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Sample records for androgenic steroids alters

  1. 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...

  2. ANABOLIC ANDROGENIC STEROIDS AND DEPENDENCE

    Directory of Open Access Journals (Sweden)

    IHSAN SARI

    2010-12-01

    Full Text Available Anabolic androgenic steroids are used for sportive, cosmetic, therapeutic and occupational reasons and there are many side effects reported (George, 2005; Nieminen et al., 1996; O'Sullivan et al., 2000. Prevalence of anabolic steroids’ use also indicates the importance of this topic. Moreover, it is now known that use of anabolic steroids could lead to dependence which could be psychological or/and physiological (Copeland et al., 2000. It isimportant to know about all aspects of anabolic steroids including dependence. Therefore, this study has attempted to give an insight into use of anabolic steroids and dependence. The discussion will focus on prevalence, reasons, and side effects of use and physiological and psychological dependence

  3. ABUSE OF ANABOLIC ANDROGENIC STEROIDS

    OpenAIRE

    Abbas Yavari

    2009-01-01

    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 and widespread 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, ...

  4. Steroid androgen 17α-methyltestosterone induces malformations and biochemical alterations in zebrafish embryos.

    Science.gov (United States)

    Rivero-Wendt, Carla Letícia Gediel; Oliveira, Rhaul; Monteiro, Marta Sofia; Domingues, Inês; Soares, Amadeu Mortágua Velho Maia; Grisolia, Cesar Koppe

    2016-06-01

    The synthetic androgen 17α-methyltestosterone is widely used in fish aquaculture for sex reversion of female individuals. Little is known about the amount of MT residues reaching the aquatic environment and further impacts in non-target organisms, including fish early-life stages. Thus, in this work, zebrafish embryos were exposed to two forms of 17α-methyltestosterone: the pure compound (MT) and a formulation commonly used in Brazil (cMT). For MT, a 96h-LC50 of 10.09mg/l was calculated. MT also affected embryo development inducing tail malformations, edemas, abnormal development of the head, and hatching delay. At biochemical level MT inhibited vitellogenin (VTG) and inhibited cholinesterase and lactate dehydrogenase. cMT elicited similar patterns of toxicity as the pure compound (MT). Effects reported in this study suggest a potential environmental risk of MT, especially since the VTG effects occurred at environmental relevant concentrations (0.004mg/l). PMID:27137108

  5. 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.

  6. 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....

  7. Leverpatologi associeret med anaboliske-androgene steroider

    DEFF Research Database (Denmark)

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

    1994-01-01

    This review regards the liver damaging side-effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved...

  8. Using Anabolic Androgenic Steroids in Sport

    Directory of Open Access Journals (Sweden)

    Sefa Lök

    2010-12-01

    Full Text Available It is known that sportsmen especially youngers who engaged in athletism, weight lifting and body building sport have beenusing ‘‘Anabolic Androgenic Steroid’’ (AAS intensively for purpose of doping during world sport history. Used dopingsubstances to increase sport performance differ from sport branches. In some sport branches, it is used to diminish neuralstress while in other sport branches it is used to increase force, endurance and resistance against exhaustion. Today amongsportsmen using ergogenic substances to increase rivalry and physical performance for purpose of doping are increased. Inthis study using anabolic androgenic steroids in sports will be assessed.

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

    OpenAIRE

    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 volunta...

  10. 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).

  11. 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....

  12. 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)

  13. Anabolic androgenic steroid-induced hepatotoxicity.

    Science.gov (United States)

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor. PMID:27372877

  14. Anabolic androgenic steroid-induced hepatotoxicity.

    Science.gov (United States)

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor.

  15. 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.

  16. 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....

  17. Illicit anabolic-androgenic steroid use.

    Science.gov (United States)

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

    2010-06-01

    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

  18. Modulation of the cytosolic androgen receptor in striated muscle by sex steroids

    Science.gov (United States)

    Rance, N. E.; Max, S. E.

    1982-01-01

    The influence of orchiectomy (GDX) and steroid administration on the level of the cytosolic androgen receptor in the rat levator ani muscle and in rat skeletal muscles (tibialis anterior and extensor digitorum longus) was studied. Androgen receptor binding to muscle cytosol was measured using H-3 methyltrienolone (R1881) as ligand, 100 fold molar excess unlabeled R1881 to assess nonspecific binding, and 500 fold molar excess of triamcinolone acetonide to prevent binding to glucocorticoid and progestin receptors. Results demonstrate that modification of the levels of sex steroids can alter the content of androgen receptors of rat striated muscle. Data suggest that: (1) cytosolic androgen receptor levels increase after orchiectomy in both levator ani muscle and skeletal muscle; (2) the acute increase in receptor levels is blocked by an inhibitor of protein synthesis; and (3) administration of estradiol-17 beta to castrated animals increases receptor binding in levator ani muscle but not in skeletal muscle.

  19. 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…

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

    OpenAIRE

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

    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-ba...

  1. 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

  2. Anabolic androgenic steroids and violence : a medicolegal and experimental study

    OpenAIRE

    Thiblin, Ingemar

    1999-01-01

    Non-medical use of anabolic androgenic steroids (AAS) has been linked to various psychological and behavioural complications in case and survey reports. Judging from these reports, the symptoms most consistently associated with AAS use are extreme irritability, increased aggressiveness and mood swings. There are also a limited number of reports connecting AAS-associated aggressivity with violent acts including homicide, while reports of self-injurious behaviour associated ...

  3. Echocardiographic Findings in Power Athletes Abusing Anabolic Androgenic Steroids

    OpenAIRE

    Hajimoradi, Behzad; Kazerani, Hashem

    2012-01-01

    Purpose Anabolic androgenic steroids (AAS) abuse for improving physical appearance and performance in body builders is common and has been considered responsible for serious cardiovascular effects. Due to disagreement about cardiovascular side effects of these drugs in published articles, this case control study was designed to evaluate the echocardiographic findings in body builder athletes who are current and chronic abusers of these drugs. Methods Body builder athletes with continuous prac...

  4. Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction.

    Science.gov (United States)

    Low, M S Y; Vilcassim, S; Fedele, P; Grigoriadis, G

    2016-04-01

    Excessive anabolic androgenic steroids (both exogenous and endogenous) are known causes of polycythaemia and ischaemic cardiovascular events. Despite this, they are commonly forgotten in the workup of patients. We report a case of exogenous anabolic androgenic steroid-induced polycythaemia and stroke and explore possible pitfalls for clinicians. PMID:27062206

  5. 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…

  6. 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)

  7. 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...

  8. 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.

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

    Science.gov (United States)

    Kaur, Satwant; Baynes, Alice; Lockyer, Anne E; Routledge, Edwin J; Jones, Catherine S; Noble, Leslie R; Jobling, Susan

    2016-01-01

    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.

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

    Science.gov (United States)

    Lockyer, Anne E.; Routledge, Edwin J.; Jones, Catherine S.; Noble, Leslie R.; Jobling, Susan

    2016-01-01

    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. PMID:27448327

  11. 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…

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Kathy Bailey

    Full Text Available 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.

  14. 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

  15. [Myoanabolic steroids and selective androgen receptor modulators: mechanism of action and perspectives].

    Science.gov (United States)

    Tóth, Miklós

    2009-11-01

    Interest in anabolic steroids has been renewed in the last decade with the discovery of tissue-selective androgen receptor modulators exhibiting high myotropic and small androgenic activity. An explanation put forward by us in 1982 for the mechanism of the preferential myotropic effect of nandrolone (19-nortestosterone) exploits the fundamental difference between the 5alpha-reductase concentrations in skeletal muscle and androgenic target tissue. In androgenic tissue, testosterone is converted to the more potent 5alpha-dihydrotestosterone whereas nandrolone is converted to a less potent derivative. As 5alpha-reduction is negligible in skeletal muscle, this explains why nandrolone shows a greater myotropic to androgenic ratio when compared with testosterone. Anabolic steroids that do not undergo 5alpha-reduction exert myotropic-androgenic dissociation because their effect in androgenic tissues is not amplified by 5alpha-reduction. Tissue selectivity by receptor modulators may be achieved by inducing specific conformational changes of the androgen receptor that affect its interaction with transcriptional coregulators. Anabolic activity is mediated by the stimulation of ribosomal RNA synthesis therefore regulation of this synthesis by anabolic steroids would deserve detailed studies.

  16. Application of the theory of planned behaviour to explain adult male anabolic androgenic steroid use among gym users

    OpenAIRE

    Ager, Harry

    2015-01-01

    Background and aims: In the UK, the illegal use of anabolic androgenic steroids (steroids) among recreational gym-users has been increasing alongside a growth in the number of steroid-users accessing harm reduction services. Steroid-misuse has therefore become a public health concern. This study explored first-hand experiences of steroid-users’ attitudes towards and motivations for using steroids. It also explored whether and how societal and individual pressures as well as barriers and facil...

  17. [Recent aspects of therapy with androgenic and anabolic steroids].

    Science.gov (United States)

    Schambach, H; Nitschke, U; Kröhne, H J

    1983-11-15

    From the pharmacology of the therapeutically available androgen preparations and the clinical experience results that a highly dosed androgen long-term therapy is effectively possible only by testosterone esters which are to be injected intramuscularly (e.g. testosterone oenanthate). It is indicated in all forms of endocrine hypogonadism, certain aplastic anaemias and if necessary in extreme male high growth. In partial androgen deficiency (pubertas tarda, Klinefelter's syndrome, climacterium virile and others) orally applicable androgens such as testosterone-undecanoate (Andriol) and mesterolone (Vistimon) can be used. The latter is to be preferred when a hyperoestrogenism is present, e.g. in liver cirrhosis. When 17-alpha-alkylated oral androgens are used, their often not sufficiently confirmed anabolic effect and their potential liver toxicity should more be taken into consideration. PMID:6666179

  18. Liver pathology associated with the use of anabolic-androgenic steroids

    DEFF Research Database (Denmark)

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

    1992-01-01

    This review examines the liver-damaging side effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly prov...

  19. 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...

  20. 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.

