laurenziano 9, 00161 Rome (Italy)]. E-mail: francesco.botre@uniroma1.it

    2006-02-10

    This paper presents a gas chromatography-mass spectrometry (GC-MS) study carried out on human urine to verify whether the administration of glucocorticoids can affect the urinary steroid profile, and especially the levels of endogenous glucocorticoids, androgens and their main metabolites. Betamethasone and beclomethasone, administered either systemically (per os or i.m.) or locally (by inhalation) have been studied. The determination of the urinary levels of endogenous glucocorticoids and androgens was carried out by GC-MS in electron impact ionization mode. Data were evaluated taking into account the baseline individual variability, and compared with values obtained on a control group. Detectable differences were recorded in the steroids metabolites excretion profiles between men and women. The circadian variability of the steroid profile was the same for both sexes, showing a maximum during the morning hours. After systemic treatment with synthetic glucocorticoids, the relative urinary concentrations of corticosteroids, androgens and of their metabolites were significantly altered, recording a transient decrease of the concentration of cortisol and tetrahydrocortisol and a parallel, although less pronounced, increase of the concentration of testosterone, epitestosterone and related androgenic steroids; while no effects were recorded if the administration was by inhalation.

  12. Collision Cross Section (CCS) Database: An Additional Measure to Characterize Steroids.

    Science.gov (United States)

    Hernández-Mesa, Maykel; Le Bizec, Bruno; Monteau, Fabrice; García-Campaña, Ana M; Dervilly-Pinel, Gaud

    2018-04-03

    Ion mobility spectrometry enhances the performance characteristics of liquid chromatography-mass spectrometry workflows intended to steroid profiling by providing a new separation dimension and a novel characterization parameter, the so-called collision cross section (CCS). This work proposes the first CCS database for 300 steroids (i.e., endogenous, including phase I and phase II metabolites, and exogenous synthetic compounds), which involves 1080 ions and covers the CCS of 127 androgens, 84 estrogens, 50 corticosteroids, and 39 progestagens. This large database provides information related to all the ionized species identified for each steroid in positive electrospray ionization mode as well as for estrogens in negative ionization mode. CCS values have been measured using nitrogen as drift gas in the ion mobility cell. Generally, direct correlation exists between mass-to-charge ratio ( m/ z) and CCS because both are related parameters. However, several steroids mainly steroid glucuronides and steroid esters have been characterized as more compact or elongated molecules than expected. In such cases, CCS results in additional relevant information to retention time and mass spectral data for the identification of steroids. Moreover, several isomeric steroid pairs (e.g., 5β-androstane-3,17-dione and 5α-androstane-3,17-dione) have been separated based on their CCS differences. These results indicate that adding the CCS to databases in analytical workflows increases selectivity, thus improving the confidence in steroids analysis. Consequences in terms of identification and quantification are discussed. Quality criteria and a construction of an interlaboratory reproducibility approach are also reported for the obtained CCS values. The CCS database described here is made publicly available.

  13. The Sturm und Drang of anabolic steroid use: angst, anxiety, and aggression

    Science.gov (United States)

    Oberlander, Joseph G.; Henderson, Leslie P.

    2014-01-01

    Anabolic androgenic steroids (AAS) are illicitly administered to enhance athletic performance and body image. Although conferring positive actions on performance, steroid abuse is associated with changes in anxiety and aggression. AAS users are often keenly invested in understanding the biological actions of these drugs. Thus, mechanistic information on AAS actions is important not only for the biomedical community, but also for steroid users. Here we review findings from animal studies on the impact of AAS exposure on neural systems that are crucial for the production of anxiety and aggression, and compare the effects of the different classes of AAS and their potential signaling mechanisms, as well as context-, age- and sex-dependent aspects of their actions. PMID:22516619

  14. Metabolism of anabolic steroids and their relevance to drug detection in horseracing.

    Science.gov (United States)

    Teale, Philip; Houghton, Edward

    2010-06-01

    The fight against doping in sport using analytical chemistry is a mature area with a history of approximately 100 years in horseracing. In common with human sport, anabolic/androgenic steroids (AASs) are an important group of potential doping agents. Particular issues with their detection are extensive metabolism including both phase I and phase II. A number of the common AASs are also endogenous to the equine. A further issue is the large number of synthetic steroids produced as pharmaceutical products or as 'designer' drugs intended to avoid detection or for the human supplement market. An understanding of the metabolism of AASs is vital to the development of effective detection methods for equine sport. The aim of this paper is to review current knowledge of the metabolism of appropriate steroids, the current approaches to their detection in equine sport and future trends that may affect equine dope testing.

  15. Sex steroids and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Carolyn A Allan

    2014-04-01

    Full Text Available Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

  16. Multiple steroid radioimmunoassays and automation. Versatile techniques for reproductive endocrinology

    International Nuclear Information System (INIS)

    Vihko, R.; Hammond, G.L.; Pakarinen, A.; Viinikka, L.

    1978-01-01

    The combination of the efficient steroid-separating properties of a lipophilic Sephadex derivative Lipidex-5000sup(TM) and the use of antibodies with carefully selected specificity allows the quantitative determination of pregnenolone, progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, 5α-dihydrotestosterone, 5α-androstanedione, androsterone and 5α-androstane-3α, 17β-diol in 1- to 2-ml samples of both blood serum and amniotic fluid as well as in 300- to 600-mg pieces of prostatic tissue. The adaptation of the pipetting unit and incubator of a discrete clinical chemical analyser, System Olli 3000, for the automation of the radioimmunoassays has resulted in a greatly increased through-put and has decreased the experimental error of the procedure. In studies on reproductive endocrinology, the methodology developed has allowed the detection of a sex difference in androgen composition of the amniotic fluid early in pregnancy. Further, it is very likely that the decline in steroid production by the testis seen during the first year of life and then in senescence is affected by basically different mechanisms. There are also important differences in the steroid content of normal, hyperplastic and carcinomatous prostate. (author)

  17. Multiple steroid radioimmunoassays and automation: versatile techniques for reproductive endocrinology

    International Nuclear Information System (INIS)

    Vihko, R.; Hammond, G.L.; Pakarinen, A.; Viinikka, L.

    1977-01-01

    The combination of the efficient steroid separating properties of a lipophilic Sephadex derivative Lipidex-5000sup(TM), with the use of antibodies with carefully selected specificity allows the quantitative determination of pregnenolone, progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, 5α-dihydrotestosterone, 5α-androstanedione, androsterone and 5α-androstane-3α, 17β-diol from 1-2 ml samples of blood serum, amniotic fluid or 300-600 mg pieces of prostatic tissue. The adaptation of the pipetting unit and incubator of a discrete clinical chemical analyzer, System Olli 3000, for the automation of the radioimmunoassays has resulted in a greatly increased through-put and decreased experimental error of the procedure. In studies on reproductive endocrinology, the methodology developed has allowed the detection of a sex difference in androgen composition of the amniotic fluid early in pregnancy. Further, it is very likely that the decline in steroid production by the testis seen during the first year of life and then in senescence is affected by basically different mechanisms. There are also important differences in the steroid content of normal, hyperplastic and carcinomatous prostate. (orig.) [de

  18. Steroid metabolism in pregnant hamster. I

    International Nuclear Information System (INIS)

    Marchut, M.

    1980-01-01

    Quartered placentae from 12- and 15-day pregnant hamsters were incubated with 14 C labelled pregnenolone and progesterone and the products of their conversion were identified by chromatographic and isotope dilution methods. Pregnenolone was converted to progesterone, 7α-hydroxypregnenolone, 7α-hydroxyprogesterone, 3α-hydroxy-5β-pregnan-20-one, 3β-hydroxy-5α-pregnan-20-one, 3α-hydroxy-5α-pregnan-20-one, 5β-pregnane-3,20-dione and 5α-pregnane-3,20-dione. Except for 7α-hydroxypregnenolone, the same metabolites were identified in the incubates of the placental tissue with progesterone. Thus, the activity of Δ 5 -3β-hydroxysteroid dehydrogenase and Δsup(5→4) isomerase, 7α-hydrΔ 4 -5β- and Δ 4 -5α-reductase enzyme systems was shown in the hamster placenta. The formation of androgens from pregnenolone, progesterone and their 17-hydroxy-derivatives was not observed. There was also no evidence of the formation of estrogens from the above C-21 steroid precursors. (author)

  19. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Martin Ligr

    Full Text Available Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR and estrogen receptor (ER in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.

  20. Integration of ligand and structure-based virtual screening for identification of leading anabolic steroids.

    Science.gov (United States)

    Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; García-de la Vega, José Manuel; Bencomo-Martínez, Alberto; Pupo, Amaury; Agramonte-Delgado, Alina; Marrero-Ponce, Yovani; Ruiz-García, José Alberto; Mikosch, Hans

    2013-11-01

    Parallel ligand- and structure-based virtual screenings of 269 steroids with anabolic activity evaluated in vivo were performed. The quantitative structure-activity relationship (QSAR) model expressed by selected descriptors as the octanol-water partition coefficient, the molar volume and the quantum mechanical calculated charge values on atoms C1, C2, C5, C9, C10, C14 and C17 of the steroid skeleton, expresses structural features of anabolic steroids (AS) contributing to the transport and steroid-receptor interaction. On the other hand, computational simulations of a candidate ligand binding to a receptor study (a "docking" procedure) predict the association of these AS with the human androgen receptor (AR). Fourteen compounds were identified as lead; the most potent was the 7α-methylestr-4-en-3, 17-dione. It was concluded that a good anabolic activity requires hydrogen bonding interactions between both Arg752 and Gln711 residues in the cycles A with O3 atom of the steroid and either Asn705 and Thr877 residues in the cycles D of steroid with O17 atom. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Androgens and the ageing male

    DEFF Research Database (Denmark)

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men...... 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do...... not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove beneficial...

  2. Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies

    Science.gov (United States)

    Bhasin, Shalender; Jasuja, Ravi

    2010-01-01

    Purpose of review The last decade has witnessed unprecedented discovery effort to develop selective androgen receptor modulators (SARMs) that improve physical function and bone health without adversely affecting the prostate and cardiovascular outcomes. This review describes the historical evolution, the rationale for SARM development, and the mechanisms of testosterone action and SARM selectivity. Recent Findings While steroidal SARMs have been around since the 1940s, a number of nonsteroidal SARMs that do not serve as substrates for CYP19 aromatase or 5α-reductase, act as full agonists in muscle and bone and as partial agonists in prostate are in development. The differing interactions of steroidal and nonsteroidal compounds with AR contribute to their unique pharmacologic actions. Ligand binding induces specific conformational changes in the ligand binding domain, which could modulate surface topology and protein-protein interactions between AR and coregulators, resulting in tissue-specific gene regulation. Preclinical studies have demonstrated the ability of SARMs to increase muscle and bone mass in preclinical rodent models with varying degree of prostate sparing. Phase I trials of SARMs in humans have reported modest increments in fat-free mass. Summary SARMs hold promise as a new class of function promoting anabolic therapies for a number of clinical indications, including functional limitations associated with aging and chronic disease, frailty, cancer cachexia, and osteoporosis. PMID:19357508

  3. Towards an understanding of the evolution of the chorioallantoic placenta: steroid biosynthesis and steroid hormone signaling in the chorioallantoic membrane of an oviparous reptile.

    Science.gov (United States)

    Cruze, Lori; Kohno, Satomi; McCoy, Michael W; Guillette, Louis J

    2012-09-01

    Amniotes, mammals, reptiles, and birds form common extraembryonic membranes during development to perform essential functions, such as protection, nutrient transfer, gas exchange, and waste removal. Together with the maternal uterus, extraembryonic membranes of viviparous (live-bearing) amniotes develop as an endocrine placenta that synthesizes and responds to steroid hormones critical for development. The ability of these membranes to synthesize and respond to steroid hormone signaling has traditionally been considered an innovation of placental amniotes. However, our laboratory recently demonstrated that this ability extends to the chorioallantoic membrane (CAM) of an oviparous (egg-laying) amniote, the domestic chicken, and we hypothesized that steroidogenic extraembryonic membranes could be an evolutionarily conserved characteristic of all amniotes because of similarities in basic structure, function, and shared evolutionary ancestry. In this study, we examined steroid hormone synthesis and signaling in the CAM of another oviparous amniote, the American alligator (Alligator mississippiensis). We quantified mRNA expression of a steroidogenic factor involved in the regulation of steroidogenesis (NR5A1), the key steroidogenic enzymes involved in the synthesis of progestins (HSD3B1), androgens (CYP17A1), and estrogens (CYP19A1), and the receptors involved in the signaling of progestins (PR), androgens (AR), estrogens (ESR1 and ESR2), and glucocorticoids (GR). Furthermore, we performed protein immunolocalization for PR and ESR1. Collectively, our findings indicate that the alligator CAM has the capability to regulate, synthesize, and respond to steroid hormone signaling, thus, supporting our hypothesis that the extraembryonic membranes of Amniota share a unifying characteristic, that is, the ability to synthesize and respond to steroid hormones.

  4. Steroids and Autoimmunity.

    Science.gov (United States)

    Trombetta, Amelia Chiara; Meroni, Marianna; Cutolo, Maurizio

    2017-01-01

    From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs. © 2017 S. Karger AG, Basel.

  5. Steroidal saponins from Sansevieria trifasciata.

    Science.gov (United States)

    Mimaki, Y; Inoue, T; Kuroda, M; Sashida, Y

    1996-12-01

    The methanol extract of the whole plant of Sansevieria trifasciata has yielded 12 steroidal saponins, 10 of which are new constituents. The respective structures of the new compounds have been shown by the spectroscopic evidence, and alkaline- and acid-catalysed degradation. This is the first report of the isolation of steroidal saponins from S. trifasciata.

  6. Challenges in clinical and laboratory diagnosis of androgen insensitivity syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Silva Daniela M

    2011-09-01

    Full Text Available Abstract Introduction Androgen is a generic term usually applied to describe a group of sex steroid hormones. Androgens are responsible for male sex differentiation during embryogenesis at the sixth or seventh week of gestation, triggering the development of the testes and penis in male fetuses, and are directed by the testicular determining factor: the gene SRY (sex determining region on Y chromosome located on the short arm of chromosome Y. The differentiation of male external genitalia (penis, scrotum and penile urethra occurs between the 9th and 13th weeks of pregnancy and requires adequate concentration of testosterone and the conversion of this to another more potent androgen, dihydrotestosterone, through the action of 5α-reductase in target tissues. Case presentation This report describes the case of a teenage girl presenting with a male karyotype, and aims to determine the extension of the mutation that affected the AR gene. A Caucasian girl aged 15 was referred to our laboratory for genetic testing due to primary amenorrhea. Physical examination, karyotype testing and molecular analysis of the androgen receptor were critical in making the correct diagnosis of complete androgen insensitivity syndrome. Conclusions Sex determination and differentiation depend on a cascade of events that begins with the establishment of chromosomal sex at fertilization and ends with sexual maturation at puberty, subsequently leading to fertility. Mutations affecting the AR gene may cause either complete or partial androgen insensitivity syndrome. The case reported here is consistent with complete androgen insensitivity syndrome, misdiagnosed at birth, and consequently our patient was raised both socially and educationally as a female. It is critical that health care providers understand the importance of properly diagnosing a newborn manifesting ambiguous genitalia. Furthermore, a child with a pseudohermaphrodite phenotype should always undergo adequate

  7. Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats.

    Science.gov (United States)

    Oti, Takumi; Takanami, Keiko; Ito, Saya; Ueda, Takashi; Matsuda, Ken Ichi; Kawata, Mitsuhiro; Soh, Jintetsu; Ukimura, Osamu; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2018-04-01

    The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord controls male sexual function in rats. In contrast, in female rats, GRP neurons could scarcely be detected around puberty when circulating ovarian steroid hormones such as estradiol and progesterone levels are increasing. However, little information is available on feminizing or demasculinizing effects of ovarian steroids on the central nervous system in female puberty and adulthood. In this study, to visualize the spinal GRP neurons in vivo, we generated a GRP-promoter-Venus transgenic (Tg) rat line and studied the effects of the sex steroid hormones on GRP expression in the rat lumbar cord by examining the Venus fluorescence. In these Tg rats, the sexually dimorphic spinal GRP neurons controlling male sexual function were clearly labeled with Venus fluorescence. As expected, Venus fluorescence in the male lumbar cord was markedly decreased after castration and restored by chronic androgen replacement. Furthermore, androgen-induced Venus expression in the spinal cord of adult Tg males was significantly attenuated by chronic treatment with progesterone but not with estradiol. A luciferase assay using a human GRP-promoter construct showed that androgens enhance the spinal GRP system, and more strikingly, that progesterone acts to inhibit the GRP system via an androgen receptor-mediated mechanism. These results demonstrate that circulating androgens may play an important role in the spinal GRP system controlling male sexual function not only in rats but also in humans and that progesterone could be an important feminizing factor in the spinal GRP system in females during pubertal development.

  8. Steroids in house sparrows (Passer domesticus): Effects of POPs and male quality signalling.

    Science.gov (United States)

    Nossen, Ida; Ciesielski, Tomasz M; Dimmen, Malene V; Jensen, Henrik; Ringsby, Thor Harald; Polder, Anuschka; Rønning, Bernt; Jenssen, Bjørn M; Styrishave, Bjarne

    2016-03-15

    At high trophic levels, environmental contaminants have been found to affect endocrinological processes. Less attention has been paid to species at lower trophic levels. The house sparrow (Passer domesticus) may be a useful model for investigating effects of POPs in mid-range trophic level species. In male house sparrows, ornamental traits involved in male quality signalling are important for female selection. These traits are governed by endocrinological systems, and POPs may therefore interfere with male quality signalling. The aim of the present study was to use the house sparrow as a mid-range trophic level model species to study the effects of environmental contaminants on endocrinology and male quality signalling. We analysed the levels of selected PCBs, PBDEs and OCPs and investigated the possible effects of these contaminants on circulating levels of steroid hormones (4 progestagens, 4 androgens and 3 estrogens) in male and female adult house sparrows from a population on the island Leka, Norway. Plasma samples were analysed for steroid hormones by GC-MS and liver samples were analysed for environmental contaminants by GC-ECD and GC-MS. In males, we also quantified ornament traits. It was hypothesised that POPs may have endocrine disrupting effects on the local house sparrow population and can thus interfere with the steroid hormone homeostasis. Among female house sparrows, bivariate correlations revealed negative relationships between POPs and estrogens. Among male sparrows, positive relationships between dihydrotestosterone levels and PCBs were observed. In males, positive relationships were also found between steroids and beak length, and between steroids and ornamental traits such as total badge size. This was confirmed by a significant OPLS model between beak length and steroids. Although sparrows are in the mid-range trophic levels, the present study indicates that POPs may affect steroid homeostasis in house sparrows, in particular for females. For

  9. Steroid hormones as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1988-01-01

    Glucocorticoid and mineralocorticoid receptors are present in normal epithelial cells of both the small and large intestine and there have also been contentious reports of androgen, oestrogen and progesterone receptors in the epithelium of the normal large intestine. The majority of reports suggest that stimulation of the intestinal glucocorticoid receptors results in increased proliferation of epithelial cells in the small bowel, as does stimulation of androgen receptors and possibly mineralocorticoid receptors. The proliferative response of the normal intestine to oestrogens is difficult to evaluate and that to progestigens appears not to have been reported. Epidemiological studies reveal a higher incidence of bowel cancer in premenopausal women than in men of the same age and yet there is a lower incidence of these tumors in women of higher parity. These findings have been atributted to a variety of non-epithelial gender characteristic such as differences in bile metabolism, colonic bacterial and fecal transit times. In experimental animals, androgens have also been shown to influence carcinogenesis and this could well be attributed to changes in food intake etc. However, many studies have now revealed steroid hormone receptors on colorectal tumor cells and thus a direct effect of the steroid hormones on the epithelium during and after malignant transformation must now be considered.

  10. Modulation of Androgen Receptor Transcriptional Activity

    NARCIS (Netherlands)

    H.Y. Wong (Hao Yun)

    2009-01-01

    textabstractAndrogens, testosterone (T) and 5a-dihydrotestosterone (DHT), are important for male and female physiology, in particular for male sexual differentiation, development of secondary male characteristics and spermatogenesis. These hormones exert their actions by binding to the androgen

  11. Steroid hormone and epidermal growth factor receptors in meningiomas.

    Science.gov (United States)

    Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

    1989-11-01

    A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

  12. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Skovbjerg Arildsen, Nicolai; Malander, Susanne

    2015-01-01

    BACKGROUND AND AIMS: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival...... in epithelial ovarian cancer. METHODS: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer...... in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer....

  13. Androgens and the ageing male

    DEFF Research Database (Denmark)

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-specific and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term...... 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do...

  14. High-throughput bioaffinity mass spectrometry for screening and identification of designer anabolic steroids in dietary supplements.

    Science.gov (United States)

    Aqai, Payam; Cevik, Ebru; Gerssen, Arjen; Haasnoot, Willem; Nielen, Michel W F

    2013-03-19

    A generic high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS) approach was developed and applied for the screening and identification of known and unknown recombinant human sex hormone-binding globulin (rhSHBG)-binding designer steroids in dietary supplements. For screening, a semi-automated competitive inhibition binding assay was combined with fast ultrahigh-performance-LC-electrospray ionization-triple-quadrupole-MS (UPLC-QqQ-MS). 17β-Testosterone-D3 was used as the stable isotope label of which the binding to rhSHBG-coated paramagnetic microbeads was inhibited by any other binding (designer) steroid. The assay was performed in a 96-well plate and combined with the fast LC-MS, 96 measurements could be performed within 4 h. The concentration-dependent inhibition of the label by steroids in buffer and dietary supplements was demonstrated. Following an adjusted bioaffinity isolation procedure, suspect extracts were injected into a chip-UPLC(NanoTile)-Q-time-of-flight-MS system for full-scan accurate mass identification. Next to known steroids, 1-testosterone was identified in three of the supplements studied and the designer steroid tetrahydrogestrinone was identified in a spiked supplement. The generic steroid-binding assay can be used for high-throughput screening of androgens, estrogens, and gestagens in dietary supplements to fight doping. When combined with chip-UPLC-MS, it is a powerful tool for early warning of unknown emerging rhSHBG bioactive designer steroids in dietary supplements.

  15. Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens.

    Science.gov (United States)

    Cappelletti, Maurand; Wallen, Kim

    2016-02-01

    Both estradiol and testosterone have been implicated as the steroid critical for modulating women's sexual desire. By contrast, in all other female mammals only estradiol has been shown to be critical for female sexual motivation and behavior. Pharmaceutical companies have invested heavily in the development of androgen therapies for female sexual desire disorders, but today there are still no FDA approved androgen therapies for women. Nonetheless, testosterone is currently, and frequently, prescribed off-label for the treatment of low sexual desire in women, and the idea of testosterone as a possible cure-all for female sexual dysfunction remains popular. This paper places the ongoing debate concerning the hormonal modulation of women's sexual desire within a historical context, and reviews controlled trials of estrogen and/or androgen therapies for low sexual desire in postmenopausal women. These studies demonstrate that estrogen-only therapies that produce periovulatory levels of circulating estradiol increase sexual desire in postmenopausal women. Testosterone at supraphysiological, but not at physiological, levels enhances the effectiveness of low-dose estrogen therapies at increasing women's sexual desire; however, the mechanism by which supraphysiological testosterone increases women's sexual desire in combination with an estrogen remains unknown. Because effective therapies require supraphysiological amounts of testosterone, it remains unclear whether endogenous testosterone contributes to the modulation of women's sexual desire. The likelihood that an androgen-only clinical treatment will meaningfully increase women's sexual desire is minimal, and the focus of pharmaceutical companies on the development of androgen therapies for the treatment of female sexual desire disorders is likely misplaced. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Topical steroid-damaged skin

    Directory of Open Access Journals (Sweden)

    Anil Abraham

    2014-01-01

    Full Text Available Topical steroids, commonly used for a wide range of skin disorders, are associated with side effects both systemic and cutaneous. This article aims at bringing awareness among practitioners, about the cutaneous side effects of easily available, over the counter, topical steroids. This makes it important for us as dermatologists to weigh the usefulness of topical steroids versus their side effects, and to make an informed decision regarding their use in each individual based on other factors such as age, site involved and type of skin disorder.

  17. The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study.

    Science.gov (United States)

    Goudarzi, Houman; Araki, Atsuko; Itoh, Sachiko; Sasaki, Seiko; Miyashita, Chihiro; Mitsui, Takahiko; Nakazawa, Hiroyuki; Nonomura, Katsuya; Kishi, Reiko

    2017-01-01

    Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans. We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones. We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother-infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way. We found a dose-response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were -23.98-ng/mL (95% CI: -0.47.12, -11.99; p for trend = 0.006) and -63.21-ng/mL (95% CI: -132.56, -26.72; p for trend blood. Citation: Goudarzi H, Araki A, Itoh S, Sasaki S, Miyashita C, Mitsui T, Nakazawa H, Nonomura K, Kishi R. 2017. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: the Hokkaido Study. Environ Health Perspect 125:111-118; http://dx.doi.org/10.1289/EHP142.

  18. Androgen Receptor Involvement in Rat Amelogenesis: An Additional Way for Endocrine-Disrupting Chemicals to Affect Enamel Synthesis.

    Science.gov (United States)

    Jedeon, Katia; Loiodice, Sophia; Salhi, Khaled; Le Normand, Manon; Houari, Sophia; Chaloyard, Jessica; Berdal, Ariane; Babajko, Sylvie

    2016-11-01

    Endocrine-disrupting chemicals (EDCs) that interfere with the steroid axis can affect amelogenesis, leading to enamel hypomineralization similar to that of molar incisor hypomineralization, a recently described enamel disease. We investigated the sex steroid receptors that may mediate the effects of EDCs during rat amelogenesis. The expression of androgen receptor (AR), estrogen receptor (ER)-α, and progesterone receptor was dependent on the stage of ameloblast differentiation, whereas ERβ remained undetectable. AR was the only receptor selectively expressed in ameloblasts involved in final enamel mineralization. AR nuclear translocation and induction of androgen-responsive element-containing promoter activity upon T treatment, demonstrated ameloblast responsiveness to androgens. T regulated the expression of genes involved in enamel mineralization such as KLK4, amelotin, SLC26A4, and SLC5A8 but not the expression of genes encoding matrix proteins, which determine enamel thickness. Vinclozolin and to a lesser extent bisphenol A, two antiandrogenic EDCs that cause enamel defects, counteracted the actions of T. In conclusion, we show, for the first time, the following: 1) ameloblasts express AR; 2) the androgen signaling pathway is involved in the enamel mineralization process; and 3) EDCs with antiandrogenic effects inhibit AR activity and preferentially affect amelogenesis in male rats. Their action, through the AR pathway, may specifically and irreversibly affect enamel, potentially leading to the use of dental defects as a biomarker of exposure to environmental pollutants. These results are consistent with the steroid hormones affecting ameloblasts, raising the issue of the hormonal influence on amelogenesis and possible sexual dimorphism in enamel quality.

  19. Fate and occurrence of steroids in swine and dairy cattle farms with different farming scales and wastes disposal systems

    International Nuclear Information System (INIS)

    Liu Shan; Ying Guangguo; Zhang Ruiquan; Zhou Lijun; Lai Huajie; Chen Zhifeng

    2012-01-01

    Fate and occurrence of fourteen androgens, four estrogens, five glucocorticoids and five progestagens were investigated in three swine farms and three dairy cattle farms with different farming scales and wastes disposal systems in China. Twenty-one, 22, and 12 of total 28 steroids were detected in feces samples with concentrations ranging from below method limit of quantitation (< LOQ for estrone) to 8100 ± 444 ng/g (progesterone), in wastewater samples with concentrations ranging from < LOQ (estrone) to 20,700 ± 1490 ng/L (androsterone), in suspended particles with concentrations ranging from < LOQ (17β-trenbolone) to 778 ± 82.1 ng/g (5α-dihydrotestosterone) in the six farms, respectively. The steroids via swine farms and human sources were mainly originated from wastewater into the receiving environments while those steroids via cattle farms were mainly from cattle feces. The total contributions of steroids to the environment in China are estimated to be 139, 65.8 and 60.7 t/year from swine, dairy cattle and human sources, respectively. - Highlights: ► 28 steroids were investigated in three swine farms and three cattle farms. ► Eight detected synthetic steroids were from exogenous usage. ► Lagoon systems were more effective in removing steroids than sedimentation tanks. ► The steroids via swine and human sources were mainly from wastewater. ► The steroids via cattle were mainly originated from feces. - The swine and cattle farms contribute higher steroids masses to the environment than the human sources.