    2003-01-01

    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 o

  1. 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…

  2. 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:…

  3. 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…

  4. 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

  5. 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

  6. Anabolic-androgenic steroids decrease dendritic spine density in the nucleus accumbens of male rats.

    Science.gov (United States)

    Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I

    2016-08-25

    Recent studies have demonstrated that anabolic-androgenic steroids (AAS) modify cognitive processes such as decision making and behavioral flexibility. However, the neural mechanisms underlying these AAS-induced cognitive changes remain poorly understood. The mesocorticolimbic dopamine (DA) system, particularly the nucleus accumbens (Acb), is important for reward, motivated behavior, and higher cognitive processes such as decision making. Therefore, AAS-induced plasticity in the DA system is a potential structural substrate for the observed cognitive alterations. High doses of testosterone (the most commonly-used AAS) increase dendritic spine density in limbic regions including the amygdala and hippocampus. However, effects on Acb are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically for 8weeks with high-dose testosterone (7.5mg/kg in water with 13% cyclodextrin) or vehicle sc. Brains were stained by Golgi-Cox to analyze neuronal morphology in medium spiny neurons of the shell region of Acb (AcbSh). Eightweeks of testosterone treatment significantly decreased spine density in AcbSh compared to brains of vehicle-treated rats (F1,14=5.455, p<0.05). Testosterone did not significantly affect total spine number, dendritic length, or arborization measured by Sholl analysis. These results show that AAS alter neuronal morphology in AcbSh by decreasing spine density throughout the dendritic tree, and provides a potential mechanism for AAS to modify cognition and decision-making behavior. PMID:27238893

  7. Anabolic-androgenic steroids decrease dendritic spine density in the nucleus accumbens of male rats.

    Science.gov (United States)

    Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I

    2016-08-25

    Recent studies have demonstrated that anabolic-androgenic steroids (AAS) modify cognitive processes such as decision making and behavioral flexibility. However, the neural mechanisms underlying these AAS-induced cognitive changes remain poorly understood. The mesocorticolimbic dopamine (DA) system, particularly the nucleus accumbens (Acb), is important for reward, motivated behavior, and higher cognitive processes such as decision making. Therefore, AAS-induced plasticity in the DA system is a potential structural substrate for the observed cognitive alterations. High doses of testosterone (the most commonly-used AAS) increase dendritic spine density in limbic regions including the amygdala and hippocampus. However, effects on Acb are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically for 8weeks with high-dose testosterone (7.5mg/kg in water with 13% cyclodextrin) or vehicle sc. Brains were stained by Golgi-Cox to analyze neuronal morphology in medium spiny neurons of the shell region of Acb (AcbSh). Eightweeks of testosterone treatment significantly decreased spine density in AcbSh compared to brains of vehicle-treated rats (F1,14=5.455, p<0.05). Testosterone did not significantly affect total spine number, dendritic length, or arborization measured by Sholl analysis. These results show that AAS alter neuronal morphology in AcbSh by decreasing spine density throughout the dendritic tree, and provides a potential mechanism for AAS to modify cognition and decision-making behavior.

  8. Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile.

    Science.gov (United States)

    Hikichi, Yukiko; Yamaoka, Masuo; Kusaka, Masami; Hara, Takahito

    2015-10-15

    Selective androgen receptor modulators (SARMs) specifically bind to the androgen receptor and exert agonistic or antagonistic effects on target organs. In this study, we investigated the SARM activity of TSAA-291, previously known as a steroidal antiandrogen, in mice because TSAA-291 was found to possess partial androgen receptor agonist activity in reporter assays. In addition, to clarify the mechanism underlying its tissue selectivity, we performed comprehensive cofactor recruitment analysis of androgen receptor using TSAA-291 and dihydrotestosterone (DHT), an endogenous androgen. The androgen receptor agonistic activity of TSAA-291 was more obvious in reporter assays using skeletal muscle cells than in those using prostate cells. In castrated mice, TSAA-291 increased the weight of the levator ani muscle without increasing the weight of the prostate and seminal vesicle. Comprehensive cofactor recruitment analysis via mammalian two-hybrid methods revealed that among a total of 112 cofactors, 12 cofactors including the protein inhibitor of activated STAT 1 (PIAS1) were differently recruited to androgen receptor in the presence of TSAA-291 and DHT. Prostate displayed higher PIAS1 expression than skeletal muscle. Forced expression of the PIAS1 augmented the transcriptional activity of the androgen receptor, and silencing of PIAS1 by siRNAs suppressed the secretion of prostate-specific antigen, an androgen responsive marker. Our results demonstrate that TSAA-291 has SARM activity and suggest that TSAA-291 may induce different conformational changes of the androgen receptor and recruitment profiles of cofactors such as PIAS1, compared with DHT, to exert tissue-specific activity.

  9. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells.

    Science.gov (United States)

    Basile, John R; Binmadi, Nada O; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    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. PMID:23675320

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Dihydrotestosterone Administration Does Not Increase Intraprostatic Androgen Concentrations or Alter Prostate Androgen Action in Healthy Men: A Randomized-Controlled Trial

    OpenAIRE

    Page, Stephanie T; Lin, Daniel W.; Mostaghel, Elahe A.; Marck, Brett T.; Wright, Jonathan L; Wu, Jennifer; Amory, John K.; Peter S Nelson; Matsumoto, Alvin M.

    2010-01-01

    Exogenous dihydrotestosterone (DHT), which substantially raises serum DHT and lowers serum T, does not significantly alter intraprostatic androgen levels or androgen-responsive gene expression in healthy men.

  12. 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.

  13. Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children.

    Science.gov (United States)

    Majewska, Maria Dorota; Hill, Martin; Urbanowicz, Ewa; Rok-Bujko, Paulina; Bieńkowski, Przemysław; Namysłowska, Irena; Mierzejewski, Paweł

    2014-06-01

    Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers are not well defined. A strong gender bias typifying autism (it is 4-5 times more prevalent in males) suggests involvement of steroid hormones in autism pathobiology. In order to evaluate the potential roles of such hormones in autism, we compared the salivary levels of 22 steroids in prepubertal autistic male and female children from two age groups (3-4 and 7-9 years old) with those in healthy controls. The steroids were analyzed using gas chromatography-mass spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that autistic children had significantly higher salivary concentrations of many steroid hormones (both C21 and C19) than control children. These anomalies were more prominent in older autistic children and in boys. The levels of androgens (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates) were especially increased, indicative of precocious adrenarche and predictive of early puberty. The concentrations of the steroid precursor, pregnenolone, and of several pregnanolones were also higher in autistic than in healthy children, but cortisol levels were not different. Some steroids, whose levels are raised in autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and opioid neurotransmission, affecting brain development and functioning. These steroids may contribute to autism pathobiology and symptoms such as elevated anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We suggest that salivary levels of selected steroids may serve as biomarkers of autism pathology useful for monitoring the progress of therapy.

  14. ANDROGEN REGULATION OF PROSTATIC STEROID BINDING PROTEIN GENE TRANSCRIPTION

    Institute of Scientific and Technical Information of China (English)

    ZHANGYong-Lian; ZHOUZong-Xun; ZHANGYou-Duan; PARKERMalcolmG

    1989-01-01

    Prostatic steroid binding protein (PSBP) is a major protein secreted in the rat ventral prostate (V.P.) and also one of the components in seminal fluid, The potential importance of this protein in male fertility emerged from its ability of binding cholesterol which might modulate the proportion of phospholipids and cholesterol in sperm making it suitable

  15. 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

  16. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.

    Science.gov (United States)

    Dubois, Vanessa; Laurent, Michaël R; Jardi, Ferran; Antonio, Leen; Lemaire, Katleen; Goyvaerts, Lotte; Deldicque, Louise; Carmeliet, Geert; Decallonne, Brigitte; Vanderschueren, Dirk; Claessens, Frank

    2016-02-01

    Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and β-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men.

  17. Steroid induced central serous retinopathy following follicular unit extraction in androgenic alopecia

    Directory of Open Access Journals (Sweden)

    Rakesh Tilak Raj

    2016-06-01

    Full Text Available Dermatologists for various conditions and procedures commonly use corticosteroids worldwide. The development of central serous retinopathy is a lesser known complication occurring in <10% of the cases with steroid use. This case report highlights the development of central serous retinopathy after prescribing low dose of prednisolone 20 mg per day for androgenic alopecia during post-surgical follicular unit extraction (FUE surgery follow-up that recovered spontaneously after gradual withdrawal of steroids. Therefore, awareness is required for its early detection and management as it has a potential of causing irreversible visual impairment. [Int J Basic Clin Pharmacol 2016; 5(3.000: 1152-1155

  18. 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.

  19. 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. PMID:27535042

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

    OpenAIRE

    Cooper, C. J.; Noakes, T.D.; Dunne, T; M.I. Lambert; 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 n...

  1. Iatrogenic dependence of anabolic-androgenic steroid in an Indian non-athletic woman

    OpenAIRE

    Tripathi, Adarsh; Tekkalaki, Bheemsain; Saxena, Shashwat; Dandu, Himanshu

    2014-01-01

    Anabolic-androgenic steroids (AAS) are increasingly being used by athletes and youngsters to become masculine and to loose body fat. Long-term consumption of AAS causes multiple physical and psychological morbidities. Research has also concluded that AAS have addictive potential and AAS abuse is commonly found with other substance abuse. Abuse of AAS is rare in eastern countries. Abuse among women is even rarer. Here is a case report of an Indian woman, who was prescribed nandrolone decanoate...

  2. Anabolic androgenic steroids and central monoaminergic systems : Supratherapeutic doses of nandrolone decanoate affect dopamine and serotonin

    OpenAIRE

    Birgner, Carolina

    2008-01-01

    Supratherapeutic doses of anabolic androgenic steroids (AASs) are administered, not only as performance-enhancing drugs in the world of sports, but also in order to modify behaviour. AAS abusers are at risk of developing serious physical and psychological side effects such as dependence and aggressive behaviour. The aim of this thesis was to investigate the impact of supratherapeutic doses of nandrolone decanoate after subchronic administration on dopamine and serotonin pathways involved in d...

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

    OpenAIRE

    Đorđević Vitomir; Stanković Ivan; Stipac Vlahović Alja; Putniković Biljana; Nešković Aleksandar N.

    2012-01-01

    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 2...

  4. Epidemiological and neurobiological evidence for misuse of anabolic-androgenic steroids

    OpenAIRE

    Kindlundh, Anna MS

    2002-01-01

    Misuse of anabolic-androgenic steroids (AAS), is attributed to elite athletes and body builders. The attentive involvement of AAS in acts of violence seen in society has raised interest to evaluate the importance of social, psychological and neurobiological mechanisms that underlie the psychiatric states associated with onset of controlled misuse, its maintenance, and via abuse its transition to addiction. The objective of this thesis is to examine whether misuse of AAS shares mechanisms with...

  5. Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem.

    Science.gov (United States)

    Rahnema, C D; Crosnoe, L E; Kim, E D

    2015-03-01

    Colloquially referred to by various misleading monikers ('pro-hormones', 'natural steroids', 'testosterone boosters', etc.) designer anabolic steroids have been popular now for over a decade as a way to achieve classic anabolic steroid-like results from products sold in the legal marketplace. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age. Despite recent regulatory efforts that have banned specific compounds, many anabolic-androgenic steroids (AAS) remain available in over-the-counter dietary supplements that are legally sold in the United States. Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products. While some of these side effects may be reversible, more aggressive use may result in more permanent end-organ damage as has been previously described for the case of aggressive AAS users (Rahnema et al., Fertil Steril, 2014). Designer AAS remain easily available for purchase in over-the-counter bodybuilding supplements and these products appear to be increasingly popular, despite the known health risks associated with their use. We conducted a systematic search to identify the designer steroids that are most commonly sold in dietary supplements as of April 2014 and review what is known regarding their potency and toxicity. We propose that the impact of AAS use on the reproductive and hormonal health of men is underestimated in the literature owing to previous studies' failure to account for designer steroid use. Lastly, we make clinical recommendations to help physicians steer patients away from potentially harmful supplements, and summarize key regulatory obstacles that have allowed potent androgens to remain unregulated in the legal marketplace. PMID:25684733

  6. Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem.

    Science.gov (United States)

    Rahnema, C D; Crosnoe, L E; Kim, E D

    2015-03-01

    Colloquially referred to by various misleading monikers ('pro-hormones', 'natural steroids', 'testosterone boosters', etc.) designer anabolic steroids have been popular now for over a decade as a way to achieve classic anabolic steroid-like results from products sold in the legal marketplace. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age. Despite recent regulatory efforts that have banned specific compounds, many anabolic-androgenic steroids (AAS) remain available in over-the-counter dietary supplements that are legally sold in the United States. Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products. While some of these side effects may be reversible, more aggressive use may result in more permanent end-organ damage as has been previously described for the case of aggressive AAS users (Rahnema et al., Fertil Steril, 2014). Designer AAS remain easily available for purchase in over-the-counter bodybuilding supplements and these products appear to be increasingly popular, despite the known health risks associated with their use. We conducted a systematic search to identify the designer steroids that are most commonly sold in dietary supplements as of April 2014 and review what is known regarding their potency and toxicity. We propose that the impact of AAS use on the reproductive and hormonal health of men is underestimated in the literature owing to previous studies' failure to account for designer steroid use. Lastly, we make clinical recommendations to help physicians steer patients away from potentially harmful supplements, and summarize key regulatory obstacles that have allowed potent androgens to remain unregulated in the legal marketplace.

  7. Modern techniques for the determination of anabolic-androgenic steroid doping in the horse.

    Science.gov (United States)

    McKinney, Andrew R

    2009-07-01

    Control of the use of performance-affecting substances in the horse is critical to the integrity of a wide range of equine sports, with major implications for both animal welfare and revenue streams. One class of medications enjoying particular public notoriety is the anabolic-androgenic steroid group, as highlighted by the recent 'Big Brown' affair and Congressional inquiries into the use of steroids in professional sports, including horse racing, in the USA. This review examines the latest developments pertaining to the analytical detection of these substances in equine biological samples and the supporting regulatory environment. Consideration is given to the full variety of sample matrices available, together with modern sample preparative approaches and instrumental techniques. Issues concerning the regulation of endogenous steroids, including thresholds where applicable, are also discussed.

  8. Use of anabolic-androgenic steroids masking the diagnosis of pleural tuberculosis: a case report

    Directory of Open Access Journals (Sweden)

    de Larrea Carlos

    2009-01-01

    Full Text Available Abstract Introduction Tuberculous pleural effusions are not always easy to diagnose but the presence of a lymphocyte-rich exudate associated with an increased adenosine deaminase level and a positive skin test result are highly sensitive diagnostic signs. Case presentation We report a case of pleural tuberculosis in a 31-year-old white male patient from Caracas, Venezuela who was negative for human immunodeficiency virus and presented 2 weeks after injecting the anabolic-androgenic steroid nandrolone decanoate, in whom all the tests for tuberculosis were initially negative; an eosinophilic pleural effusion with a low adenosine deaminase level, a negative tuberculin skin test and negative for acid-fast bacilli staining and culture of the pleural fluid. After excluding other causes of eosinophilic pleural effusion malignant pleural effusion was suspected. The patient did not return until 4 months later. The second thoracentesis obtained a pleural fluid suggestive for tuberculosis, with a predominance of lymphocytes, an elevated adenosine deaminase level (51 U/l and a positive tuberculin skin test. Culture of pleural fragments confirmed pleural tuberculosis. Conclusion This case suggests that the use of an anabolic-androgenic steroid masks the definitive diagnosis of pleural tuberculosis by changing the key diagnostic parameters of the pleural fluid, a finding not previously reported. Available evidence of the effects of anabolic steroids on the immune system also suggests that patients using anabolic-androgenic steroids might be susceptible to developing tuberculosis in either reactivating a latent infection or facilitating development of the disease after a recent infection.

  9. Photoperiodic regulation of androgen receptor and steroid receptor coactivator-1 in Siberian hamster brain.

    Science.gov (United States)

    Tetel, Marc J; Ungar, Todd C; Hassan, Brett; Bittman, Eric L

    2004-11-24

    Seasonal changes in the neuroendocrine actions of gonadal steroid hormones are triggered by fluctuations in daylength. The mechanisms responsible for photoperiodic influences upon the feedback and behavioral effects of testosterone in Siberian hamsters are poorly understood. We hypothesized that daylength regulates the expression of androgen receptor (AR) and/or steroid receptor coactivator-1 (SRC-1) in specific forebrain regions. Hamsters were castrated and implanted with either oil-filled capsules or low doses of testosterone; half of the animals remained in 16L/8D and the rest were kept in 10L/14D for the ensuing 70 days. The number of AR-immunoreactive (AR-ir) cells was regulated by testosterone in medial amygdala and caudal arcuate, and by photoperiod in the medial preoptic nucleus and the posterodorsal medial amygdala. A significant interaction between photoperiod and androgen treatment was found in medial preoptic nucleus and posterodorsal medial amygdala. The molecular weight and distribution of SRC-1 were similar to reports in other rodent species, and short days reduced the number of SRC-1-ir cells in posteromedial bed nucleus of the stria terminalis (BNST) and posterodorsal medial amygdala. A significant interaction between androgen treatment and daylength in regulation of SRC-1-ir was found in anterior medial amygdala. The present results indicate that daylength-induced fluctuations in SRC-1 and AR expression may contribute to seasonally changing effects of testosterone.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. CHAMP Symposium on Androgens, Anabolic Steroids, and Related Substances: What We Know and What We Need to Know.

    Science.gov (United States)

    Givens, Melissa L; Deuster, Patricia A; Kupchak, Brian R

    2016-07-01

    The Consortium of Health and Military Performance hosted a symposium in April 2015 entitled "Androgens, Anabolic Steroids, and Related Substances: What We Know and What We Need to Know" in response to concerns from the field regarding Anabolic Androgenic Steroids use by U.S. service members. The symposium was attended by military and civilian subject-matter experts in sports medicine and anabolic steroids and was held at the United Service Organizations (Naval Support Activity Bethesda) in Bethesda, Maryland. The expert panel was charged to define the way ahead in terms of androgen use, education, research, relevant policies and guidelines, and other concerns with particular relevancy to Special Operations Forces. The conference concluded with the following recommendations on these several key issues (1) connecting with users, (2) education and intervention, (3) knowledge and research gaps, and (4) establishing an information clearinghouse and clinical repository. PMID:27391622

  15. CHAMP Symposium on Androgens, Anabolic Steroids, and Related Substances: What We Know and What We Need to Know.

    Science.gov (United States)

    Givens, Melissa L; Deuster, Patricia A; Kupchak, Brian R

    2016-07-01

    The Consortium of Health and Military Performance hosted a symposium in April 2015 entitled "Androgens, Anabolic Steroids, and Related Substances: What We Know and What We Need to Know" in response to concerns from the field regarding Anabolic Androgenic Steroids use by U.S. service members. The symposium was attended by military and civilian subject-matter experts in sports medicine and anabolic steroids and was held at the United Service Organizations (Naval Support Activity Bethesda) in Bethesda, Maryland. The expert panel was charged to define the way ahead in terms of androgen use, education, research, relevant policies and guidelines, and other concerns with particular relevancy to Special Operations Forces. The conference concluded with the following recommendations on these several key issues (1) connecting with users, (2) education and intervention, (3) knowledge and research gaps, and (4) establishing an information clearinghouse and clinical repository.

  16. Determination of anabolic-androgenic steroid adulterants in counterfeit drugs by UHPLC-MS/MS.

    Science.gov (United States)

    Cho, So-Hyun; Park, Hyoung Joon; Lee, Ji Hyun; Do, Jung-Ah; Heo, Seok; Jo, Jeong Hwa; Cho, Sooyeul

    2015-01-01

    Anabolic-androgenic steroids (AASs) have been illegally used in counterfeit drugs to improve the performance of athletes. In addition, AASs have been used for cosmetic purpose by non-athletes. To determine the presence of 26 AASs, an analysis method using ultra-liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. The validated method was applied to 19 counterfeit drugs collected from the Internet and off-line markets during 2014. Nearly 50% (9/19) of the samples contained one of these 26 AASs. In addition, the concentration ranges of the AASs ranged from 0.09 to 119,228.57 mg/kg in the suspected samples. The determined AASs primarily consisted of testosterone and testosterone 17-propionate (26%) followed by boldenone (21%). These results indicate the adulteration of over-the-counter counterfeit drugs, and the continuous monitoring of counterfeit drugs or dubious dietary supplements containing anabolic steroids is warranted.

  17. The role of androgenic steroids in shaping social phenotypes across the lifespan in male marmosets (Callithrix spp.).

    Science.gov (United States)

    French, Jeffrey A

    2013-03-01

    Steroid hormones, particularly androgens and their metabolic derivatives, play a prominent role in shaping morphological, behavioral, and social phenotypes in many organisms, including primates. This paper reviews the endocrine correlates of development in male marmoset monkeys of the genus Callithrix (C. kuhlii and C. geoffroyi). A lifespan developmental perspective is adopted, in which our knowledge of hormone effects and profiles from prenatal periods through old age is described. Prenatal steroid hormones appear to play a prominent role in shaping behavioral and morphological phenotypes both the prepartum and in the early postpartum periods of life, with exposure to high gestational androgen associated with reduced fetal growth and lower levels of juvenile play. Early postnatal elevations in androgen levels in males are ubiquitous in Callithrix, and play a role in the further differentiation of male genital morphology and behavior. Changes in androgens as males approach puberty are similar to the conventional primate pattern, and unlike in female marmosets, gonadal steroidogenesis appears to be independent of social context. In adults, androgens appear to be an important modulator of paternal responsiveness to infants, since androgens are low at times when males typically engage in maximal levels of care, and fathers that care for offspring extensively appear to have lower androgen levels than fathers that are less involved in offspring care. Finally, aging in male marmosets is associated with reduced androgen levels. This reduction appears to be attributable to deficits in central mechanisms, since experimental induction and inhibition of gonadal steroid synthesis and release appears to be normal in older males. Together, these results suggest a complex picture of lifetime involvement of androgens in shaping marmoset phenotypes. PMID:23335110

  18. 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. PMID:27443207

  19. 17β-trenbolone, an anabolic–androgenic steroid as well as an environmental hormone, contributes to neurodegeneration

    International Nuclear Information System (INIS)

    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

  20. 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

  1. Mycobacterium smegmatis synthesizes in vitro androgens and estrogens from different steroid precursors.

    Science.gov (United States)

    Dlugovitzky, Diana G; Fontela, María Sol; Martinel Lamas, Diego J; Valdez, Ricardo A; Romano, Marta C