  20. Development of a GC/C/IRMS method--confirmation of a novel steroid profiling approach in doping control.

    Science.gov (United States)

    Van Renterghem, Pieter; Polet, Michael; Brooker, Lance; Van Gansbeke, Wim; Van Eenoo, Peter

    2012-09-01

    In doping control, an athlete can only be convicted with the misuse with endogenous steroids like testosterone (T), if abnormal values of steroid metabolites and steroid ratios are observed and if the subsequent analysis with isotope ratios mass spectrometry (IRMS) confirms the presence of exogenously administered androgens. In this work, we compare the results of a novel steroid profiling approach with the performance an in-house developed IRMS method. The developed IRMS has the advantage over other methods to be relatively short in time and with target compounds androsterone, etiocholanolone, 5β-androstane 3α,17β-diol and 5α-androstane 3α,17β-diol. Pregnanediol was used as an endogenous reference compound (ERC). Reference limits for the IRMS values were established and applied as decision limits for the evaluation of excretion urine from administration with oral T, T-gel, dihydrotestosterone (DHT) - gel and dehydroepiandrosterone (DHEA). Results indicated the importance of both androstanediols as important IRMS markers where relative values compared to an ERC (Δδ(13)C) yielded better detection accuracy than absolute δ(13)C-values. The detection times of all administered endogenous steroids were evaluated using the proposed thresholds. The results of traditional steroid profiling and a new approach based upon minor steroid metabolites monitoring introduced in a longitudinal framework were evaluated with IRMS. With traditional steroid profiling methods, 95% of the atypical samples could be confirmed whereas an additional 74% of IRMS confirmed was provided by a new biomarkers strategy. These results prove that the other steroid profiling strategies can improve the efficiency in detection of misuse with endogenous steroids. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Regucalcin expression in bovine tissues and its regulation by sex steroid hormones in accessory sex glands.

    Directory of Open Access Journals (Sweden)

    Laura Starvaggi Cucuzza

    Full Text Available Regucalcin (RGN is a mammalian Ca2+-binding protein that plays an important role in intracellular Ca2+ homeostasis. Recently, RGN has been identified as a target gene for sex steroid hormones in the prostate glands and testis of rats and humans, but no studies have focused on RGN expression in bovine tissues. Thus, in the present study, we examined RGN mRNA and protein expression in the different tissues and organs of veal calves and beef cattle. Moreover, we investigated whether RGN expression is controlled through sex steroid hormones in bovine target tissues, namely the bulbo-urethral and prostate glands and the testis. Sex steroid hormones are still illegally used in bovine husbandry to increase muscle mass. The screening of the regulation and function of anabolic sex steroids via modified gene expression levels in various tissues represents a new approach for the detection of illicit drug treatments. Herein, we used quantitative PCR, western blot and immunohistochemistry analyses to demonstrate RGN mRNA and protein expression in bovine tissues. In addition, estrogen administration down-regulated RGN gene expression in the accessory sex glands of veal calves and beef cattle, while androgen treatment reduced RGN gene expression only in the testis. The confirmation of the regulation of RGN gene expression through sex steroid hormones might facilitate the potential detection of hormone abuse in bovine husbandry. Particularly, the specific response in the testis suggests that this tissue is ideal for the detection of illicit androgen administration in veal calves and beef cattle.

  2. Transport of steroid hormones, phytoestrogens, and estrogenic activity across a swine lagoon/sprayfield system.

    Science.gov (United States)

    Yost, Erin E; Meyer, Michael T; Dietze, Julie E; Williams, C Michael; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W

    2014-10-07

    The inflow, transformation, and attenuation of natural steroid hormones and phytoestrogens and estrogenic activity were assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive stages, with progesterone being the most abundant steroid hormone. Excreta also contained phytoestrogens indicative of a soy-based diet, particularly, daidzein, genistein, and equol. During storage in barn pits and the anaerobic lagoon, conjugated hormones dissipated, and androgens and progesterone were attenuated. Estrone and equol persisted along the waste disposal route. Following application of lagoon slurry to agricultural soils, all analytes exhibited attenuation within 2 days. However, analytes including estrone, androstenedione, progesterone, and equol remained detectable in soil at 2 months postapplication. Estrogenic activity in the yeast estrogen screen and T47D-KBluc in vitro bioassays generally tracked well with analyte concentrations. Estrone was found to be the greatest contributor to estrogenic activity across all sample types. This investigation encompasses the most comprehensive suite of natural hormone and phytoestrogen analytes examined to date across a livestock lagoon/sprayfield and provides global insight into the fate of these analytes in this widely used waste management system.

  3. Sex steroids and the GH axis: Implications for the management of hypopituitarism.

    Science.gov (United States)

    Birzniece, Vita; Ho, Ken K Y

    2017-02-01

    Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Sex hormones exert profound effect on the secretion and action of GH. Estrogens stimulate the secretion of GH, but inhibit the action of GH on the liver, an effect that occurs when administered orally. Estrogens suppress GH receptor signaling by stimulating the expression proteins that inhibit cytokine receptor signaling. This effect of estrogens is avoided when physiological doses of estrogens are administered via a non-oral route. Estrogen-like compounds, such as selective estrogen receptor modulators, possess dual properties of inhibiting the secretion as well as the action of GH. In contrast, androgens stimulate GH secretion, driving IGF-1 production. In the periphery, androgens enhance the action of GH. The differential effects of estrogens and androgens influence the dose of GH replacement in patients with hypopituitarism on concomitant treatment with sex steroids. Where possible, a non-oral route of estrogen replacement is recommended for optimizing cost-benefit of GH replacement in women with GH deficiency. Adequate androgen replacement in conjunction with GH replacement is required to achieve the full anabolic effect in men with hypopituitarism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    NARCIS (Netherlands)

    D. Chadha; T.D. Pache; F.J. Huikeshoven (Frans); A.O. Brinkmann (Albert); Th.H. van der Kwast (Theo)

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated

  5. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2006-01-01

    .... Intermittent androgen ablation therapy (IAAT) may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  6. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2004-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  7. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2005-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  8. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2003-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  9. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

    Science.gov (United States)

    Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

    2008-07-01

    Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells.

  10. Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary.

    Science.gov (United States)

    Fowler, Paul A; Anderson, Richard A; Saunders, Philippa T; Kinnell, Hazel; Mason, J Ian; Evans, Dean B; Bhattacharya, Siladitya; Flannigan, Samantha; Franks, Stephen; Monteiro, Ana; O'Shaughnessy, Peter J

    2011-06-01

    Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking. The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary. We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members. The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow. Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies. We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1. Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells. The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.

  11. Circadian Rhythm of Hepatic Cytosolic and Nuclear Estrogen and Androgen Receptors

    Science.gov (United States)

    FRANCAVILLA, ANTONIO; EAGON, PATRICIA K.; DiLEO, ALFREDO; VAN THIEL, DAVID H.; PANELLA, CARMINE; POLIMENO, LORENZO; AMORUSO, CINZIA; INGROSSO, MARCELLO; AQUILINO, A. MARIA; STARZL, THOMAS E.

    2010-01-01

    Mammalian liver is a sex steroid-responsive tissue. The effects of these hormones presumably are mediated by hepatic estrogen receptors (ER) and androgen receptors (AR). Serum levels of sex hormones display circadian rhythms. Further, estrogens and androgens are commonly administered; administration of these agents is associated frequently with liver disease. Therefore, we investigated whether the cytosolic and nuclear sex steroid receptors also display a similar circadian rhythm, and whether variations occurred in the distribution of receptors between cytosolic and nuclear compartments. Animals were killed every 4 h from midnight till the following midnight; cytosolic and nuclear levels of both ER and AR were measured. Cytosolic ER reached a maximum level at 4 AM, and a minimum at 8 PM and midnight of both days. Nuclear ER was highest at 8 AM and lowest at 4 PM and 8 PM, a pattern which parallels variations in serum estradiol levels. Cytosolic AR was highest at 8 PM and lowest at midnight and 4 AM. Nuclear AR was highest at 4 AM and lowest at 4 PM and 8 PM. The highest level of nuclear AR does not correspond to the maximum serum testosterone level, which occurred at 4 PM. The total hepatic content of both ER and AR was not constant over the 24-h period, but varied considerably with time of day. These studies suggest that both ER and AR show a distinct circadian rhythm in subcellular compartmentalization, and that total hepatic content of ER and AR varies significantly during a 24-h period. PMID:3710067

  12. Characteristics and Behaviors of Older Male Anabolic Steroid Users.

    Science.gov (United States)

    Ip, Eric J; Trinh, Karen; Tenerowicz, Michael J; Pal, Jai; Lindfelt, Tristan A; Perry, Paul J

    2015-10-01

    To compare and contrast the characteristics of 2 groups of men ≥40 years old: reported anabolic-androgenic steroid (AAS) users and nonusers. Cross-sectional survey. Thirty-eight online fitness, weight lifting, bodybuilding, and steroid Web sites. A total of 67 male AAS users and 76 male nonusers ≥40 years old. Demographics, utilization of AAS and other performance-enhancing agents (PEAs), exercise patterns, history of illicit drugs and alcohol use, and psychiatric traits/diagnoses. The majority of AAS users ≥40 years old were caucasian (92.5%), heterosexual (97.0%), and classified themselves as recreational exercisers (79.1%). AAS users took more PEAs (11.5 ± 5.6 vs 4.6 ± 2.7; P aggressive alcohol use, and a higher incidence of substance dependence and anxiety disorders compared to nonusers. This information may help clinicians and researchers identify and develop appropriate intervention strategies for AAS abuse among older men. © The Author(s) 2014.

  13. The effects of smoking on steroid metabolism and fetal programming.

    Science.gov (United States)

    Dušková, M; Hruškovičová, H; Šimůnková, K; Stárka, L; Pařízek, A

    2014-01-01

    Tobacco addiction is a serious psychosocial and health problem. A pregnant woman who smokes not only influences the maternal organism, but also passes health risks on to the unborn child. A fetus exposed to maternal smoking is not only directly influenced, but is also endangered by a wide range of diseases up to his or her adult years. The components of tobacco smoke play a significant role in the development of a number of diseases for a large proportion of the smoking population, as well as among those pregnant. This article summarizes findings regarding the impacts on the production of steroid hormones - first describing the smoking-related changes in steroidogenesis in women, and then focusing on the influence of maternal smoking on the fetus's developing steroidogenesis. We assume that if during prenatal development the fetus has already been exposed to the effect of endocrine disruptors at the time fetal steroidogenesis begins fetal programming, this exposure can have serious pathophysiological effects both in the pregnancy as well as later in life. An example of such effects might be a delay in the creation of kidney adrenal androgens, which could also be evident on the level of steroid neuroactive metabolites that may influence the individual's psychological state and lead to later addictions. Copyright © 2013. Published by Elsevier Ltd.

  14. Androgen radioimmunoassay in the ram: results of direct plasma testosterone and dehydroepiandrosterone measurement and physiological evaluation

    International Nuclear Information System (INIS)

    Garnier, D.-H.; Cotta, Y.; Terqui, M.

    1978-01-01

    Different radioimmunoassays of testosterone (T) dehydroepiandrosterone (DHA) and 5 α-dihydrotestosterone (5 α-DHT) were investigated for ram plasma. Specificity of the antisera, lack of noticeable binding in plasma, very low levels of other androgens allow direct plasma RIA for DHA and T by the double antibody technique. The levels obtained by this simplified method are in agreement with those found after extraction alone, after extraction and celite chromatography and after quantification with a completely different technique such as gas chromatography. The within assay variabilities for T and DHA were 4.7 p. 100 and 4.6 p. 100 respectively but vary with the level of steroid in plasma. The inter assay variabilities of T were 9.5 p. 100 and 3.2 p. 100 for 1.5 and 11.6 ng/ml of plasma respectively. The antiserum for 5 α-DHT have a specificity such that, even after celite chromatography some androgens (5 β-DHT) may interfere. However determinations of 5 α/5 β-DHT amounts are possible. The physiological validations of direct plasma T and DHA RIA were studied in various conditions. The DHA plasma variations are similar to those of T in Ram from birth to puberty, but the levels are lower. DHA plasma levels show a seasonal variation as does testosterone. Variations within 24 hrs of these two androgens were in synchrony. The direct plasma T and DHA assays are useful and inexpensive tools to characterize ram testicular function

  15. Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jae-Kyung Myung

    Full Text Available Androgen receptor (AR is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD. Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

  16. Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors

    International Nuclear Information System (INIS)

    Chang, C.; Kokontis, J.; Liao, S.