    2015-07-01

    Fast-growing mycobacteria such as Mycobacterium sp. and Mycobacterium smegmatis degrade natural sterols. They are a model to study tuberculosis. Interestingly, M. smegmatis has been found in river effluents derived from paper production, and therefore, it would be important to gain further insight into its capacity to synthesize steroids that are potential endocrine disruptors affecting the development and reproduction of fishes. To our knowledge, the capacity of M. smegmatis to synthesize estrogens and even testosterone has not been previously reported. Therefore, the objective of this study was to investigate the capacity of M. smegmatis to synthesize in vitro testosterone and estrogens from tritiated precursors and to investigate the metabolic pathways involved. Results obtained by thin-layer chromatography showed that (3)H-progesterone was transformed to 17OH-progesterone, androstenedione, testosterone, estrone, and estradiol after 6, 12, or 24 h of incubation. (3)H-androstenedione was transformed into testosterone and estrogens, mainly estrone, and (3)H-testosterone was transformed to estrone and androstenedione. Incubation with (3)H-dehydroepiandrosterone rendered androstenediol, testosterone, and estrogens. This ability to transform less potent sex steroids like androstenedione and estrone into other more active steroids like testosterone and estradiol or vice versa suggests that M. smegmatis can influence the amount of self-synthesized strong androgens and estrogens and can transform those found in the environment. PMID:25994226

  2. BINDING OF STEROIDS AND ENVIRONMENTAL CHEMICALS TO THE RAINBOW TROUT ANDROGEN RECEPTOR ALPHA EXPRESSED IN COS CELLS

    Science.gov (United States)

    Binding of Steroids and Environmental Chemicals to the Rainbow Trout Androgen Receptor Alpha Expressed in COS Cells. Mary C. Cardon, L. Earl Gray. Jr., Phillip C. Hartig and Vickie S. Wilson U.S. Environmental Protection Agency, ORD, NHEERL, Reproductive Toxicology...

  3. 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…

  4. 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.

  5. Treadmill exercise training prevents myocardial mechanical dysfunction induced by androgenic-anabolic steroid treatment in rats.

    Directory of Open Access Journals (Sweden)

    Danilo S Bocalini

    Full Text Available Elevated concentrations of testosterone and its synthetic analogs may induce changes in cardiovascular function. However, the effects of the combination of anabolic/androgenic steroid (AAS treatment and exercise training on systolic and diastolic cardiac function are poorly understood. In the present study, we aimed to investigate the effects of low-dose steroid treatment (stanozolol on cardiac contractile parameters when this steroid treatment was combined with exercise training in rats and the effects of chronic steroid treatment on the Frank-Starling (length-tension curves relationship. Male Wistar rats were randomly assigned to one of four groups: U (untrained, US (untrained and treated with stanozolol 5 mg/kg/week, T (trained, 16 m/min/1 h and TS (trained and treated with stanozolol 5 mg/kg/week. Continuous exercise training was conducted 5 days/week for 8 consecutive weeks. The speed of the treadmill was gradually increased to a final setting of 16 m/min/1 h. Experiments were divided into two independent series: 1 central hemodynamic analysis for mean arterial blood pressure (MAP and cardiac output (CO measurements and 2 isolated papillary muscle preparation in Krebs solution. Stanozolol treatment significantly increased the MAP and the heart size in untrained and trained rats (U 113±2; T 106±2; US 138±8 and TS 130±7 mmHg. Furthermore, stanozolol significantly decreased developed tension and dT/dt (maximal and minimal in U rats. However, the developed tension was completely restored by training. The Frank/Starling relationship was impaired in rats treated with stanozolol; however, again, training completely restored diastolic function. Taken together, the present data suggest that AAS treatment is able to decrease cardiac performance (systolic and diastolic functions. The combination of stanozolol and physical training improved cardiac performance, including diastolic and systolic functions, independent of changes in central

  6. Treadmill exercise training prevents myocardial mechanical dysfunction induced by androgenic-anabolic steroid treatment in rats.

    Science.gov (United States)

    Bocalini, Danilo S; Beutel, Abram; Bergamaschi, Cássia T; Tucci, Paulo J; Campos, Ruy R

    2014-01-01

    Elevated concentrations of testosterone and its synthetic analogs may induce changes in cardiovascular function. However, the effects of the combination of anabolic/androgenic steroid (AAS) treatment and exercise training on systolic and diastolic cardiac function are poorly understood. In the present study, we aimed to investigate the effects of low-dose steroid treatment (stanozolol) on cardiac contractile parameters when this steroid treatment was combined with exercise training in rats and the effects of chronic steroid treatment on the Frank-Starling (length-tension curves) relationship. Male Wistar rats were randomly assigned to one of four groups: U (untrained), US (untrained and treated with stanozolol 5 mg/kg/week), T (trained, 16 m/min/1 h) and TS (trained and treated with stanozolol 5 mg/kg/week). Continuous exercise training was conducted 5 days/week for 8 consecutive weeks. The speed of the treadmill was gradually increased to a final setting of 16 m/min/1 h. Experiments were divided into two independent series: 1) central hemodynamic analysis for mean arterial blood pressure (MAP) and cardiac output (CO) measurements and 2) isolated papillary muscle preparation in Krebs solution. Stanozolol treatment significantly increased the MAP and the heart size in untrained and trained rats (U 113±2; T 106±2; US 138±8 and TS 130±7 mmHg). Furthermore, stanozolol significantly decreased developed tension and dT/dt (maximal and minimal) in U rats. However, the developed tension was completely restored by training. The Frank/Starling relationship was impaired in rats treated with stanozolol; however, again, training completely restored diastolic function. Taken together, the present data suggest that AAS treatment is able to decrease cardiac performance (systolic and diastolic functions). The combination of stanozolol and physical training improved cardiac performance, including diastolic and systolic functions, independent of changes in central hemodynamic

  7. 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.

  8. 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.

  9. The anabolic androgenic steroid nandrolone decanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats.

    Directory of Open Access Journals (Sweden)

    Stephan P Frankenfeld

    Full Text Available The abuse of anabolic androgenic steroids (AAS may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g(-1 body weight once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX, and the activity of catalase, glutathione peroxidase (GPx and total superoxide dismutase (SOD, as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.

  10. Novel Nor-Homo- and Spiro-Oxetan- Steroids Target the Human Androgen Receptor and Act as Antiandrogens.

    Science.gov (United States)

    Thiele, Marie; Rabe, Sebastian; Hessenkemper, Wiebke; Roell, Daniela; Bartsch, Sophie; Kraft, Florian; Abraham, Tsion E; Houtsmuller, Adriaan B; van Royen, Martin E; Giannis, Athanassios; Baniahmad, Aria

    2014-06-01

    The prostate adenocarcinoma is the cancer with the highest incidence for men in Western countries. Targeting the androgen receptor (AR) by antagonists is used as hormone therapy for prostate cancer (PCa), however, eventually therapy resistance occurs in most patients. In most of these cancer the AR signaling is active and thus AR remains an important drug target. Since many years we are characterizing novel chemical structural platforms to provide a broader possibility for compounds that bind to and act as AR antagonists. Here, we describe the chemical synthesis of a battery of novel steroidal derivatives as nor-homo-, spiro-oxolan- and spiro-oxetan- steroids. They modulate the transcriptional activity of the human AR. As AR antagonists, the spiro-oxetan- steroid derivatives seem to be the most potent steroid derivatives. They inhibit the transcriptional activity of both wild-type AR as well as the AR mutant T877A. In line with this, these compounds bind to the human AR and inhibit the proliferation of the human androgen-dependent growing PCa cell line LNCaP. Interestingly, the castration-resistant AR expressing human PC3-AR cells are also growth inhibited. On mechanistic level, fluorescence resonance energy transfer (FRET) assays with living cells indicate that the androgen-induced N/C terminal interaction of the AR is inhibited by the investigated compounds. Using fluorescence recovery after photobleaching (FRAP) assays in living cells suggest a higher mobility of the AR in the cell nuclei in the presence of spiro-oxetan- steroidal antagonists. Together, these findings suggest that spiro-oxetan- steroids are very useful as a chemical platform for novel AR antagonists.

  11. Alteration of reproductive steroids of male winter flounder (Pleuronectes americanus) chronically exposed to low levels of crude oil in sediments

    International Nuclear Information System (INIS)

    When male winter flounder (Pleuronectes americanus) were held in seawater for 4 months exposed to sand treated with five low levels of crude oil, there was a significant reduction in testosterone and 11-ketotestosterone glucuronides in blood plasma. At the two higher levels of oil the concentration of plasma glucuronides were similar but very significantly lower than the controls or the three lower concentrations of oil. For both androgens the ratio of glucuronides to free steroids declined in a stepwise fashion. Free testosterone and 11-ketotestosterone plasma levels were not significantly affected by any concentration of oil in the sediment. Liver weights as a percentage of body weight were significantly increased at the two highest levels of oil in sediments, but neither body weights nor testes weights were altered by exposure to oil. It has been suggested that androgen glucuronides can function as pheromones in some fish and this is one potentially deleterious effect of exposure to oil. 33 refs., 1 tab

  12. 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. PMID:20188494

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

    OpenAIRE

    Alsaeed, Ibrahim; Alabkal, Jarrah R.

    2015-01-01

    Background 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. Methods A cross sectional s...

  14. The aetiology and trajectory of anabolic-androgenic steroid use initiation: a systematic review and synthesis of qualitative research

    OpenAIRE

    Sagoe, Dominic; Andreassen, Cecilie Schou; Pallesen, Ståle

    2014-01-01

    Background: To our knowledge, there has never been a systematic review and synthesis of the qualitative literature on the trajectory and aetiology of nonmedical anabolic-androgenic steroid (AAS) use. Methods: We systematically reviewed and synthesized qualitative literature gathered from searches in PsycINFO, PubMed, ISI Web of Science, Google Scholar, and reference lists of relevant literature to investigate AAS users’ ages of first use and source(s), history prior to use, and motiv...

  15. The aetiology and trajectory of anabolic-androgenic steroid use initiation: a systematic review and synthesis of qualitative research

    OpenAIRE

    Sagoe, Dominic; Andreassen, Cecilie Schou; Pallesen, Ståle

    2014-01-01

    Background. To our knowledge, there has never been a systematic review and synthesis of the qualitative literature on the trajectory and aetiology of nonmedical anabolic-androgenic steroid (AAS) use. Methods. We systematically reviewed and synthesized qualitative literature gathered from searches in PsycINFO, PubMed, ISI Web of Science, Google Scholar, and reference lists of relevant literature to investigate AAS users’ ages of first use and source(s), history prior to use, and motives/dr...

  16. Analysis of Androgenic Steroids in Environmental Waters by Large-volume Injection Liquid Chromatography Tandem Mass Spectrometry

    OpenAIRE

    Backe, Will J.; Ort, Christoph; Brewer, Alex J.; Field, Jennifer A.

    2011-01-01

    A new method was developed for the analysis of natural and synthetic androgenic steroids and their selected metabolites in aquatic environmental matrices using direct large-volume injection (LVI) high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). Method accuracy ranged from 88 to 108% for analytes with well-matched internal standards. Precision, quantified by relative standard deviation (RSD), was less than 12%. Detection limits for the method ranged from 1.2 to 3...

  17. Eating disorders and anabolic androgenic steroids in males - similarities and differences in self-image and psychiatric symptoms

    OpenAIRE

    Björk, Tabita; Skårberg, Kurt; Engström, Ingemar

    2013-01-01

    Background Body dissatisfaction is common among both females and males. Dissatisfaction with the body is a risk factor both for onset of eating disorders and for abuse of anabolic androgenic steroids (AAS). Few studies have however investigated if there are other similarities in respect to self-image or psychiatric symptoms between clinical samples of eating disordered males and males in treatment for negative effects of AAS use. Aim The aim of this study was to compare two clinical samples, ...

  18. The Role of Androgenic Steroids in Shaping Social Phenotypes Across the Lifespan in Male Marmosets (Callithrix spp.)

    OpenAIRE

    FRENCH, JEFFREY A.

    2012-01-01

    Steroid hormones, particularly androgens and their metabolic derivatives, play a prominent role in shaping morphological, behavioral, and social phenotypes in many organisms, including primates. This paper reviews the endocrine correlates of development in male marmoset monkeys of the genus Callithrix (C. kuhlii and C. geoffroyi). A lifespan developmental perspective is adopted, in which our knowledge of hormone effects and profiles from prenatal periods through old age are described. Prenata...

  19. 5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis.

    Science.gov (United States)

    Traish, Abdulmaged M; Guay, Andre T; Zitzmann, Michael

    2014-12-01

    5α-reductases, a unique family of enzymes with a wide host of substrates and tissue distributions, play a key role in the metabolism of androgens, progestins, mineralocorticoids and glucocorticoids. These enzymes are the rate-limiting step in the synthesis of a host of neurosteroids, which are critical for central nervous system function. Androgens and glucocorticoids modulate mitochondrial function, carbohydrate, protein and lipid metabolism and energy balance. Thus, the inhibition of these regulatory enzymes results in an imbalance in steroid metabolism and clearance rates, which leads to altered physiological processes. In this report, we advance the hypothesis that inhibition of 5α-reductases by finasteride and dutasteride alters not only steroid metabolism but also interferes with the downstream actions and signaling of these hormones. We suggest that finasteride and dutasteride inhibit 5α-reductase activities and reduce the clearance of glucocorticoids and mineralocorticoids, potentiating insulin resistance, diabetes and vascular disease. PMID:25460297

  20. MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions.

    Science.gov (United States)

    Nieschlag, Eberhard; Vorona, Elena

    2015-08-01

    Anabolic androgenic steroids (AASs) are appearance and performance-enhancing drugs (APEDs) used in competitive athletics, in recreational sports, and by body-builders. The global lifetime prevalence of AASs abuse is 6.4% for males and 1.6% for women. Many AASs, often obtained from the internet and dubious sources, have not undergone proper testing and are consumed at extremely high doses and in irrational combinations, also along with other drugs. Controlled clinical trials investigating undesired side effects are lacking because ethical restrictions prevent exposing volunteers to potentially toxic regimens, obscuring a causal relationship between AASs abuse and possible sequelae. Because of the negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis, in men AASs cause reversible suppression of spermatogenesis, testicular atrophy, infertility, and erectile dysfunction (anabolic steroid-induced hypogonadism). Should spermatogenesis not recover after AASs abuse, a pre-existing fertility disorder may have resurfaced. AASs frequently cause gynecomastia and acne. In women, AASs may disrupt ovarian function. Chronic strenuous physical activity leads to menstrual irregularities and, in severe cases, to the female athlete triad (low energy intake, menstrual disorders and low bone mass), making it difficult to disentangle the effects of sports and AASs. Acne, hirsutism and (irreversible) deepening of the voice are further consequences of AASs misuse. There is no evidence that AASs cause breast carcinoma. Detecting AASs misuse through the control network of the World Anti-Doping Agency (WADA) not only aims to guarantee fair conditions for athletes, but also to protect them from medical sequelae of AASs abuse. PMID:25805894

  1. MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions.

    Science.gov (United States)

    Nieschlag, Eberhard; Vorona, Elena

    2015-08-01

    Anabolic androgenic steroids (AASs) are appearance and performance-enhancing drugs (APEDs) used in competitive athletics, in recreational sports, and by body-builders. The global lifetime prevalence of AASs abuse is 6.4% for males and 1.6% for women. Many AASs, often obtained from the internet and dubious sources, have not undergone proper testing and are consumed at extremely high doses and in irrational combinations, also along with other drugs. Controlled clinical trials investigating undesired side effects are lacking because ethical restrictions prevent exposing volunteers to potentially toxic regimens, obscuring a causal relationship between AASs abuse and possible sequelae. Because of the negative feedback in the regulation of the hypothalamic-pituitary-gonadal axis, in men AASs cause reversible suppression of spermatogenesis, testicular atrophy, infertility, and erectile dysfunction (anabolic steroid-induced hypogonadism). Should spermatogenesis not recover after AASs abuse, a pre-existing fertility disorder may have resurfaced. AASs frequently cause gynecomastia and acne. In women, AASs may disrupt ovarian function. Chronic strenuous physical activity leads to menstrual irregularities and, in severe cases, to the female athlete triad (low energy intake, menstrual disorders and low bone mass), making it difficult to disentangle the effects of sports and AASs. Acne, hirsutism and (irreversible) deepening of the voice are further consequences of AASs misuse. There is no evidence that AASs cause breast carcinoma. Detecting AASs misuse through the control network of the World Anti-Doping Agency (WADA) not only aims to guarantee fair conditions for athletes, but also to protect them from medical sequelae of AASs abuse.

  2. 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. PMID:26784694

  3. 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.

  4. Troubled social background of male anabolic-androgenic steroid abusers in treatment

    Directory of Open Access Journals (Sweden)

    Skarberg Kurt

    2007-07-01

    Full Text Available Abstract Background The aim of this study was to investigate the social background and current social situation of male abusers of anabolic-androgenic steroids (AAS. Methods We compared thirty-four AAS-abusing patients from an Addiction Centre (AC with two groups, 18 users and 259 non-users of AAS from a public gym in Orebro, Sweden. The study is based on semi-structured interviews and questionnaires. Results Histories of a troubled childhood as well as current social disadvantage were both more frequent among the AAS users. Users also reported poor relationships with their parents and almost half of them had experienced physical or mental abuse. The AC group's experiences from school were mostly negative, and included concentration problems, boredom and learning difficulties. Their current circumstance included abuse of other drugs, battering of spouses and other criminality such as assault, illegal possession of weapons and theft. Conclusion In conclusion, this study shows that abusers of AAS often have a troubled social background. This underlines the importance of making a thorough social assessment as a part of the treatment programme. The results of the study may help in directing appropriate questions relevant to the abuse of AAS.

  5. Aggression Is Associated With Increased Anabolic-Androgenic Steroid Use Contemplation Among Adolescents.

    Science.gov (United States)

    Sagoe, Dominic; Mentzoni, Rune A; Hanss, Daniel; Pallesen, Ståle

    2016-09-18

    We investigated the relationship between aggression and anabolic-androgenic steroid (AAS) use intent among adolescents. A nationally representative sample of Norwegian 18-year-olds (N = 1,334, females = 58.7%) took part in a survey in 2013 (response rate = 64.9%). Participants completed the physical and verbal subscales of the Short-Form Buss-Perry Aggression Questionnaire, the Intent to use AAS Scale, the Alcohol Use Disorders Identification Test-Consumption, and the Hospital Anxiety and Depression Scale. They also provided demographic information and answered questions about AAS use, gambling participation, as well as cigarette and snus use. Descriptive statistics and multinomial logistic regression were used to analyze the data. Lifetime and past year prevalence of AAS use was 0.1%. Between 0.4% and 1.7% of participants disclosed intent to use while between 1.1% and 2.5% expressed neutral intent to initiate AAS use. Compared to persons low on aggression, individuals high on aggression were more likely to report intent and curiosity towards initiating AAS use. Our findings indicate that aggression is a risk factor for AAS use contemplation among adolescents. PMID:27356242

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

    Science.gov (United States)

    McBride, J Abram; Coward, Robert M

    2016-01-01

    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. PMID:26908067

  7. Identification of Novel Steroidal Androgen Receptor Degrading Agents Inspired by Galeterone 3β-Imidazole Carbamate.

    Science.gov (United States)

    Purushottamachar, Puranik; Kwegyir-Afful, Andrew K; Martin, Marlena S; Ramamurthy, Vidya P; Ramalingam, Senthilmurugan; Njar, Vincent C O

    2016-07-14

    Degradation of all forms of androgen receptors (ARs) is emerging as an advantageous therapeutic paradigm for the effective treatment of prostate cancer. In continuation of our program to identify and develop improved efficacious novel small-molecule agents designed to disrupt AR signaling through enhanced AR degradation, we have designed, synthesized, and evaluated novel C-3 modified analogues of our phase 3 clinical agent, galeterone (5). Concerns of potential in vivo stability of our recently discovered more efficacious galeterone 3β-imidazole carbamate (6) led to the design and synthesis of new steroidal compounds. Two of the 11 compounds, 3β-pyridyl ether (8) and 3β-imidazole (17) with antiproliferative GI50 values of 3.24 and 2.54 μM against CWR22Rv1 prostate cancer cell, are 2.75- and 3.5-fold superior to 5. In addition, compounds 8 and 17 possess improved (∼4-fold) AR-V7 degrading activities. Importantly, these two compounds are expected to be metabolically stable, making them suitable for further development as new therapeutics against all forms of prostate cancer. PMID:27437082

  8. Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

    Science.gov (United States)

    Nieschlag, Eberhard; Vorona, Elena

    2015-09-01

    Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms. PMID:26373946

  9. 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

  10. Fitness supplements as a gateway substance for anabolic-androgenic steroid use.

    Science.gov (United States)

    Hildebrandt, Tom; Harty, Seth; Langenbucher, James W

    2012-12-01

    Approximately 3.0% of young Americans have used anabolic-androgenic steroids (AAS). A traditional model of adolescent substance use, the gateway hypothesis, suggests that drug use follows a chronological, causal sequence, whereby initial use of a specific drug leads to an increased likelihood of future drug use. Therefore, the use of illicit appearance and performance enhancing drugs (APED), such as AASs, also follows an analogous progression, whereby legal APEDs, (e.g., nutritional supplements) precedes illicit APED use. We examined the relationship between nutritional supplement use, beliefs about APEDs, and APED use in 201 male (n = 100) and female (n = 101) undergraduates. Participants completed measures of muscle dysmorphia (MDDI), body checking (BCQ, MBCQ), eating disorder symptoms (EDE-Q), perfectionism (FMPS), positive beliefs about the efficacy-safety of AAS use and APED use patterns. A series of covariance structure models (CSM) showed body image disturbance, compulsive exercise, illicit drug use, and perfectionism, independent of gender, were significant predictors of positive beliefs about AAS. Those who used both fat burning and muscle building supplements reported the strongest beliefs in AAS efficacy-safety, which was associated with higher likelihood of current illicit APED use. There was evidence of significant indirect relationships between supplement use and illicit APED use through contact with other AAS users and beliefs about AAS. The potential role for nutritional supplement use in the initiation of illegal APED use is discussed. Future prevention efforts may benefit from targeting legal APED users in youth. PMID:22486333