    1988-01-01

    Structural analysis of cDNAs for human and rat androgen receptors (ARs) indicates that the amino-terminal regions of ARs are rich in oligo- and poly(amino acid) motifs as in some homeotic genes. The human AR has a long stretch of repeated glycines, whereas rat AR has a long stretch of glutamines. There is a considerable sequence similarity among ARs and the receptors for glucocorticoids, progestins, and mineralocorticoids within the steroid-binding domains. The cysteine-rich DNA-binding domains are well conserved. Translation of mRNA transcribed from AR cDNAs yielded 94- and 76-kDa proteins and smaller forms that bind to DNA and have high affinity toward androgens. These rat or human ARs were recognized by human autoantibodies to natural Ars. Molecular hybridization studies, using AR cDNAs as probes, indicated that the ventral prostate and other male accessory organs are rich in AR mRNA and that the production of AR mRNA in the target organs may be autoregulated by androgens

  17. Maternal androgens in avian brood parasites and their hosts: responses to parasitism and competition?

    Science.gov (United States)

    Hahn, Caldwell; Wingfield, John C.; Fox, David M.; Walker, Brian G.; Thomley, Jill E

    2017-01-01

    In the coevolutionary dynamic of avian brood parasites and their hosts, maternal (or transgenerational) effects have rarely been investigated. We examined the potential role of elevated yolk testosterone in eggs of the principal brood parasite in North America, the brown-headed cowbird, and three of its frequent host species. Elevated maternal androgens in eggs are a common maternal effect observed in many avian species when breeding conditions are unfavorable. These steroids accelerate embryo development, shorten incubation period, increase nestling growth rate, and enhance begging vigor, all traits that can increase the survival of offspring. We hypothesized that elevated maternal androgens in host eggs are a defense against brood parasitism. Our second hypothesis was that elevated maternal androgens in cowbird eggs are a defense against intra-specific competition. For host species, we found that elevated yolk testosterone was correlated with parasitized nests of small species, those whose nest success is most reduced by cowbird parasitism. For cowbirds, we found that elevated yolk testosterone was correlated with eggs in multiply-parasitized nests, which indicate intra-specific competition for nests due to high cowbird density. We propose experimental work to further examine the use of maternal effects by cowbirds and their hosts.

  18. Functional behavior and reproduction in androgenic sex reversed zebrafish (Danio rerio).

    Science.gov (United States)

    Larsen, Mia G; Baatrup, Erik

    2010-08-01

    Endocrine-disrupting chemicals released into natural watercourses may cause biased sex ratios by sex reversal in fish populations. The present study investigated the androgenic sex reversal of zebrafish (Danio rerio) exposed to the androgenic compound 17beta-trenbolone (TB) and whether sex-changed females would revert to the female phenotype after cessation of TB exposure. 17beta-Trenbolone is a metabolite of trenbolone acetate, an anabolic steroid used as a growth promoter in beef cattle. 17beta-Trenbolone in runoff from cattle feedlots may reach concentrations that affect fish sexual development. Zebrafish were exposed to a concentration of 20 ng/L TB in a flow-through system for five months from egg until sexual maturity. This resulted in an all-male population. It was further found that all these phenotypic males displayed normal male courtship behavior and were able to reproduce successfully, implying that the sex reversal was complete and functional. None of the phenotypic males developed into females after six months in clean water, demonstrating that androgenic sex reversal of zebrafish is irreversible. Copyright 2010 SETAC

  19. Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

    Science.gov (United States)

    Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

    2004-02-12

    A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

  20. History and epidemiology of anabolic androgens in athletes and non-athletes.

    Science.gov (United States)

    Kanayama, Gen; Pope, Harrison G

    2018-03-15

    The use of androgens, frequently referred to as anabolic-androgenic steroids (AAS), has grown into a worldwide substance abuse problem over the last several decades. Testosterone was isolated in the 1930s, and numerous synthetic androgens were quickly developed thereafter. Athletes soon discovered the dramatic anabolic effects of these hormones, and AAS spread rapidly through elite athletics and bodybuilding from the 1950s through the 1970s. However it was not until the 1980s that widespread AAS use emerged from the elite athletic world and into the general population. Today, the great majority of AAS users are not competitive athletes, but instead are typically young to middle-aged men who use these drugs primarily for personal appearance. AAS abuse has now become particularly prevalent in regions such as Scandinavia, the United States, Brazil, and British Commonwealth countries, but remains rare in countries such as China, Korea, and Japan - a pattern that reflects cultural differences in attitudes towards male muscularity. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Prostate cancer characteristics associated with response to pre-receptor targeting of the androgen axis.

    Directory of Open Access Journals (Sweden)

    Elahe A Mostaghel

    Full Text Available Factors influencing differential responses of prostate tumors to androgen receptor (AR axis-directed therapeutics are poorly understood, and predictors of treatment efficacy are needed. We hypothesized that the efficacy of inhibiting DHT ligand synthesis would associate with intra-tumoral androgen ratios indicative of relative dependence on DHT-mediated growth.We characterized two androgen-sensitive prostate cancer xenograft models after androgen suppression by castration in combination with the SRD5A inhibitor, dutasteride, as well as a panel of castration resistant metastases obtained via rapid autopsy.In LuCaP35 tumors (intra-tumoral T:DHT ratio 2:1 dutasteride suppressed DHT to 0.02 ng/gm and prolonged survival vs. castration alone (337 vs.152 days, HR 2.8, p = 0.0015. In LuCaP96 tumors (T:DHT 10:1, survival was not improved despite similar DHT reduction (0.02 ng/gm. LuCaP35 demonstrated higher expression of steroid biosynthetic enzymes maintaining DHT levels (5-fold higher SRD5A1, 41 fold higher, 99-fold higher RL-HSD, p<0.0001 for both, reconstitution of intra-tumoral DHT (to ∼30% of untreated tumors, and ∼2 fold increased expression of full length AR. In contrast, LuCaP96 demonstrated higher levels of steroid catabolizing enzymes (6.9-fold higher AKR1C2, 3000-fold higher UGT2B15, p = 0.002 and p<0.0001 respectively, persistent suppression of intra-tumoral DHT, and 6-8 fold induction of full length AR and the ligand independent V7 AR splice variant. Human metastases demonstrated bio-active androgen levels and AR full length and AR splice-variant expression consistent with the range observed in xenografts.Intrinsic differences in basal steroidogenesis, as well as variable expression of full length and splice-variant AR, associate with response and resistance to pre-receptor AR ligand suppression. Expression of steroidogenic enzymes and AR isoforms may serve as potential biomarkers of sensitivity to potent AR-axis inhibition and

  2. BILATERAL STEROID INDUCED GLAUCOMA IN VERNAL KERATOCONJUNCTIVITIS

    Directory of Open Access Journals (Sweden)

    Bangal Surekha V, Bankar Mahima S, Bhandari Akshay J, Kalkote Prasad R

    2015-01-01

    Full Text Available Vernal Keratoconjunctivits (VKC is a bilateral recurrent allergic interstitial conjunctival inflammation with a periodic seasonal incidence and of self limiting nature, mainly affecting the younger population. Patients of VKC on steroid therapy are at higher risk of developing steroid induced glaucoma. Raised intraocular pressure due to steroids typically occurs within few weeks of starting steroid therapy and comes back to normal on immediate stoppage of steroids. A case of steroid induced glaucoma in a 30 years old female with vernal keratoconjunctivitis. She was on topical steroids for 3-4 years. She was incompliant with the instructions to stop steroids. She eventually developed steroid induced glaucoma and glaucomatous optic neuropathy with tunnel vision.

  3. ["No" for stacked young bodybuilders, "yes" for manthers: the biomedical discourse on anabolic steroids and health].

    Science.gov (United States)

    Moraes, Danielle Ribeiro de; Castiel, Luis David; Ribeiro, Ana Paula Pereira da Gama Alves

    2015-06-01

    The article addresses the use of anabolic androgenic steroids (AAS), synthetic drugs whose abuse has been characterized as a public health problem, operated in the opposition between "medical" and "non-medical" uses. A qualitative approach was used to analyze the text in 76 biomedical articles published from 2002 to 2012. The discourse shows a persistent ban on non-medically regulated use of AAS by young people, while the limits on clinically qualified use appear to expand among older people, even given the contradictions straining the argument on the prevention of health risks. Moralizing biopolitical stances appear, based on gender distinctions or under the aegis of criminalizing drug use.

  4. Three siblings with complete androgen insensitivity syndrome

    African Journals Online (AJOL)

    2013-01-13

    Jan 13, 2013 ... male reference range. A diagnosis of complete androgen insensitivity syndrome was made, based on this clinical ... Laboratory test. Value Normal ..... scenario, incomplete resistance may lead to virilisation during puberty.24, ...

  5. A Novel Mechanism of Androgen Receptor Action

    National Research Council Canada - National Science Library

    Roberts, Jr, Charles T

    2006-01-01

    .... Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA...

  6. Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy.

    Science.gov (United States)

    Ponnusamy, Suriyan; Sullivan, Ryan D; You, Dahui; Zafar, Nadeem; He Yang, Chuan; Thiyagarajan, Thirumagal; Johnson, Daniel L; Barrett, Maron L; Koehler, Nikki J; Star, Mayra; Stephenson, Erin J; Bridges, Dave; Cormier, Stephania A; Pfeffer, Lawrence M; Narayanan, Ramesh

    2017-07-01

    Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly affects boys as a result of mutation(s) in the dystrophin gene. DMD is characterized by musculoskeletal and cardiopulmonary complications, resulting in shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5 years of age and declining physical functions before attaining puberty. We hypothesized that rapidly deteriorating health of pre-pubertal boys with DMD could be due to diminished anabolic actions of androgens in muscle, and that intervention with an androgen receptor (AR) agonist will reverse musculoskeletal complications and extend survival. While castration of dystrophin and utrophin double mutant (mdx-dm) mice to mimic pre-pubertal nadir androgen condition resulted in premature death, maintenance of androgen levels extended the survival. Non-steroidal selective-AR modulator, GTx-026, which selectively builds muscle and bone was tested in X-linked muscular dystrophy mice (mdx). GTx-026 significantly increased body weight, lean mass and grip strength by 60-80% over vehicle-treated mdx mice. While vehicle-treated castrated mdx mice exhibited cardiopulmonary impairment and fibrosis of heart and lungs, GTx-026 returned cardiopulmonary function and intensity of fibrosis to healthy control levels. GTx-026 elicits its musculoskeletal effects through pathways that are distinct from dystrophin-regulated pathways, making AR agonists ideal candidates for combination approaches. While castration of mdx-dm mice resulted in weaker muscle and shorter survival, GTx-026 treatment increased the muscle mass, function and survival, indicating that androgens are important for extended survival. These preclinical results support the importance of androgens and the need for intervention with AR agonists to treat DMD-affected boys. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Lonidamine affects testicular steroid hormones in immature mice

    International Nuclear Information System (INIS)

    Traina, Maria Elsa; Guarino, Maria; Natoli, Alessia; Romeo, Antonella; Urbani, Elisabetta

    2007-01-01

    The effects on the hypothalamus-pituitary-testicular axis of the well-known antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the present study, the possible changes of the testicular steroid hormones were evaluated in immature mice for a better characterization of the LND adverse effects both in its use as antitumoral agent and male contraceptive. Male CD1 mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or 100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on PND42 (1 and 2 weeks after the administration, respectively). Severe testicular effects were evidenced in the LND treated groups, including: a) significant testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease (more than 50% of the control) on PND29-32; c) damage of the tubule morphology primarily on the Sertoli cell structure and germ cell exfoliation. All these reproductive endpoints were recovered on PND42. At the same time, a significant impairment of the testicular steroid balance was observed in the treated mice, as evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while the testicular content of 17β-estradiol (E2) was unchanged. The hormonal balance was not completely restored afterwards, as levels of T, ADIONE and 17OH-P4 tended to be higher in the treated mice than in the controls, on PND35 and PND42. These data showed for the first time that LND affects intratesticular steroids in experimental animals. However further data are needed both to elucidate the mechanism responsible for the impairment of these metabolic pathways and to understand if the androgens decrease observed after LND administration could be partially involved in the testicular damage

  8. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.

    2000-01-01

    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

  9. "Will steroids kill me if I use them once?" A qualitative analysis of inquiries submitted to the Danish anti-doping authorities

    DEFF Research Database (Denmark)

    Christiansen, Ask Vest; Bojsen-Møller, Jens

    2012-01-01

    categories of inquiries were the focus of attention: 1) those addressing side effects of anabolic steroids, and 2) those addressing concerns for receiving a positive doping test after the use of supplements. Results and discussion: In the first category four different types of approaches were identified...... and inquirers' concerns analysed: a) those that lacked knowledge on anabolic steroids, b) those that had experienced side effects, c) those that expressed knowledge of anabolic steroids, and d) those that presented potential harm reduction dilemmas for the counselling service. The second category revealed......Background: The Danish strategy for fighting the use of anabolic androgenic steroids in fitness centres is likely the most comprehensive of its sort in the world. It is instituted in the national anti doping organisation, Anti Doping Denmark (ADD), and consists of doping controls, educational...

  10. Two simple cleanup methods combined with LC-MS/MS for quantification of steroid hormones in in vivo and in vitro assays

    DEFF Research Database (Denmark)

    Weisser, Johan Juhl; Hansen, Cecilie Hurup; Poulsen, Rikke

    2016-01-01

    Measuring both progestagens, androgens, corticosteroids as well as estrogens with a single method makes it possible to investigate the effects of endocrine-disrupting chemicals (EDCs) on the main pathways in the mammalian steroidogenesis. This paper presents two simple methods for the determination...... of the major steroid hormones in biological matrixes using liquid chromatography tandem mass spectrometry (LC-MS(2)). A novel method was developed for the determination of 14 steroids in the H295R in vitro assay without the need for solid phase extraction (SPE) purification prior to LC-MS(2) analysis....... The in vitro assay was validated by exposing H295R cells to prochloraz for inhibiting steroid hormone secretion and by exposing cells to forskolin for inducing steroid hormone secretion. The developed method fulfills the recommendations for the H295R assay suggested by the OECD. Furthermore, a simple off...

  11. A Simple Thin Layer Chromatography Method for Separation of Selected Natural Steroid Hormones

    International Nuclear Information System (INIS)

    Nowakowska, J.; Rudnicka-Litka, K.; Ciura, K.; Pikul, P.; Piotrowicz, J.