  11. Anabolic-androgenic steroids and appetitive sexual behavior in male rats.

    Science.gov (United States)

    Kim, Jessica Y; Wood, Ruth I

    2014-09-01

    Anabolic-androgenic steroids (AAS) increase libido and sexual behavior, but the underlying behavioral mechanisms are unclear. One way AAS may enhance expression of sexual behavior is by increasing the willingness to work for sex. In the present study, sexually-experienced male rats received daily injections of testosterone at supraphysiologic doses (7.5 mg/kg in water with 13% cyclodextrin) or vehicle and were tested for appetitive sexual behavior measured by operant responding for access to an estrous female. Initially, rats were trained in their home cage to respond on a nose-poke under a 10-min fixed-interval schedule for food reward. Once rats achieved stable response rates, the food was replaced by a female, followed by mating for 10 min. There was no effect of testosterone on operant responding for food (28.1 ± 4.4 responses/10 min for testosterone, 30.6 ± 4.3 for vehicle) or sex (35.0 ± 4.0 responses/10 min for testosterone, 37.3 ± 5.2 for vehicle). However, rats made significantly more responses for sex than for food (p 0.05). These findings suggest that chronic high-dose testosterone does not enhance appetitive drive for sexual behavior. PMID:25200201

  12. The Cutaneous Bacterial Microflora of the Bodybuilders Using Anabolic-Androgenic Steroids

    Science.gov (United States)

    Zomorodian, Kamiar; Rahimi, Mohammad Javad; Taheri, Mohammad; Ghanbari Asad, Ali; Khani, Soghra; Ahrari, Iman; Pakshir, Keyvan; Khashei, Reza

    2014-01-01

    Background: Anabolic-androgenic steroids (AAS) abuse by the athletes has dramatically increased during the recent decades. These substances might increase the skin lipids and enhance the cutaneous microbial proliferation. Objectives: The current study aimed to investigate the potential side effects of AAS on the bacterial microflora colonization of the bodybuilders` skin. Patients and Methods: The skin samples of 94 male bodybuilders (71 AAS users, 23 non-AAS users) and 46 subjects of the control group, with similar gender and age, were cultured and incubated in both aerobic condition to isolate Staphylococcus aureus and anaerobic condition for Propionibacterium acnes. The isolated bacteria were identified by standard microbiological techniques. Results: The skin lesions were more frequent in the body builders than the controls. Moreover, statistically significant differences were also observed in skin lesions among the AAS users and the non-AAS user athletes. The prevalence of S. aureus and P. acnes in the athletes was higher than that of the control group. In addition, there was a significant difference in distribution of P. acnes between the bodybuilders who used AAS and those who did not. Conclusions: A higher number of bacterial flora was found in the bodybuilders particularly those using AAS in comparison to the controls, which might be due to the influence of these AAS on the skin microflora and transmission of the bacteria through the direct contact of the naked skin with the exercise instruments. PMID:25789120

  13. Aggression Is Associated With Increased Anabolic-Androgenic Steroid Use Contemplation Among Adolescents.

    Science.gov (United States)

    Sagoe, Dominic; Mentzoni, Rune A; Hanss, Daniel; Pallesen, Ståle

    2016-09-18

    We investigated the relationship between aggression and anabolic-androgenic steroid (AAS) use intent among adolescents. A nationally representative sample of Norwegian 18-year-olds (N = 1,334, females = 58.7%) took part in a survey in 2013 (response rate = 64.9%). Participants completed the physical and verbal subscales of the Short-Form Buss-Perry Aggression Questionnaire, the Intent to use AAS Scale, the Alcohol Use Disorders Identification Test-Consumption, and the Hospital Anxiety and Depression Scale. They also provided demographic information and answered questions about AAS use, gambling participation, as well as cigarette and snus use. Descriptive statistics and multinomial logistic regression were used to analyze the data. Lifetime and past year prevalence of AAS use was 0.1%. Between 0.4% and 1.7% of participants disclosed intent to use while between 1.1% and 2.5% expressed neutral intent to initiate AAS use. Compared to persons low on aggression, individuals high on aggression were more likely to report intent and curiosity towards initiating AAS use. Our findings indicate that aggression is a risk factor for AAS use contemplation among adolescents.

  14. 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.

  15. Anabolic-androgenic steroids and decision making: Probability and effort discounting in male rats.

    Science.gov (United States)

    Wallin, Kathryn G; Alves, Jasmin M; Wood, Ruth I

    2015-07-01

    Anabolic-androgenic steroid (AAS) abuse is implicated in maladaptive behaviors such as increased aggression and risk taking. Impaired judgment due to changes in the mesocorticolimbic dopamine system may contribute to these behavioral changes. While AAS are known to influence dopamine function in mesocorticolimbic circuitry, the effects on decision making are unknown. This was the focus of the present study. Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5 mg/kg) or vehicle (13% cyclodextrin in water), and tested for cost/benefit decision making in two discounting paradigms. Rats chose between a small reward (1 sugar pellet) and a large discounted reward (3 or 4 pellets). Probability discounting (PD) measures sensitivity to reward uncertainty by decreasing the probability (100, 75, 50, 25, 0%) of receiving the large reward in successive blocks of each daily session. Effort discounting (ED) measures sensitivity to a work cost by increasing the lever presses required to earn the large reward (1, 2, 5, 10, 15 presses). In PD, testosterone-treated rats selected the large/uncertain reward significantly less than vehicle-treated controls. However, during ED, testosterone-treated rats selected the large/high effort reward significantly more than controls. These studies show that testosterone has divergent effects on different aspects of decision making. Specifically, testosterone increases aversion to uncertainty but decreases sensitivity to the output of effort for reward. These results have implications for understanding maladaptive behavioral changes in human AAS users.

  16. Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

    Science.gov (United States)

    Nieschlag, Eberhard; Vorona, Elena

    2015-09-01

    Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

  17. What can allostasis tell us about anabolic-androgenic steroid addiction?

    Science.gov (United States)

    Hildebrandt, Tom; Yehuda, Rachel; Alfano, Lauren

    2011-08-01

    Anabolic-androgenic steroids (AASs) are synthetic hormones used by individuals who want to look better or perform better in athletics and at the gym. Their use raises an interesting paradox in which drug use is associated with a number of health benefits, but also the possibility of negative health consequences. Existing models of AAS addiction follow the traditional framework of drug abuse and dependence, which suggest that harmful use occurs as a result of the drug's ability to hijack the motivation-reward system. However, AASs, unlike typical drugs of abuse, are not used for acute intoxication effects or euphoria. Rather, AASs are used to affect the body through changes to the musculoskeletal system and the hypothalamic-pituitary-gonadal axis as opposed to stimulating the reward system. We offer an allostatic model of AAS addiction to resolve this inconsistency between traditional drug addiction and AAS addiction. This allostatic framework provides a way to (a) incorporate exercise into AAS misuse, (b) identify where AAS use transitions from recreational use into a drug problem, and (c) describe individual differences in vulnerability or resilience to AASs. Implications for this model of AAS addiction are discussed. PMID:21756441

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

    Directory of Open Access Journals (Sweden)

    Rafael Areas Vargas

    2013-09-01

    Full Text Available Purpose 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. Materials and 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 < 0.05 was considered significant. Results: The weight (p < 0.001 and volume (p = 0.004 of the prostate ventral lobe showed differences between C65 and T65 groups and between C105 and T105 groups. The epithelium height showed no difference between groups C65 and T65 (p = 0.8509, but the T105 group showed an increase of 32% compared to C105 (p = 0.0089. Concerning

  19. Androgens.

    Science.gov (United States)

    Iyer, Rakesh; Handelsman, David J

    2016-01-01

    Androgen abuse is the most potent and prevalent form of sports doping detected. It originated from the early years of the Cold War as an epidemic confined to drug cheating within elite power sports. In the decades following the end of the Cold War, it has become disseminated into an endemic based within the illicit drug subcultures serving recreational abusers seeking cosmetic body sculpting effects. Within sports, both direct androgen abuse (administration of androgens), as well as indirect androgen abuse (administration of nonandrogenic drugs to increase endogenous testosterone), is mostly readily detectable with mass spectrometry-based anti-doping urine tests. The ongoing temptation of fame and fortune and the effectiveness of androgen abuse in power sports continue to entice cheating via renewed approaches aiming to exploit androgens. These require ongoing vigilance, inventiveness in anti-doping science, and targeting coaches as well as athletes in order to build resilience against doping and maintain fairness in elite sport. The challenge of androgen abuse in the community among recreational abusers has barely been recognized and effective approaches remain to be developed. PMID:27347677

  20. Steroids

    Science.gov (United States)

    ... steroids (say: STARE-oydz), they often mean illegal anabolic steroids. Anabolic steroids are artificially produced hormones that are the same ... these is testosterone (say: tes-TOSS-tuh-rone). Anabolic steroids can be taken in the form of pills, ...

  1. Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats.

    Science.gov (United States)

    Roşca, A E; Stoian, I; Badiu, C; Gaman, L; Popescu, B O; Iosif, L; Mirica, R; Tivig, I C; Stancu, C S; Căruntu, C; Voiculescu, S E; Zăgrean, L

    2016-01-01

    Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

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

    Directory of Open Access Journals (Sweden)

    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.

  3. A preliminary MTD-PLS study for androgen receptor binding of steroid compounds

    Science.gov (United States)

    Bora, Alina; Seclaman, E.; Kurunczi, L.; Funar-Timofei, Simona

    The relative binding affinities (RBA) of a series of 30 steroids for Human Androgen Receptor (AR) were used to initiate a MTD-PLS study. The 3D structures of all the compounds were obtained through geometry optimization in the framework of AM1 semiempirical quantum chemical method. The MTD hypermolecule (HM) was constructed, superposing these structures on the AR-bonded dihydrotestosterone (DHT) skeleton obtained from PDB (AR complex, ID 1I37). The parameters characterizing the HM vertices were collected using: AM1 charges, XlogP fragmental values, calculated fragmental polarizabilities (from refractivities), volumes, and H-bond parameters (Raevsky's thermodynamic originated scale). The resulted QSAR data matrix was submitted to PCA (Principal Component Analysis) and PLS (Projections in Latent Structures) procedure (SIMCA P 9.0); five compounds were selected as test set, and the remaining 25 molecules were used as training set. In the PLS procedure supplementary chemical information was introduced, i.e. the steric effect was always considered detrimental, and the hydrophobic and van der Waals interactions were imposed to be beneficial. The initial PLS model using the entire training set has the following characteristics: R2Y = 0.584, Q2 = 0.344. Based on distances to the model criterions (DMODX and DMODY), five compounds were eliminated and the obtained final model had the following characteristics: R2Y D 0.891, Q2 D 0.591. For this the external predictivity on the test set was unsatisfactory. A tentative explanation for these behaviors is the weak information content of the input QSAR matrix for the present series comparatively with other successful MTD-PLS modeling published elsewhere.

  4. Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

    Science.gov (United States)

    Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

    2015-06-01

    Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected.

  5. Neurotoxicity by synthetic androgen steroids: oxidative stress, apoptosis, and neuropathology: A review.

    Science.gov (United States)

    Pomara, Cristoforo; Neri, Margherita; Bello, Stefania; Fiore, Carmela; Riezzo, Irene; Turillazzi, Emanuela

    2015-01-01

    Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS - induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future. PMID:26074748

  6. 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.

  7. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    Science.gov (United States)

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure. PMID:26691962

  8. 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)

  9. High-throughput analysis of 19 endogenous androgenic steroids by ultra-performance convergence chromatography tandem mass spectrometry.

    Science.gov (United States)

    Quanson, Jonathan L; Stander, Marietjie A; Pretorius, Elzette; Jenkinson, Carl; Taylor, Angela E; Storbeck, Karl-Heinz

    2016-09-15

    11-Oxygenated steroids such as 11-ketotestosterone and 11-ketodihydrotestosterone have recently been shown to play a putative role in the development and progression of castration resistant prostate cancer. In this study we report on the development of a high throughput ultra-performance convergence chromatography tandem mass spectrometry (UPC(2)-MS/MS) method for the analysis of thirteen 11-oxygenated and six canonical C19 steroids isolated from a cell culture matrix. Using an Acquity UPC(2) BEH 2-EP column we found that UPC(2) resulted in superior selectivity, increased chromatographic efficiency and a scattered elution order when compared to conventional reverse phase ultra-performance liquid chromatography (UPLC). Furthermore, there was a significant improvement in sensitivity (5-50 times). The lower limits of quantification ranged between 0.01-10ngmL(-1), while the upper limit of quantification was 100ngmL(-1) for all steroids. Accuracy, precision, intra-day variation, recovery, matrix effects and process efficiency were all evaluated and found to be within acceptable limits. Taken together we show that the increased power of UPC(2)-MS/MS allows the analyst to complete in vitro assays at biologically relevant concentrations for the first time and in so doing determine the routes of steroid metabolism which is vital for studies of androgen responsive cancers, such as prostate cancer, and could highlight new mechanisms of disease progression and new targets for cancer therapy. PMID:27479683

  10. 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.

  11. 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)

  12. A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens

    NARCIS (Netherlands)

    J. Veldscholte (Jos); C. Ris-Stalpers (Carolyn); G.G.J.M. Kuiper (George); G.W. Jenster (Guido); C.A. Berrevoets (Cor); H.J.H.M. Claassen (Eric); H.C.J. van Rooij (Henri); J. Trapman (Jan); A.O. Brinkmann (Albert); E. Mulder (Eppo)

    1990-01-01

    markdownabstractAbstract INCaP prostate tumor cells contain an abnormal androgen receptor system. Progestagens, estradiol and anti-androgens can compete with androgens for binding to the androgen receptor and can stimulate both cell growth and excretion of prostate specific acid phosphatase. We ha

  13. Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.

    Science.gov (United States)

    Hines, Melissa; Pasterski, Vickie; Spencer, Debra; Neufeld, Sharon; Patalay, Praveetha; Hindmarsh, Peter C; Hughes, Ieuan A; Acerini, Carlo L

    2016-02-19

    Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. PMID:26833843

  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. 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)

  16. Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors.

    Science.gov (United States)

    Cai, Changmeng; Chen, Sen; Ng, Patrick; Bubley, Glenn J; Nelson, Peter S; Mostaghel, Elahe A; Marck, Brett; Matsumoto, Alvin M; Simon, Nicholas I; Wang, Hongyun; Chen, Shaoyong; Balk, Steven P

    2011-10-15

    Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen deprivation therapy of primary prostate cancer can be mediated by reactivation of the androgen receptor (AR). One important mechanism mediating this AR reactivation is intratumoral conversion of the weak adrenal androgens DHEA and androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA and androstenedione are synthesized by the adrenals through the sequential actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC. However, the significance of intratumoral CYP17A1 and de novo androgen synthesis from cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor resistance/relapse, remain to be determined. We report that AR activity in castration-resistant VCaP tumor xenografts can be restored through CYP17A1-dependent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes selective pressure for increased intratumoral expression of CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1 inhibitors. Supporting the clinical relevance of this mechanism, we found that intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent, but that AR activity in these cells is still steroid dependent and mediated by upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis. Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may remain steroid dependent and therefore responsive to therapies that can further suppress de novo intratumoral steroid synthesis.

  17. The Misuse of Anabolic-Androgenic Steroids among Iranian Re-crea¬tional Male Body-Builders and Their Related Psycho-So¬cio-Demographic factors

    OpenAIRE

    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...

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

    OpenAIRE

    Barker James; Székely Andrea D; Petróczi Andrea; Deshmukh Nawed; Hussain Iltaf; Naughton Declan P

    2010-01-01

    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...

  19. Acute kidney injury associated with androgenic steroids and nutritional supplements in bodybuilders†

    Science.gov (United States)

    Almukhtar, Safa E.; Abbas, Alaa A.; Muhealdeen, Dana N.; Hughson, Michael D.

    2015-01-01

    Four bodybuilders who injected anabolic steroids and ingested commercial protein (78–104 g/day) and creatine (15 g/day) products presented with serum creatinine levels between 229.84 and 335.92 µmol/L (2.6–3.8 mg/dL). Renal biopsies revealed acute tubular necrosis. Four weeks after discontinuing injections and supplements, serum creatinine was in the normal range and estimated glomerular filtration rate > 1.00 mL/s (60 mL/min), including two patients with biopsies showing >30% interstitial fibrosis and tubular atrophy. The findings highlight a risk for acute and potentially chronic kidney injury among young men abusing anabolic steroids and using excessive amounts of nutritional supplements. PMID:26251708

  20. Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: Evidence for further genetic heterogeneity in this syndrome

    International Nuclear Information System (INIS)

    The cloning of a cDNA for the human androgen receptor gene has resulted in the availability for cDNA probes that span various parts of the gene, including the entire steroid-binding domain and part of the DNA-binding domain, as well as part of the 5' region of the gene. The radiolabeled probes were used to screen for androgen receptor mutations on Southern blots prepared by restriction endonuclease digestion of genomic DNA from human subjects with complete androgen insensitivity syndrome (AIS). In this investigation, the authors considered only patients presenting complete AIS and with the androgen receptor (-) form as the most probably subjects to show a gene deletion. One subject from each of six unrelated families with the receptor (-) form of complete AIS and 10 normal subjects were studied. In the 10 normal subjects and in 5 of the 6 patients, identical DNA restriction fragment patterns were observed with EcoRI and BamHI. Analysis of other members of this family confirmed the apparent gene deletion. The data provide direct proof that complete AIS in some families can result from a deletion of the androgen receptor structural gene. However, other families do not demonstrate such a deletion, suggesting that point mutations may also result in the receptor (-) form of complete AIS, adding further to the genetic heterogeneity of this syndrome

  1. Dissection of androgen receptor-promoter interactions: steroid receptors partition their interaction energetics in parallel with their phylogenetic divergence.

    Science.gov (United States)

    De Angelis, Rolando W; Yang, Qin; Miura, Michael T; Bain, David L

    2013-11-15

    Steroid receptors comprise a homologous family of ligand-activated transcription factors. The members include androgen receptor (AR), estrogen receptor (ER), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and progesterone receptor (PR). Phylogenetic studies demonstrate that AR, GR, MR, and PR are most closely related, falling into subgroup 3C. ER is more distantly related, falling into subgroup 3A. To determine the quantitative basis by which receptors generate their unique transcriptional responses, we are systematically dissecting the promoter-binding energetics of all receptors under a single "standard state" condition. Here, we examine the self-assembly and promoter-binding energetics of full-length AR and a mutant associated with prostate cancer, T877A. We first demonstrate that both proteins exist only as monomers, showing no evidence of dimerization. Although this result contradicts the traditional understanding that steroid receptors dimerize in the absence of DNA, it is fully consistent with our previous work demonstrating that GR and two PR isoforms either do not dimerize or dimerize only weakly. Moreover, both AR proteins exhibit substantial cooperativity between binding sites, again as seen for GR and PR. In sharp contrast, the more distantly related ER-α dimerizes so strongly that energetics can only be measured indirectly, yet cooperativity is negligible. Thus, homologous receptors partition their promoter-binding energetics quite differently. Moreover, since receptors most closely related by phylogeny partition their energetics similarly, such partitioning appears to be evolutionarily conserved. We speculate that such differences in energetics, coupled with different promoter architectures, serve as the basis for generating receptor-specific promoter occupancy and thus function.

  2. 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.

  3. Modulation of the cytosolic androgen receptor in striated muscle by sex steroids

    Science.gov (United States)

    Rance, N. E.; Max, S. R.

    1984-01-01

    The effects of orchiectomy (GDX) and of subsequent administration of testosterone propionate (TP) or 17(beta)-estradiol (E2) on the maximum binding (Bmax) and apparent Kd of the cytosolic androgen receptor in levator ani (LA) and skeletal muscles of adult male Sprague-Dawley rats are investigated experimentally. The results are presented in graphs and discussed. In LA, BMAX is found to rise from a control level of 2.5 fmol/mg protein to 280, 600, 478, and 133 percent of control at 12 h, 14 d, 30 d, and 44 d after GDX, respectively, while Kd increased only insignificantly (from 680 to 960 fM); Bmax is held at control levels for 6 h by cycloheximide given at GDX, is unaffected by TP given at 30 d, and is further increased (by 480 percent at 44 d) by administration of E2 at 30 d. Bmax in skeletal muscles is found to increase to 139, 212, 220, and 158 percent of control at 12 h, 14 d, 30 d, and 44 d, respectively; Bmax is returned to control at 44 d by TP at 30 d but is not affected by E2. The effect of E2 in LA is attributed to either induction of the cytosolic receptor or a decreased rate of receptor degradation.

  4. Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma.

    Science.gov (United States)

    Caruso, Donatella; Abbiati, Federico; Giatti, Silvia; Romano, Simone; Fusco, Letizia; Cavaletti, Guido; Melcangi, Roberto Cosimo

    2015-02-01

    Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3α-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An increase of PREG, T, 3α-diol, 3β-diol and 17β-estradiol was associated with decreased levels of DHP and THP. The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment. This article is part of a Special Issue entitled 'Sex steroids and brain disorders'. PMID:24717976

  5. Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

    Science.gov (United States)

    Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

    2000-01-01

    We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

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

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    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.

  7. [Artificial illness as a result of non-medical use of anabolic androgenic steroids: A case report and a review of literature].