    2015-01-01

    Chromatographic properties of seven steroids: estrogens (β-estradiol and estrone), androgens (testosterone, methyltestosterone, trans-androsterone), progesterone and cholesterol have been studied by planar chromatography with usage of High Performance Thin Layer Chromatography (HPTLC) and Thin Layer Chromatography (TLC) plates. Normal, reversed and cyano-bonded silica stationary phases were tested with five binary mobile phases (acetonitrile-water, acetonitrile-DMSO, acetonitrile-methanol, acetone-petroleum ether, acetone-water) in which the concentration of organic modifier varied from 0 to 100 % (v/v). This study reports the optimization of steroid hormones separation. Principal Component Analysis (PCA) based on calculated molecular descriptors quantitatively differentiating solutes was performed in order to investigate the similarity and dissimilarity between tested compounds. The separation abilities of mobile and stationary phases were compared based on separation factor α. Chromatographic retention data and possible retention mechanisms also were discussed. (author)

  12. Biogas final digestive byproduct applied to croplands as fertilizer contains high levels of steroid hormones

    DEFF Research Database (Denmark)

    Rodriguez-Navas, Carlos; Björklund, Erland; Halling-Sørensen, Bent

    2013-01-01

    that utilize different anaerobic digestion technologies (mesophilic and thermophilic) from swine manure and other organic wastes. Individual hormone concentration levels were observed up to 1478 ng g(-1) dry weight or 22.5 mg kg(-1) N with estrone and progesterone reaching highest concentration levels....... Evaluation of the potential environmental burden through the application in agriculture was also assessed on the basis of predicted environmental concentrations. This study indicates that the biogas digestion process does not completely remove steroid hormones from livestock manure and use of final digestate......In this study we evaluate and demonstrate the occurrence of nine natural and one synthetic steroid hormone, including estrogens, androgens and progestagens in biogas final digestate byproduct (digestion liquid) commonly used as an agricultural fertilizer. We investigated two biogas sites...

  13. New perspectives on Mars and Venus: unravelling the role of androgens in gender differences in cardiovascular biology and disease.

    Science.gov (United States)

    Ng, Martin K C

    2007-06-01

    There are substantial gender differences in the pattern, severity and clinical outcomes of coronary heart disease independent of environmental risk factor exposure. As a consequence, there has been considerable interest in the potential role of sex hormones in atherogenesis, particularly the potential protective effects of oestrogen. However, the failure of the recent clinical randomised trials to show a cardioprotective effect for oestrogen coupled with a growing interest in androgen replacement therapy in elderly men has refocused interest on the role of androgens in cardiovascular biology and disease. Over the last decade, compelling evidence has emerged that sex differences in vascular biology are not only determined by gender-related differences in sex steroid levels but also by gender-specific tissue and cellular characteristics which mediate sex-specific responses to a variety of stimuli. In the vasculature, androgens often act in a gender-specific manner, with differential effects in male and female cells. This gender-dependent regulation may have important implications for understanding the basis of the gender gap in atherosclerosis and may eventually lead to the development of sex-specific treatments for cardiovascular disease. This review will summarise the current data for the role of androgens in gender differences in coronary heart disease and cardiovascular biology.

  14. Androgen levels in women with various forms of ovarian dysfunction: associations with cardiometabolic features.

    Science.gov (United States)

    Daan, N M P; Jaspers, L; Koster, M P H; Broekmans, F J M; de Rijke, Y B; Franco, O H; Laven, J S E; Kavousi, M; Fauser, B C J M

    2015-10-01

    Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition. Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes of low as well as high androgen levels have been associated with increased CVD risk in both men and women. This cross-sectional study included 680 women with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), natural post-menopausal women (NM), or regular menstrual cycles (RC) (170 women per group). Measurements of serum testosterone, androstenedione and dehydroepiandrosterone sulfate were performed using liquid chromatography-tandem mass spectrometry. Assessments were taken of body mass index (BMI), blood pressure, lipid profiles, glucose, insulin and SHBG, and the bioactive fraction of circulating testosterone was calculated using the free androgen index (FAI). PCOS women were hyperandrogenic [median FAI = 4.9 (IQR 3.6-7.4)], and POI women were hypoandrogenic [FAI = 1.2 (0.8-1.7)], compared with RC women [FAI = 1.7 (1.1-2.8)], after adjustment for age, ethnicity, smoking and BMI (P cardiometabolic features were the strongest in PCOS women, even after adjustment for BMI. Associations between androgen levels and cardiometabolic features were assessed in PCOS, POI and NM women only, due to a lack of available data in RC women. Due to the cross-sectional design of the current study, the potential associations between androgen levels and actual future cardiovascular events could not be assessed. This study affirms the potent effect of androgens on cardiometabolic features, indicating that androgens should indeed be regarded as important denominators of women's health. Future research

  15. Differential responses of brain, gonad and muscle steroid levels to changes in social status and sex in a sequential and bidirectional hermaphroditic fish.

    Directory of Open Access Journals (Sweden)

    Varenka Lorenzi

    Full Text Available Sex steroids can both modulate and be modulated by behavior, and their actions are mediated by complex interactions among multiple hormone sources and targets. While gonadal steroids delivered via circulation can affect behavior, changes in local brain steroid synthesis also can modulate behavior. The relative steroid load across different tissues and the association of these levels with rates of behavior have not been well studied. The bluebanded goby (Lythrypnus dalli is a sex changing fish in which social status determines sexual phenotype. We examined changes in steroid levels in brain, gonad and body muscle at either 24 hours or 6 days after social induction of protogynous sex change, and from individuals in stable social groups not undergoing sex change. For each tissue, we measured levels of estradiol (E(2, testosterone (T and 11-ketotestosterone (KT. Females had more T than males in the gonads, and more E(2 in all tissues but there was no sex difference in KT. For both sexes, E(2 was higher in the gonad than in other tissues while androgens were higher in the brain. During sex change, brain T levels dropped while brain KT increased, and brain E(2 levels did not change. We found a positive relationship between androgens and aggression in the most dominant females but only when the male was removed from the social group. The results demonstrate that steroid levels are responsive to changes in the social environment, and that their concentrations vary in different tissues. Also, we suggest that rapid changes in brain androgen levels might be important in inducing behavioral and/or morphological changes associated with protogynous sex change.

  16. Androgen Bioassay for the Detection of Nonlabeled Androgenic Compounds in Nutritional Supplements.

    Science.gov (United States)

    Cooper, Elliot R; McGrath, Kristine C Y; Li, XiaoHong; Heather, Alison K

    2018-01-01

    Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy, while the general population hopes to improve body image or vitality. While many supplements contain ingredients that may have useful properties, there are supplements that are contaminated with compounds that are banned for use in sport or have been deliberately adulterated to fortify a supplement with an ingredient that will produce the advertised effect. In the present study, we have used yeast cell and mammalian cell androgen bioassays to characterize the androgenic bioactivity of 112 sports supplements available from the Australian market, either over the counter or via the Internet. All 112 products did not declare an androgen on the label as an included ingredient. Our findings show that six out of 112 supplements had strong androgenic bioactivity in the yeast cell bioassay, indicating products spiked or contaminated with androgens. The mammalian cell bioassay confirmed the strong androgenic bioactivity of five out of six positive supplements. Supplement 6 was metabolized to weaker androgenic bioactivity in the mammalian cells. Further to this, Supplement 6 was positive in a yeast cell progestin bioassay. Together, these findings highlight that nutritional supplements, taken without medical supervision, could expose or predispose users to the adverse consequences of androgen abuse. The findings reinforce the need to increase awareness of the dangers of nutritional supplements and highlight the challenges that clinicians face in the fast-growing market of nutritional supplements.

  17. Disse fire typer bruger steroider

    DEFF Research Database (Denmark)

    Vinther, Anders Schmidt; Christiansen, Ask Vest

    2017-01-01

    Vi render i motionscentret som aldrig før, og ønsket om at forbedre sin krop lokker nogle ud i at bruge steroider. Brugerne kan inddeles i fire typer – fra den eksperimenterende YOLO-type til de, der gerne vil være klar til stranden.......Vi render i motionscentret som aldrig før, og ønsket om at forbedre sin krop lokker nogle ud i at bruge steroider. Brugerne kan inddeles i fire typer – fra den eksperimenterende YOLO-type til de, der gerne vil være klar til stranden....

  18. Design and synthesis of tricyclic tetrahydroquinolines as a new series of nonsteroidal selective androgen receptor modulators (SARMs).

    Science.gov (United States)

    Nagata, Naoya; Miyakawa, Motonori; Amano, Seiji; Furuya, Kazuyuki; Yamamoto, Noriko; Inoguchi, Kiyoshi

    2011-03-15

    Some tricyclic tetrahydroquinolines (THQs) were found to have the potential of a new series of nonsteroidal selective androgen receptor modulators (SARMs). Compound 5b was first designed and synthesized under our hypothesis based on a four-point pharmacophoric requirement of the 3-carbonyl, 18-methyl, 17-hydroxyl, and 13-quaternary carbon groups of dihydrotestosterone (DHT). It was revealed that this compound exhibits not only a strong androgen receptor (AR) agonistic activity (EC(50)=9.2 nM) but also the highest selectivity in binding affinity to AR among the steroid hormone receptors. Furthermore, this compound showed a weak virilizing effect with retention of the desired anabolic effect as compared with DHT in vivo. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Position stand on androgen and human growth hormone use.

    Science.gov (United States)

    Hoffman, Jay R; Kraemer, William J; Bhasin, Shalender; Storer, Thomas; Ratamess, Nicholas A; Haff, G Gregory; Willoughby, Darryn S; Rogol, Alan D

    2009-08-01

    the NSCA that through education and research we can mitigate the abuse of androgens and hGH by athletes. Due to the diversity of testosterone-related drugs and molecules, the term androgens is believed to be a more appropriate term for anabolic steroids.

  20. Renaturation of the androgen receptor after denaturation in SDS

    International Nuclear Information System (INIS)

    Johnson, M.P.; Young, C.Y.F.; Rowley, D.R.; Tindall, D.J.

    1986-01-01

    Renaturation of the steroid binding activity of receptor proteins is a potentially useful tool for their purification and analysis. Cytosol was prepared from rat Dunning prostate tumor in buffer containing molybdate and then denatured by addition of SDS buffer and heating. Aliquots were precipitated in cold acetone and the resulting pellets were washed and solubilized with a small volume of solution containing a chaotropic agent such as 6M guanidine, 8M urea, or 5M sodium iodide. After a 20-minute incubation, samples were diluted 20-fold with buffer containing 4nM [ 3 H]dihydrotestosterone with or without excess unlabeled dihydrotestosterone. Diluted samples were incubated at 0 0 C for varying periods of time prior to assay of bound radioactivity using hydroxylapatite. A time-course of renaturation after exposure to guanidine showed a steady increase of specific binding activity during the first 7 hrs post-dilution that remained stable up to 22 hrs. Experiments with guanidine consistently demonstrated that 25-50% of binding activity was recoverable. Preliminary results using urea or sodium iodide were similar. Efforts to optimize recovery and to characterize the renatured androgen receptor are in progress

  1. Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra

    Directory of Open Access Journals (Sweden)

    Purves-Tyson Tertia D

    2012-08-01

    Full Text Available Abstract Background Increased risk of schizophrenia in adolescent males indicates that a link between the development of dopamine-related psychopathology and testosterone-driven brain changes may exist. However, contradictions as to whether testosterone increases or decreases dopamine neurotransmission are found and most studies address this in adult animals. Testosterone-dependent actions in neurons are direct via activation of androgen receptors (AR or indirect by conversion to 17β-estradiol and activation of estrogen receptors (ER. How midbrain dopamine neurons respond to sex steroids depends on the presence of sex steroid receptor(s and the level of steroid conversion enzymes (aromatase and 5α-reductase. We investigated whether gonadectomy and sex steroid replacement could influence dopamine levels by changing tyrosine hydroxylase (TH protein and mRNA and/or dopamine breakdown enzyme mRNA levels [catechol-O-methyl transferase (COMT and monoamine oxygenase (MAO A and B] in the adolescent male rat substantia nigra. We hypothesized that adolescent testosterone would regulate sex steroid signaling through regulation of ER and AR mRNAs and through modulation of aromatase and 5α-reductase mRNA levels. Results We find ERα and AR in midbrain dopamine neurons in adolescent male rats, indicating that dopamine neurons are poised to respond to circulating sex steroids. We report that androgens (T and DHT increase TH protein and increase COMT, MAOA and MAOB mRNAs in the adolescent male rat substantia nigra. We report that all three sex steroids increase AR mRNA. Differential action on ER pathways, with ERα mRNA down-regulation and ERβ mRNA up-regulation by testosterone was found. 5α reductase-1 mRNA was increased by AR activation, and aromatase mRNA was decreased by gonadectomy. Conclusions We conclude that increased testosterone at adolescence can shift the balance of sex steroid signaling to favor androgenic responses through promoting

  2. Determination of steroids in manure and soil

    DEFF Research Database (Denmark)

    Hansen, Martin; Björklund, Bengt Erland; Halling-Sørensen, Bent

    A genuine analytical method to determine native steroids (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, 17b-estradiol, and 17a-estradiol) and one anthropogenic steroid (ethynylestradiol) in environmental solid samples is presented...

  3. Expression of sex steroid hormone-related genes in the embryo of the leopard gecko.

    Science.gov (United States)

    Endo, Daisuke; Kanaho, Yoh-Ichiro; Park, Min Kyun

    2008-01-01

    Sex steroid hormones are known to play a central role in vertebrate sex determination and differentiation. However, the tissues in which they are produced or received during development, especially around the period of sex determination of the gonads, have rarely been investigated. In this study, we identified the cDNA sequence, including the full-length of the coding region of cholesterol side-chain cleavage enzyme (P450scc), from the leopard gecko; a lizard with temperature-dependent sex determination. Embryonic expression analysis of two steroidogenic enzymes, P450scc and P450 aromatase (P450arom), and four sex steroid hormone receptors, androgen receptor, estrogen receptor alpha and beta, and progesterone receptor, was subsequently conducted. mRNA expression of both steroidogenic enzymes was observed in the brain and gonads prior to the temperature-sensitive period of sex determination. The mRNAs of the four sex steroid hormone receptors were also detected in the brain and gonads at all stages examined. These results suggest the existence of a gonad-independent sex steroid hormone signaling system in the developing leopard gecko brain.

  4. Ovarian steroid cell tumor in women with polycystic ovarian syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yarandi F

    2013-04-01

    Full Text Available Background: Steroid cell tumor is one of the rare ovarian tumors and forms 0.1% of all ovarian tumors, divided to three subgroups. Steroid cell tumor that are not otherwise specified (NOS are the most common type and represent 60% of steroid cell tumors. One of the most known signs of this tumor is hormonal function, especially androgenic effects of it. Primary treatment consists of eradication of tumor via surgery.Case presentation: The patient is a 29 years old female with history of poly cystic ovarian syndrome since 10 years ago, who attended to the clinic of General Women Hospital of Tehran in January 2011. In pelvic ultrasonography, there was a 6449mm mass in the right adnexa consisting of homogeneous component. She underwent laparotomy and unilateral salpingoophorectomy was done. Pathological report was steroid cell tumor of ovary.Conclusion: The aim of this study is reporting one of the rare tumors of ovary and assessment of the correct way of diagnosis and treatment of it.

  5. Biogas final digestive byproduct applied to croplands as fertilizer contains high levels of steroid hormones

    International Nuclear Information System (INIS)

    Rodriguez-Navas, Carlos; Björklund, Erland; Halling-Sørensen, Bent; Hansen, Martin

    2013-01-01

    In this study we evaluate and demonstrate the occurrence of nine natural and one synthetic steroid hormone, including estrogens, androgens and progestagens in biogas final digestate byproduct (digestion liquid) commonly used as an agricultural fertilizer. We investigated two biogas sites that utilize different anaerobic digestion technologies (mesophilic and thermophilic) from swine manure and other organic wastes. Individual hormone concentration levels were observed up to 1478 ng g −1 dry weight or 22.5 mg kg −1 N with estrone and progesterone reaching highest concentration levels. Evaluation of the potential environmental burden through the application in agriculture was also assessed on the basis of predicted environmental concentrations. This study indicates that the biogas digestion process does not completely remove steroid hormones from livestock manure and use of final digestate byproduct on croplands contributes to the environmental emission of hormones. -- Eight steroid hormones were found in biogas digestate byproduct in the ng g −1 dm levels. Anaerobic digestion processes do not completely remove steroid hormones from organic waste residues

  6. [Neurological and psychiatric aspects of some endocrine diseases. The role of neurosteroids and neuroactive steroids].

    Science.gov (United States)

    Aszalós, Zsuzsa

    2007-10-14

    Regardless of their origin, neuroactive steroids are capable of modifying neural activities by modulating different types of membrane receptors. Neurosteroids are synthesized de novo in neurones and glia. Steroidogenic enzymes are found in the central nervous system. Classical steroid receptors are localized in the cytoplasm, they exert regulatory actions on the genome, and their activation causes medium- and long-term effects. Non-classical receptors are located within the membrane and act as mediators of short-term effects. Other important players are co-repressors and co-activators that can interfere with or enhance the activity of steroid receptors. Beyond their function in stress, corticosteroids play a very important role in fear, anxiety, and memory functions. Patients with Cushing's syndrome frequently develop mood disorder, reversible brain atrophy with transient memory loss, rarely delirium or psychosis. Well-known peripheral symptom is steroidal myopathy. In patients with Addison's disease the main signs are weakness of muscles, lack of energy, decreased mental functions and reduced quality of life. Estrogen and progesterone have their own respective hormone receptors, whereas allopregnanolone acts via the GABA receptors. These hormones have significant role in the development of brain, the architecture of neural circuits and dendrites, density of axonal connections, and the number of neurons. They influence maturation, neuroprotection, seizures, cognitive functions, mood, anxiety, pain, and restitution of peripheral nerves. Androgens also affect cognitive functions, pain, anxiety, mood, and additionally aggression.

  7. Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome.

    Science.gov (United States)

    Eisenhofer, Graeme; Masjkur, Jimmy; Peitzsch, Mirko; Di Dalmazi, Guido; Bidlingmaier, Martin; Grüber, Matthias; Fazel, Julia; Osswald, Andrea; Beuschlein, Felix; Reincke, Martin

    2018-03-01

    Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes. © 2017 American Association for Clinical Chemistry.

  8. Selective androgen receptor modulators (SARMs) negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

    Science.gov (United States)

    Narayanan, Ramesh; Ahn, Sunjoo; Cheney, Misty D; Yepuru, Muralimohan; Miller, Duane D; Steiner, Mitchell S; Dalton, James T

    2014-01-01

    The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER)-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer. Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were performed to understand the mechanisms of action. Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures. 1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

  9. Selective androgen receptor modulators (SARMs negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

    Directory of Open Access Journals (Sweden)

    Ramesh Narayanan

    Full Text Available The androgen receptor (AR is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer.Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC co-culture signaling studies were performed to understand the mechanisms of action.Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures.1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

  10. Androgen receptor drives cellular senescence.

    Directory of Open Access Journals (Sweden)

    Yelena Mirochnik

    Full Text Available The accepted androgen receptor (AR role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.

  11. Recent advances in steroid radioimmunoassay

    International Nuclear Information System (INIS)

    Jeffcoate, S.L.

    1977-01-01

    The advances since 1974 in the techniques of measuring steroid molecules by radioimmunoassay are reviewed in this paper. They are considered under the following headings: preparation and use of antisera; preparation and use of tracers; preparation of biological samples before assay; dispensing of the reagents in the assay; separation of free and bound radioactivity; counting and data processing; quality control and standardization. (orig.) [de

  12. Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function.

    Directory of Open Access Journals (Sweden)

    Regina T Knapp

    Full Text Available Hsp70 binding protein 1 (HspBP1 and Bcl2-associated athanogene 1 (BAG-1, the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70 chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR, the mineralocorticoid receptor (MR, and the androgen receptor (AR. BAG-1 diversely affects steroid receptor activity, while to date the influence of HspBP1 on steroid receptor function is mostly unknown. Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes and steroid receptor activity. Coimmunoprecipitation studies indicated preferential binding of Hsp40 and the steroid receptors to BAG-1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as shown by pull-down assays. Reporter gene experiments revealed an inhibitory effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone concentrations at or approaching saturation. BAG-1M exhibited a transition from stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology.

  13. The in vitro biosynthesis of epitestosterone and testosterone from C19 steroid precursors in the testis of the lizard Tiliqua rugosa

    International Nuclear Information System (INIS)

    Huf, P.A.; Bourne, A.R.; Watson, T.G.

    1989-01-01

    The metabolism of androgens in the testis of the lizard Tiliqua rugosa has been studied in vitro by incubating cellular homogenates with radiolabeled C19-steroid substrates. The identification 17 beta-oxidoreductase and 3 beta-hydroxysteroid dehydrogenase/isomerase activities. Aromatase, 5 alpha-reductase, and 17 alpha/beta-epimerase activities were not detected. The 17 alpha-oxidoreductase activity was temperature dependent (maximal at 32 degrees), while the 17 beta-oxidoreductase activity was temperature independent. Time yield and dual-label studies indicated that testosterone biosynthesis mainly involves the 4-ene pathway (via androstenedione), whereas the formation of epitestosterone uses both the 4-ene and 5-ene (via 5-androstene-3 beta, 17 alpha-diol) pathways. The function of alternative pathways in androgen biosynthesis is discussed, as is the role of temperature in the intratesticular regulation of androgen production

  14. Androgen circle of polycystic ovary syndrome.

    Science.gov (United States)

    Homburg, Roy

    2009-07-01

    Although the aetiology of polycystic ovary syndrome (PCOS) is still not known and the search for causative genes is proving elusive, it is generally agreed that hyperandrogenism is at the heart of the syndrome. Here, it is proposed that excess androgens are the root cause of PCOS starting from their influence on the female fetus in programming gene expression, producing the characteristic signs and symptoms which are then exacerbated by a propagation of excess ovarian androgen production from multiple small follicles, anovulation and insulin resistance in the reproductive life-span, thus setting up a vicious perpetual circle of androgen excess. This opinion paper, rather than being a full-scale review, is intentionally biased in support of this hypothesis that androgen excess is the 'root of all evil' in PCOS; in the hope that its acceptance could lead to more direct treatment of the syndrome in all its facets rather than the symptomatic treatment of side effects of androgen excess that we are addressing today.

  15. Effects of sub-lethal levels of dichlorodiphenyltrichloroethane and dichlorodiphenyldichloroethylene on in vitro steroid biosynthesis by ovarian follicles or steroid metabolism by embryos of rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Petkam, Rakpong; Renaud, Rick; Lin, Lucy; Boermans, Herman; Leatherland, John

    2005-01-01

    This study examined the possibility that DDT and DDE, at sub-lethal exposure levels, exert direct effects on the biotransformation of gonadal steroids by rainbow trout (Oncorhynchus mykiss) ovarian follicles and embryos. Ovarian follicles were co-incubated with DDT or DDE at 0.01 or 1 mg l -1 to examine effects of the pesticides on basal or cAMP-activated steroidogenesis. Ovarian preparations were incubated with radiolabelled [ 3 H]pregnenolone ([ 3 H]P 5 ), and the tritiated metabolites of [ 3 H]P 5 metabolism were separated using high-performance liquid chromatography (HPLC). Testosterone (T) and 17β-estradiol (E 2 ) production were also measured using radioimmunoassay (RIA). Embryos were either exposed to the pesticides in ovo, or co-incubated in vitro with the pesticides. The effect of the pesticides on embryo steroid biotransformation was examined using a range of radioactively labelled substrates, including [ 3 H]P 5 , [ 3 H]progesterone ([ 3 H]P 4 ), [ 3 H]T and [ 3 H]E 2 . At the concentrations used, the pesticides had no significant effect on the relative amounts of unconjugated radiolabelled steroids formed by the biotransformation of [ 3 H]P 5 under conditions of basal or cAMP-stimulated ovarian steroidogenesis. However, DDT and DDE appeared to reduce the basal accumulation of androgen as a product of P 5 biotransformation by ovarian follicles. Basal or cAMP-stimulated total estrogen production was not affected. In addition, DDT at 1 mg l -1 and DDE at 0.01 mg l -1 significantly increased and decreased cAMP-stimulated T accumulation, respectively. Also DDT at 0.01 mg l -1 and DDE at 1 mg l -1 significantly increased and decreased basal E 2 accumulation, respectively. The steroid metabolites synthesized from the different substrates by embryos were essentially similar in both controls and pesticide-exposed groups, and the survival of embryos to hatch was not significantly affected by pesticide exposure, in ovo, with an approximately 90% hatchability in

  16. Effects of sub-lethal levels of dichlorodiphenyltrichloroethane and dichlorodiphenyldichloroethylene on in vitro steroid biosynthesis by ovarian follicles or steroid metabolism by embryos of rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Petkam, Rakpong [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Renaud, Rick [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Lin, Lucy [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Boermans, Herman [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Leatherland, John [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada)]. E-mail: jleather@ovc.uoguelph.ca

    2005-07-01

    This study examined the possibility that DDT and DDE, at sub-lethal exposure levels, exert direct effects on the biotransformation of gonadal steroids by rainbow trout (Oncorhynchus mykiss) ovarian follicles and embryos. Ovarian follicles were co-incubated with DDT or DDE at 0.01 or 1 mg l{sup -1} to examine effects of the pesticides on basal or cAMP-activated steroidogenesis. Ovarian preparations were incubated with radiolabelled [{sup 3}H]pregnenolone ([{sup 3}H]P{sub 5}), and the tritiated metabolites of [{sup 3}H]P{sub 5} metabolism were separated using high-performance liquid chromatography (HPLC). Testosterone (T) and 17{beta}-estradiol (E{sub 2}) production were also measured using radioimmunoassay (RIA). Embryos were either exposed to the pesticides in ovo, or co-incubated in vitro with the pesticides. The effect of the pesticides on embryo steroid biotransformation was examined using a range of radioactively labelled substrates, including [{sup 3}H]P{sub 5}, [{sup 3}H]progesterone ([{sup 3}H]P{sub 4}), [{sup 3}H]T and [{sup 3}H]E{sub 2}. At the concentrations used, the pesticides had no significant effect on the relative amounts of unconjugated radiolabelled steroids formed by the biotransformation of [{sup 3}H]P{sub 5} under conditions of basal or cAMP-stimulated ovarian steroidogenesis. However, DDT and DDE appeared to reduce the basal accumulation of androgen as a product of P{sub 5} biotransformation by ovarian follicles. Basal or cAMP-stimulated total estrogen production was not affected. In addition, DDT at 1 mg l{sup -1} and DDE at 0.01 mg l{sup -1} significantly increased and decreased cAMP-stimulated T accumulation, respectively. Also DDT at 0.01 mg l{sup -1} and DDE at 1 mg l{sup -1} significantly increased and decreased basal E{sub 2} accumulation, respectively. The steroid metabolites synthesized from the different substrates by embryos were essentially similar in both controls and pesticide-exposed groups, and the survival of embryos to hatch

  17. Liver pathology associated with the use of anabolic-androgenic steroids

    DEFF Research Database (Denmark)

    Søe, Katrine; Søe, Martin Jensen; Gluud, C

    1992-01-01

    that AAS can cause development of hepatocellular carcinomas when used in the usual therapeutic doses. Tumours reported as hepatocellular carcinomas caused by AAS seems to be hyperplastic lesions of a benign nature able to regress with withdrawal of the putative agent. The effects of untraditional...

  18. Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation

    DEFF Research Database (Denmark)

    Rasmussen, Jon Jarløv; Selmer, Christian; Østergren, Peter Busch

    2016-01-01

    training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. RESULTS: Former AAS abusers...... exhibited significantly lower median (25th -75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7) nmol/l vs. 18.8 (16.6-22.0) nmol/l) (P testosterone levels below...... the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P

  19. Androgen-like activities in blood cleared for endogenous steroid hormones across European and Inuit populations

    DEFF Research Database (Denmark)

    Krüger, Tanja; Hjelmborg, Philip Sebastian; Goralczyk, Katarzyna

    Human exposure to environmental contaminants is ubiquitous and can affect individuals living close to as well as remote from the sources of contaminants. All individuals carry a burden of the lipophilic persistent organic pollutants (POPs) and heavy metals in their body. POPs includes polychlorin...

  20. Cosmetic doping--when anabolic-androgenic steroids are not enough.

    Science.gov (United States)

    Figueiredo, Vandré Casagrande; Silva, Paulo Rodrigo Pedroso da

    2014-07-01

    Doping is considered to be a major sports problem. This article describes a new threat and challenge to the sport of bodybuilding; the nonmedical use of a chemical in order to mimic muscle hypertrophy. Although muscle fillers are not new, being used for cosmetic purposes in medicine for a long time, the illegal use of muscle fillers has been increasing during the last few years and decades. The history of cosmetic doping, with particular attention to the Brazilian case, is discussed. Limitations are noted and future needed research is suggested.

  1. Androgens as therapy for androgen receptor-positive castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Lin Hui-Ping

    2011-08-01

    Full Text Available Abstract Prostate cancer is the most frequently diagnosed non-cutaneous tumor of men in Western countries. While surgery is often successful for organ-confined prostate cancer, androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. Shortening the period of androgen ablation therapy may benefit prostate cancer patients. Intermittent Androgen Deprivation therapy improves quality of life, reduces toxicity and medical costs, and delays disease progression in some patients. Cell culture and xenograft studies using androgen receptor (AR-positive castration-resistant human prostate cancers cells (LNCaP, ARCaP, and PC-3 cells over-expressing AR suggest that androgens may suppress the growth of AR-rich prostate cancer cells. Androgens cause growth inhibition and G1 cell cycle arrest in these cells by regulating c-Myc, Skp2, and p27Kip via AR. Higher dosages of testosterone cause greater growth inhibition of relapsed tumors. Manipulating androgen/AR signaling may therefore be a potential therapy for AR-positive advanced prostate cancer.

  2. Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

    National Research Council Canada - National Science Library

    Wiren, Kristine M; Jepsen, Karl

    2006-01-01

    .... We genetically engineered transgenic mice in which androgen receptor (AR) overexpression is skeletally targeted in two separate models to better understand the role of androgen signaling directly in bone...

  3. Three novel and two known androgen receptor gene mutations ...

    Indian Academy of Sciences (India)

    gene mutations associated with androgen insensitivity syndrome in sex-reversed XY female patients. J. Genet. ... signal and a C-terminal. Keywords. androgen insensitivity syndrome; androgen receptor; truncation mutation; N-terminal domain; XY sex reversal. .... and an increased risk of gonadal tumour. Mutations in SRY.

  4. Cholestatic Jaundice With the Use of Methylstenbolone and Dymethazine, Designer Steroids Found in Super DMZ Rx 2.0 “Nutritional Supplement”

    Directory of Open Access Journals (Sweden)

    Priscilla Agbenyefia BA

    2014-04-01

    Full Text Available “Nutritional supplements” that promise an increase in muscle mass and strength are becoming a go to item as enhancing one’s physical appearance becomes a more important part of our society. This is alarming because many of these nutritional supplements rely on androgen precursors to deliver their promises, without adequately informing consumers of the potential side effects of such agents. These products may conceal the presence of potent androgens to avoid regulatory sanctions and become more appealing to consumers. Recent reports have shown that some products marketed as “nutritional supplements” have been found to contain androgenic anabolic steroids. Methylstenbolone and dymethazine are new androgenic anabolic steroids currently gaining popularity among body builders for their performance-enhancing properties and rapid effects on muscle mass. These agents are found together in Super DMZ Rx 2.0, a “dietary supplement” for bodybuilders. Here we report the first case of Super DMZ Rx 2.0–induced cholestatic jaundice in a 26-year-old previously healthy Caucasian male, who took the supplement according to the manufacturer’s instructions for 30 days.

  5. Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia

    Directory of Open Access Journals (Sweden)

    Sung Won Lee

    2015-06-01

    Full Text Available Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

  6. Male sexual polymorphism, alternative reproductive tactics, and androgens in combtooth blennies (pisces: blenniidae).

    Science.gov (United States)

    Oliveira, R F; Canario, A V; Grober, M S

    2001-09-01

    In species in which intense intermale competition for the access to females is present males of lower competitive ability may adopt alternative reproductive tactics (ART) to get access to mates. These ART translate in many cases into male sexual polymorphism, with individuals following distinctly different tactics. Usually two alternative male morphs can be recognized in species with ART: (1) bourgeois males that compete for access to mates invest in typically male behaviors, such as building elaborated nests or displaying ornaments; and (2) parasitic males that take advantage of the success of the bourgeois males in attracting females and attempt "sneaker" fertilizations (e.g., sneaker and satellite males). In combtooth blennies (Blenniidae) the co-occurrence of ART and male sexual polymorphism has been described for two temperate species: the peacock blenny, Salaria pavo, and the Azorean rock-pool blenny, Parablennius sanguinolentus parvicornis. Interestingly, while in the peacock blenny the alternative male morph adopts a sneaker tactic, in the rock-pool blenny parasitic males act as satellites to nest-holder males. Thus, this variation in the ART expressed in these two closely related species allows for a comparative study of the proximate and ultimate factors affecting the expression of the two ART. In this article we summarize the available information on androgen levels in bourgeois and parasitic males of natural populations of the two species and of recent studies on the effect of exogenous administration of androgens on tactic switching in parasitic males of the two species. The information is discussed within the frame of the relative plasticity hypothesis, which predicts that plastic alternative morphs should show differences in hormone levels and that the administration of sex steroids should be effective in promoting the switch from the parasitic to bourgeois tactic. The evidence is only partly consistent with this hypothesis. Alternatively, a social

  7. Sex steroid receptor expression in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Mehrad, Mitra; Trejo Bittar, Humberto E; Yousem, Samuel A

    2017-08-01

    Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    OpenAIRE

    Chadha, D.; Pache, T.D.; Huikeshoven, Frans; Brinkmann, Albert; Kwast, Theo

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycy...

  9. Pharmacodynamics of selective androgen receptor modulators.

    Science.gov (United States)

    Yin, Donghua; Gao, Wenqing; Kearbey, Jeffrey D; Xu, Huiping; Chung, Kiwon; He, Yali; Marhefka, Craig A; Veverka, Karen A; Miller, Duane D; Dalton, James T

    2003-03-01

    The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

  10. Developmental Programming: Impact of Prenatal Testosterone Excess on Steroidal Machinery and Cell Differentiation Markers in Visceral Adipocytes of Female Sheep.

    Science.gov (United States)

    Puttabyatappa, Muraly; Lu, Chunxia; Martin, Jacob D; Chazenbalk, Gregorio; Dumesic, Daniel; Padmanabhan, Vasantha

    2017-01-01

    Prenatal testosterone (T)-treated female sheep manifest reduced adipocyte size and peripheral insulin resistance. The small adipocyte phenotype may reflect defects in adipogenesis and its steroidal machinery. To test whether prenatal T treatment from gestational days 30 to 90 alters the visceral adipose tissue (VAT) steroidal machinery and reduces adipocyte differentiation, we examined expression of the steroidogenic enzymes, steroid receptors, and adipocyte differentiation markers at fetal day 90 and postnatal ages 10 and 21 months. Because gestational T treatment increases fetal T and maternal insulin, the contributions of these were assessed by androgen receptor antagonist or insulin sensitizer cotreatment, either separately (at fetal day 90 and 21 months of age time points) or together (10 months of age). The effects on adipogenesis were assessed in the VAT-derived mesenchymal stem cells (AT-MSCs) from pre- and postpubertal time points to evaluate the effects of pubertal steroidal changes on adipogenesis. Our results show that VAT manifests potentially a predominant estrogenic intracrine milieu (increased aromatase and estrogen receptor α) and reduced differentiation markers at fetal day 90 and postnatal 21 months of age. These changes appear to involve both androgenic and metabolic pathways. Preliminary findings suggest that prenatal T treatment reduces adipogenesis, decreases expression of differentiation, and increases expression of commitment markers at both pre- and postpubertal time points. Together, these findings suggest that (1) increased commitment of AT-MSCs to adipocyte lineage and decreased differentiation to adipocytes may underlie the small adipocyte phenotype of prenatal T-treated females and (2) excess T-induced changes in steroidal machinery in the VAT likely participate in the programming/maintenance of this defect.

  11. Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology.

    Science.gov (United States)

    Melcangi, Roberto Cosimo; Caruso, Donatella; Abbiati, Federico; Giatti, Silvia; Calabrese, Donato; Piazza, Fabrizio; Cavaletti, Guido

    2013-10-01

    Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation. A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology. The levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls. Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls. At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17β-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5α-androstane-3α,17β-diol and 17β-estradiol were observed in

  12. Short-term exposure to the organotin compound triphenyltin modulates esterified steroid levels in females of Marisa cornuarietis.

    Science.gov (United States)

    Lyssimachou, Angeliki; Bachmann, J; Porte, C

    2008-08-29

    Long-term exposures to organotin compounds have shown alterations on endogenous steroid levels in gastropods together with the development of imposex. However, information regarding short-term effects of these compounds on the endocrine system of gastropods is lacking. This work aimed at investigating those responses in the ramshorn snail Marisa cornuarietis by looking at both endogenous levels of free and esterified steroids and the metabolism of the androgen precursor androstenedione by digestive gland/gonad microsomal fractions. One-week exposure to the organotin compound triphenyltin (TPT) led to a significant increase in esterified testosterone (60-85%) and a decrease in esterified estradiol (50-84%) in females, but had no effect on males. The observed alterations in esterified steroids were not directly related to changes in P450 aromatase activity that remained unchanged in exposed females. The enzymes involved in the metabolism of the androgen precursor androstenedione, namely 17beta-hydroxysteroid dehydrogenases and 5alpha-reductases, were not significantly altered by TPT exposure, suggesting that such enzymes are not primary targets of TPT in M. cornuarietis. Additional studies are needed to fully understand the significance of the observed alterations in females and their potential relationship with the development of imposex.

  13. Regulation of expression of Na+,K+-ATPase in androgen-dependent and androgen-independent prostate cancer

    NARCIS (Netherlands)

    L.J. Blok (Leen); G.T.G. Chang; M. Steenbeek-Slotboom (M.); W.M. van Weerden (Wytske); H.G. Swarts; J.J.H.H.M. de Pont (J. J H H M); G.J. van Steenbrugge (Gert Jan); A.O. Brinkmann (Albert)

    1999-01-01

    textabstractThe β1-subunit of Na+,K+-ATPase was isolated and identified as an androgen down-regulated gene. Expression was observed at high levels in androgen-independent as compared to androgen-dependent (responsive) human prostate cancer cell lines and xenografts when grown in the presence of

  14. Sites of production of sex steroids: secretion of steroids from x-irradiated and polycystic ovaries of rats

    International Nuclear Information System (INIS)

    Sawada, T.; Ichikawa, S.

    1978-01-01

    Ovaries of immature rats and PMS-induced pregnant rats were unilaterally x-irradiated. Ten days later, the concentrations of pregnane compounds in the ovarian venous plasma were measured. LH (2 μg) was injected iv 30 min before bleeding. A comparison of steroid levels in the ovarian venous effluent of rats with and without destruction of selected tissue components by irradiation of the ovaries suggests that the follicles contribute to the secretion of 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one in the presence of interstitial gland tissue. Because it is known that follicular tissue is involved in the production of estrogens, we studied the interrelationship between the secretion of the two progesterone metabolites and estrogens in follicular polycystic ovaries of androgen-sterilized rats. Normal ovaries of diestrus-2 rats were used as controls for the polycystic ovaries. The injection of LH greatly increased the secretion of 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one within 1 h in normal ovaries, but the response of polycystic ovaries was low, suggesting low 5α-reductase activity in the cystic ovary. The polycystic ovaries exhibited a marked increase in the secretion of estrogens in response to LH, whereas normal ovaries showed no significant change. These results suggest that low 5α-reductase activity may be causally related to the high level of estrogen secretion in polycystic ovaries of androgen-sterilized rats

  15. Comparison of steroid pulse therapy and conventional oral steroid therapy as initial treatment for autoimmune pancreatitis

    International Nuclear Information System (INIS)

    Tomiyama, Takashi; Uchida, Kazushige; Matsushita, Mitsunobu; Ikeura, Tsukasa; Fukui, Toshiro; Takaoka, Makoto; Nishio, Akiyoshi; Okazaki, Kazuichi

    2011-01-01

    The efficacy of oral steroid therapy for autoimmune pancreatitis (AIP) is well known, and oral prednisolone treatment is most usually commenced at 30-40 mg/day, but there have been few reports about comparative studies of oral steroid therapy and steroid pulse therapy as the initial treatment for AIP. We studied the clinical course and image findings to estimate the utility of steroid pulse therapy for AIP, comparing it with oral steroid therapy. Laboratory and image findings were assessed retrospectively in 11 patients who received steroid pulse therapy, and the findings were compared to those in 10 patients who received conventional oral steroid therapy. Change in pancreatic size showed no significant difference between the therapies after 2 weeks of treatment. Significant improvement of lower bile duct strictures after 2 weeks of treatment and that of immunoglobulin values within 6 months were shown with both therapies. However, steroid pulse therapy showed significant improvement of γ-guanosine triphosphate (GTP) in 2 weeks and of alanine aminotransferase (ALT) in 2 and 8 weeks, compared with oral steroid therapy. Moreover, there was one patient in whom the lower bile duct stricture was not improved by oral steroid therapy, but it did show improvement with steroid pulse therapy. Initial steroid pulse therapy is a beneficial alternative to oral steroid therapy for the improvement of bile duct lesions. In future, the accumulation of a larger number of patients receiving steroid pulse therapy is needed, and prospective studies will be required. (author)

  16. Role of Androgen Receptor in Growth of Androgen Independent Prostate Cancer

    National Research Council Canada - National Science Library

    Chen, Charlie

    2003-01-01

    ...) overexpression is the only consistent change in the progression of prostate cancer. In the last grand period, I confirmed by western blot analysis that androgen receptor protein is higher in HR than HS tumors...

  17. PTTG1, A novel androgen responsive gene is required for androgen-induced prostate cancer cell growth and invasion

    International Nuclear Information System (INIS)

    Zhang, Zheng; Jin, Bo; Jin, Yaqiong; Huang, Shengquan; Niu, Xiaohua; Mao, Zebin; Xin, Dianqi

    2017-01-01

    Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex. Bioinformatics analysis and experiments using PTTG1 promoter deletion mutants showed that the PTTG1 promoter contains a putative androgen response element (ARE), which localizes in the −851 to −836 region of the promoter. Androgen activated androgen receptor (AR) binding to this ARE was confirmed by Chromatin immunoprecipitation (ChIP) assay. Furthermore, Knockdown of PTTG1 expression using short hairpin RNA significantly reduced androgen-induced LNCaP cell growth and invasion. In addition, we showed PTTG1 is highly expressed in metastasis prostate cancer tissue. These results suggest that PTTG1 is a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis. - Highlights: • Androgen treatment of LNCaP cells induced PTTG1 expression. • Knockdown of PTTG1 expression significantly reduced androgen-induced LNCaP cell growth and invasion. • PTTG1 is highly expressed in metastasis prostate cancer tissue. • PTTG1 is a novel downstream target gene of androgen receptor.

  18. The Role of Androgen Excess in Metabolic Dysfunction in Women : Androgen Excess and Female Metabolic Dysfunction.

    Science.gov (United States)

    Escobar-Morreale, Héctor F

    2017-01-01

    Polycystic ovary syndrome (PCOS) is characterized by the association of androgen excess with chronic oligoovulation and/or polycystic ovarian morphology, yet metabolic disorders and classic and nonclassic cardiovascular risk factors cluster in these women from very early in life. This chapter focuses on the mechanisms underlying the association of PCOS with metabolic dysfunction, focusing on the role of androgen excess on the development of visceral adiposity and adipose tissue dysfunction.

  19. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival

    Directory of Open Access Journals (Sweden)

    Day Wanda V

    2005-04-01

    Full Text Available Abstract Background Androgens and androgen receptors (AR regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH and prostate cancer (PCa. Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA. This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. Results The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. Conclusion We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.

  20. Effects of androgen on immunohistochemical localization of androgen receptor and Connexin 43 in mouse ovary.

    Science.gov (United States)

    Yang, Mei; Li, Jianhua; An, Yulin; Zhang, Shuiwen

    2015-10-01

    Androgens have essential roles in the regulation of follicular development and female fertility. Androgen excess is the leading defect in polycystic ovary syndrome (PCOS) patients and involved in the ovarian dysfunction. The aim of this study was to elucidate the regarding regulatory role of androgen in the follicular development of female mouse. Immunohistochemical staining and Western blot analyses were performed to detect androgen receptor (AR) and Connexin 43 (Cx43) expression in ovaries from both control and testosterone-treated group mice. In this study, localizations of AR and Cx43 were dramatically altered in testosterone-treated mouse ovaries. In addition, AR expression was significantly increased, whereas Cx43 expression was markedly decreased after testosterone treatment. Alterations of AR and Cx43 expression by testosterone with concomitant reduction of MII oocytes. Overall, these results suggest the involvement of androgen in the regulation of AR and Cx43 localizations in mouse ovary. Alterations of AR and Cx43 expression by testosterone may affect normal folliculogenesis. Together these findings will enable us to begin understanding the important roles of AR and Cx43 actions in the regulation of follicular development, as well as providing insights into the role of AR and Cx43 actions in the androgen-associated reproductive diseases such as PCOS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers.

    Science.gov (United States)

    Vehof, Jelle; Hysi, Pirro G; Hammond, Christopher J

    2017-04-01

    To test the association between serum metabolites and dry eye disease (DED) using a hypothesis-free metabolomics approach. Cross-sectional association study. A total of 2819 subjects from the population-representative TwinsUK cohort in the United Kingdom, with a mean age of 57 years (range, 17-82 years). We tested associations between 222 known serum metabolites and DED. All subjects underwent nontargeted metabolomic analysis of plasma samples using gas and liquid chromatography in combination with mass spectrometry (Metabolon Inc., Durham, NC). Dry eye disease was defined from the validated Short Questionnaire for Dry Eye Syndrome (SQDES) as a previous diagnosis of DED by a clinician or "often" or "constant" symptoms of dryness and irritation. Analyses were performed with linear mixed effect models that included age, BMI, and sex as covariates, corrected for multiple testing. Primary outcome was DED as defined by the SQDES, and secondary outcomes were symptom score of DED and a clinical diagnosis of DED. Prevalence of DED as defined by the SQDES was 15.5% (n = 436). A strong and metabolome-wide significant association with DED was found with decreased levels of the metabolites androsterone sulfate (P = 0.00030) and epiandrosterone sulfate (P = 0.00036). Three other metabolites involved in androgen metabolism, 4-androsten-3beta,17beta-diol disulfate 1 and 2, and dehydroepiandrosterone sulfate, were the next most strongly associated of the 222 metabolites, but did not reach metabolome-wide significance. Dryness and irritation symptoms, as opposed to a clinical diagnosis, were particularly strongly associated with decreased androgen steroid metabolites, with all reaching metabolome-wide significance (androsterone sulfate, P = 0.000000029; epiandrosterone sulfate, P = 0.0000040; 4-androsten-3beta,17beta-diol disulfate 1, P = 0.000016; 4-androsten-3beta,17beta-diol disulfate 2, P = 0.000064; and dehydroepiandrosterone sulfate, P = 0.00011). Of these 5

  2. In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study

    International Nuclear Information System (INIS)

    Khayum, M.A.; Doorduin, J.; Antunes, I.F.; Kwizera, C.; Zijlma, R.; Boer, J.A. den; Dierckx, R.A.J.O.; Vries, E.F.J. de

    2015-01-01

    Introduction: Steroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[ 18 F]fluoro-5α-dihydrotestosterone ([ 18 F]FDHT) to image AR expression in the brain. Methods: Male Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [ 18 F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1 mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution. Results: PET imaging and ex vivo biodistribution studies showed low [ 18 F]FDHT uptake in all brain regions, except pituitary. [ 18 F]FDHT uptake in the surrounding cranial bones was high and increased over time. [ 18 F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [ 18 F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone. Conclusion: The results of this study indicate that imaging of AR availability in rat brain with [ 18 F]FDHT PET is not feasible. The low AR expression in the brain, the

  3. Sexual behavior reduces hypothalamic androgen receptor immunoreactivity

    NARCIS (Netherlands)

    Fernandez-Guasti, Alonso; Swaab, Dick; Rodríguez-Manzo, Gabriela

    2003-01-01

    Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express

  4. Therapeutic Use of Androgens in Women

    Science.gov (United States)

    ... in men, the same is not true for women. Media stories about how testosterone increases libido (sexual desire) ... medications, do have lower androgen levels than healthy women. In addition, despite claims in the popular media that getting testosterone levels checked is “a small ...

  5. The relationship between follicular fluid androgen concentrations ...

    African Journals Online (AJOL)

    Polycystic ovary syndrome (PCOS) is the most common cause of oligoanovulation, infertility, and hyperandrogenism in women and characterized by abnormal folliculogenesis. The androgen receptoe ( AR) is present in the ovary in almost all stages of folliculogenesis and has been suggested to play a proliferative role for ...

  6. Environmental concentrations of an androgenic progestin disrupts the seasonal breeding cycle in male three-spined stickleback (Gasterosteus aculeatus).

    Science.gov (United States)

    Svensson, Johan; Fick, Jerker; Brandt, Ingvar; Brunström, Björn

    2014-02-01

    Synthetic steroid hormones from contraceptive pharmaceuticals have become global aquatic contaminants. Progestins, the synthetic analogs to progesterone, are receiving increasing attention as contaminants and have been shown to impair reproduction in fish and amphibians at low ng L(-1) concentrations. Certain progestins, such as levonorgestrel have androgenic properties and seem to be several orders of magnitude more potent in terms of reproductive impairment in fish than non-androgenic progestins and progestagens. We recently reported that levonorgestrel has strong androgenic effects in female three-spined sticklebacks (Gasterosteus aculeatus), including induction of the normally male-specific glue protein spiggin and suppression of vitellogenesis. In light of this we investigated if exposure to levonorgestrel could disrupt the highly androgen-dependent seasonal reproductive cycle in male sticklebacks. Male sticklebacks that were in the final stage of a breeding period were exposed to various concentrations of levonorgestrel for six weeks in winter conditions in terms of light and temperature, after which reproductive status was evaluated from gross morphology, histology and key gene transcript levels. During the experimental period the controls had transitioned from full breeding condition into the non-breeding state, including regression of secondary sex characteristics, cessation of spiggin production in the kidney, and resumption of spermatogenesis in the testes. This is ascribed to the natural drop in plasma androgen levels after breeding. However, in the groups concurrently exposed to levonorgestrel, transition to the non-breeding condition was dose-dependently inhibited. Our results show that levonorgestrel can disrupt the seasonal breeding cycle in male sticklebacks. The fitness costs of such an effect could be detrimental to natural stickleback populations. Some effects occurred at a levonorgestrel concentration of 6.5 ng L(-1), well within the range of

  7. Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

    Science.gov (United States)

    Jedel, Elizabeth; Gustafson, Deborah; Waern, Margda; Sverrisdottir, Yrsa Bergmann; Landén, Mikael; Janson, Per Olof; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2011-11-01

    Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Peripheral conversion and uptake of androgens in a XXY-man with Klinefelter's syndrome

    International Nuclear Information System (INIS)

    Sulcova, J.; Jirasek, J.E.; Neuwirth, J.; Raboch, J.; Starka, L.

    1978-01-01

    The conversion of 3 H-testosterone and the uptake of 3 H-testosterone and 3 H-5α-dihydrotestosterone were investigated in pubic skin and pubic hair follicles of a XXY-man with inadequate pubic hair. The uptake of both androgens was demonstrated in the skin as well as in the hair follicles. Similarly the activity of steroid 5α-reductase was present in both tissues. The total conversion of 3 H-testosterone was 2-3 times higher in the patient than in control persons. In the XXY-man the major metabolites were 5α- and 5β-androstanediols, whereas in the normal men 5α-dihydrotestosterone and 4-androstenedione were mainly formed from testosterone. An explanation of the inadequate growth of pubic hair in our patient seems to be related to a conversion of testosterone - at its low plasma level - to its relatively inactive metabolites. (author)

  9. Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity

    International Nuclear Information System (INIS)

    Lubahn, D.B.; Simental, J.A.; Higgs, H.N.; Wilson, E.M.; French, F.S.; Brown, T.R.; Migeon, C.J.

    1989-01-01

    Androgens act through a receptor protein (AR) to mediate sex differentiation and development of the male phenotype. The authors have isolated the eight exons in the amino acid coding region of the AR gene from a human X chromosome library. Nucleotide sequences of the AR gene intron/exon boundaries were determined for use in designing synthetic oligonucleotide primers to bracket coding exons for amplification by the polymerase chain reaction. Genomic DNA was amplified from 46, XY phenotypic female siblings with complete androgen insensitivity syndrome. AR binding affinity for dihydrotestosterone in the affected siblings was lower than in normal males, but the binding capacity was normal. Sequence analysis of amplified exons demonstrated within the AR steroid-binding domain (exon G) a single guanine to adenine mutation, resulting in replacement of valine with methionine at amino acid residue 866. As expected, the carrier mother had both normal and mutant AR genes. Thus, a single point mutation in the steroid-binding domain of the AR gene correlated with the expression of an AR protein ineffective in stimulating male sexual development

  10. The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men.

    Science.gov (United States)

    Neychev, V K; Mitev, V I

    2005-10-03

    The aim of the current study is to investigate the influence of Tribulus terrestris extract on androgen metabolism in young males. Twenty-one healthy young 20-36 years old men with body weight ranging from 60 to 125 kg were randomly separated into three groups-two experimental (each n=7) and a control (placebo) one (n=7). The experimental groups were named TT1 and TT2 and the subjects were assigned to consume 20 and 10 mg/kg body weight per day of Tribulus terrestris extract, respectively, separated into three daily intakes for 4 weeks. Testosterone, androstenedione and luteinizing hormone levels in the serum were measured 24 h before supplementation (clear probe), and at 24, 72, 240, 408 and 576 h from the beginning of the supplementation. There was no significant difference between Tribulus terrestris supplemented groups and controls in the serum testosterone (TT1 (mean+/-S.D.: 15.75+/-1.75 nmol/l); TT2 (mean+/-S.D.: 16.32+/-1.57 nmol/l); controls (mean+/-S.D.: 17.74+/-1.09 nmol/l) (p>0.05)), androstenedione (TT1 (mean+/-S.D.: 1.927+/-0.126 ng/ml); TT2 (mean+/-S.D.: 2.026+/-0.256 ng/ml); controls (mean+/-S.D.: 1.952+/-0.236 ng/ml) (p>0.05)) or luteinizing hormone (TT1 (mean+/-S.D.: 4.662+/-0.274U/l); TT2 (mean+/-S.D.: 4.103+/-0.869U/l); controls (mean+/-S.D.: 4.170+/-0.406U/l) (p>0.05)) levels. All results were within the normal range. The findings in the current study anticipate that Tribulus terrestris steroid saponins possess neither direct nor indirect androgen-increasing properties. The study will be extended in the clarifying the probable mode of action of Tribulus terrestris steroid saponins.

  11. Identification of the molecular switch that regulates access of 5alpha-DHT to the androgen receptor.

    Science.gov (United States)

    Penning, Trevor M; Bauman, David R; Jin, Yi; Rizner, Tea Lanisik

    2007-02-01

    Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid receptors in target tissues and act as molecular switches. By acting as reductases or oxidases, HSDs convert potent ligands into their cognate inactive metabolites or vice versa. This pre-receptor regulation of steroid hormone action may have profound effects on hormonal response. We have identified the HSDs responsible for regulating ligand access to the androgen receptor (AR) in human prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha-androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short-chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha-androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase (AKRs) and SDRs function as reductases and oxidases, respectively, to control ligand access to nuclear receptors.

  12. Analytical method for the determination of trace levels of steroid hormones and corticosteroids in soil, based on PLE/SPE/LC-MS/MS.

    Science.gov (United States)

    Gineys, N; Giroud, B; Vulliet, E

    2010-07-01

    The aim of this study was to develop an efficient, sensitive and reliable analytical method for the determination of traces of steroid hormones (including oestrogen, androgens and progestagens) and corticosteroids in soil. A method of sample preparation involving pressurized liquid extraction (PLE) and solid-phase extraction (SPE) was developed for the determination of six steroids and five corticosteroids in soils, followed by analysis by liquid chromatography-tandem mass spectrometry. The conditions employed for PLE involved acetone/methanol (50:50) as the extracting solvent, a temperature of 80 degrees C, two cycles and a static time of 5 min. The extraction was followed by a SPE clean-up based on a polymeric phase. With use of protocol,