    Science.gov (United States)

    Povzun, S A

    2016-01-01

    A 42-year-old female body builder who had used anabolic androgenic steroids (AASs) for 18 years to build up muscle mass died from liver rupture. The cause of the latter was multiple abscesses caused by Actinomyces, which developed in the presence of immunodeficiency. The postmortem changes in different organs were due to hormonal imbalance. The paper gives the data available in the literature pertaining to the analysis of the effects of AASs taken in supraphysiological doses on the body and their non-medical application.

  8. 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.

  9. 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. PMID:25026387

  10. [Artificial illness as a result of non-medical use of anabolic androgenic steroids: A case report and a review of literature].

    Science.gov (United States)

    Povzun, S A

    2016-01-01

    A 42-year-old female body builder who had used anabolic androgenic steroids (AASs) for 18 years to build up muscle mass died from liver rupture. The cause of the latter was multiple abscesses caused by Actinomyces, which developed in the presence of immunodeficiency. The postmortem changes in different organs were due to hormonal imbalance. The paper gives the data available in the literature pertaining to the analysis of the effects of AASs taken in supraphysiological doses on the body and their non-medical application. PMID:27600782

  11. Rarity of DNA sequence alterations in the promoter region of the human androgen receptor gene

    Directory of Open Access Journals (Sweden)

    D.F. Cabral

    2004-12-01

    Full Text Available The human androgen receptor (AR gene promoter lies in a GC-rich region containing two principal sites of transcription initiation and a putative Sp1 protein-binding site, without typical "TATA" and "CAAT" boxes. It has been suggested that mutations within the 5'untranslated region (5'UTR may contribute to the development of prostate cancer by changing the rates of gene transcription and/or translation. In order to investigate this question, the aim of the present study was to search for the presence of mutations or polymorphisms at the AR-5'UTR in 92 prostate cancer patients, where histological diagnosis of adenocarcinoma was established in specimens obtained from transurethral resection or after prostatectomy. The AR-5'UTR was amplified by PCR from genomic DNA samples of the patients and of 100 healthy male blood donors, included as controls. Conformation-sensitive gel electrophoresis was used for DNA sequence alteration screening. Only one band shift was detected in one individual from the blood donor group. Sequencing revealed a new single nucleotide deletion (T in the most conserved portion of the promoter region at position +36 downstream from the transcription initiation site I. Although the effect of this specific mutation remains unknown, its rarity reveals the high degree of sequence conservation of the human androgen promoter region. Moreover, the absence of detectable variation within the critical 5'UTR in prostate cancer patients indicates a low probability of its involvement in prostate cancer etiology.

  12. 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

  13. 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

  14. Androgen regulates neuritin mRNA levels in an in vivo model of steroid-enhanced peripheral nerve regeneration.

    Science.gov (United States)

    Fargo, Keith N; Alexander, Thomas D; Tanzer, Lisa; Poletti, Angelo; Jones, Kathryn J

    2008-05-01

    Following crush injury to the facial nerve in Syrian hamsters, treatment with androgens enhances axonal regeneration rates and decreases time to recovery. It has been demonstrated in vitro that the ability of androgen to enhance neurite outgrowth in motoneurons is dependent on neuritin-a protein that is involved in the re-establisment of neuronal connectivity following traumatic damage to the central nervous system and that is under the control of several neurotrophic and neuroregenerative factors--and we have hypothesized that neuritin is a mediator of the ability of androgen to increase peripheral nerve regeneration rates in vivo. Testosterone treatment of facial nerve-axotomized hamsters resulted in an approximately 300% increase in neuritin mRNA levels 2 days post-injury. Simultaneous treatment with flutamide, an androgen receptor blocker that is known to prevent androgen enhancement of nerve regeneration, abolished the ability of testosterone to upregulate neuritin mRNA levels. In a corroborative in vitro experiment, the androgen dihydrotestosterone induced an approximately 100% increase in neuritin mRNA levels in motoneuron-neuroblastoma cells transfected with androgen receptors, but not in cells without androgen receptors. These data confirm that neuritin is under the control of androgens, and suggest that neuritin is an important effector of androgen in enhancing peripheral nerve regeneration following injury. Given that neuritin has now been shown to be involved in responses to both central and peripheral injuries, and appears to be a common effector molecule for several neurotrophic and neurotherapeutic agents, understanding the neuritin pathway is an important goal for the clinical management of traumatic nervous system injuries. PMID:18419250

  15. 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

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

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    Halldorsson Vidar

    2010-12-01

    Full Text Available Abstract Background 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. Method We use logistic regression and predicted probabilities to analyze data from a national representative survey of 11031 Icelandic high school students. Results 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. Conclusion 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

  17. Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess.

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    Adam F Summers

    Full Text Available Aspiration of bovine follicles 12-36 hours after induced corpus luteum lysis serendipitously identified two populations of cows, one with High androstenedione (A4; >40 ng/ml; mean = 102 and another with Low A4 (<20 ng/ml; mean = 9 in follicular fluid. We hypothesized that the steroid excess in follicular fluid of dominant follicles in High A4 cows would result in reduced fertility through altered follicle development and oocyte maternal RNA abundance. To test this hypothesis, estrous cycles of cows were synchronized and ovariectomy was performed 36 hours later. HPLC MS/MS analysis of follicular fluid showed increased dehydroepiandrosterone (6-fold, A4 (158-fold and testosterone (31-fold in the dominant follicle of High A4 cows. However, estrone (3-fold and estradiol (2-fold concentrations were only slightly elevated, suggesting a possible inefficiency in androgen to estrogen conversion in High A4 cows. Theca cell mRNA expression of LHCGR, GATA6, CYP11A1, and CYP17A1 was greater in High A4 cows. Furthermore, abundance of ZAR1 was decreased 10-fold in cumulus oocyte complexes from High A4 cows, whereas NLRP5 abundance tended to be 19.8-fold greater (P = 0.07. There was a tendency for reduction in stage 4 follicles in ovarian cortex samples from High A4 cows suggesting that progression to antral stages were impaired. High A4 cows tended (P<0.07 to have a 17% reduction in calving rate compared with Low A4 cows suggesting reduced fertility in the High A4 population. These data suggest that the dominant follicle environment of High A4 cows including reduced estrogen conversion and androgen excess contributes to infertility in part through altered follicular and oocyte development.

  18. 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

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    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.

  19. 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 (steroids naturally present in urine of untreated horses (mares and geldings).

  20. 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

  1. Prenatal exposure to di-n-butyl phthalate (DBP) differentially alters androgen cascade in undeformed versus hypospadiac male rat offspring.

    Science.gov (United States)

    Jiang, Jun-Tao; Zhong, Chen; Zhu, Yi-Ping; Xu, Dong-Liang; Wood, Kristofer; Sun, Wen-Lan; Li, En-Hui; Liu, Zhi-Hong; Zhao, Wei; Ruan, Yuan; Xia, Shu-Jie

    2016-06-01

    This study was to compare the alterations of androgen cascades in di-n-butyl phthalate (DBP)-exposed male offspring without hypospadias (undeformed) versus those with hypospadias. To induce hypospadias in male offspring, pregnant rats received DBP via oral gavage at a dose of 750mg/kg BW/day during gestational days 14-18. The mRNA expression levels of genes downstream of the androgen signaling pathway, such as androgen receptor (AR) and Srd5a2, in testes of undeformed rat pups were similar to those in controls; in hypospadiac rat pups these levels were significantly lower than those of control pups. In contrast, both undeformed and hypospadiac rats had decreased serum testosterone levels, reduced mRNA expression of key enzymes in the androgen synthetic pathway in the testes, and ablated genes of developmental pathways, such as Shh, Bmp4, Fgf8, Fgf10 and Fgfr2, in the genital tubercle (GT) as compared to those in DBP-unexposed controls, albeit hypospadiac rats had a more severe decrement than those of undeformed rats. Although other possibilities cannot be excluded, our findings suggest that the relatively normal levels of testosterone-AR-Srd5a2 may contribute to the resistance to DBP toxicity in undeformed rats. In conclusion, our results showed a potential correlation between decreased testosterone levels, reduced mRNA expression of AR and Srd5a2 and the occurrence of hypospadias in male rat offspring prenatally exposed to DBP. PMID:26948521

  2. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)

    1991-01-01

    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of t

  3. Reptides and Proteins Interacting with the Androgen Receptor

    NARCIS (Netherlands)

    D.J. van de Wijngaart (Dennis)

    2009-01-01

    textabstractAndrogens are important sex steroid hormones. The androgens testosterone and dihydrotestosterone (DHT) are essential for normal male sexual differentiation and for the development and maintenance of male reproductive tissues, including the prostate. Androgens mediate their effects by bin

  4. 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.

  5. PROGRESSION TO ANDROGEN-INDEPENDENT LNCAP HUMAN PROSTATE TUMORS: CELLULAR AND MOLECULAR ALTERATIONS

    OpenAIRE

    Zhou, Jin-Rong; Yu, Lunyin; Zerbini, Luiz F.; Libermann, Towia A.; Blackburn, George L.

    2004-01-01

    Lethal phenotypes of human prostate cancer are characterized by progression to androgen-independence and metastasis. For want of a clinically relevant animal model, mechanisms behind this progression remain unclear. Our study used an in vivo model of androgen-sensitive LNCaP human prostate cancer cell xenografts in male SCID mice to study the cellular and molecular biology of tumor progression. Primary tumors were established orthotopically, and the mice were then surgically castrated to with...

  6. Steroid hormone synthetic pathways in prostate cancer.

    Science.gov (United States)

    Mostaghel, Elahe A

    2013-09-01

    While androgen deprivation therapy (ADT) remains the primary treatment for metastatic prostate cancer (PCa) since the seminal recognition of the disease as androgen-dependent by Huggins and Hodges in 1941, therapy is uniformly marked by progression to castration-resistant prostate cancer (CRPC) over a period of about 18 months, with an ensuing median survival of 1 to 2 years. Importantly, castration does not eliminate androgens from the prostate tumor microenvironment. Castration resistant tumors are characterized by elevated tumor androgens that are well within the range capable of activating the AR and AR-mediated gene expression, and by steroid enzyme alterations which may potentiate de novo androgen synthesis or utilization of circulating adrenal androgens. The dependence of CRPC on intratumoral androgen metabolism has been modeled in vitro and in vivo, and residual intratumoral androgens are implicated in nearly every mechanism by which AR-mediated signaling promotes castration-resistant disease. These observations suggest that tissue based alterations in steroid metabolism contribute to the development of CRPC and underscore these metabolic pathways as critical targets of therapy. Herein, we review the accumulated body of evidence which strongly supports intracrine (tumoral) androgen synthesis as an important mechanism underlying PCa progression. We first discuss the presence and significance of residual prostate tumor androgens in the progression of CRPC. We review the classical and non-classical pathways of androgen metabolism, and how dysregulated expression of these enzymes is likely to potentiate tumor androgen production in the progression to CRPC. Next we review the in vitro and in vivo data in human tumors, xenografts, and cell line models which demonstrate the capacity of prostate tumors to utilize cholesterol and adrenal androgens in the production of testosterone (T) and dihydrotestosterone (DHT), and briefly review the potential role of exogenous

  7. 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.

  8. Anemarrhena asphodeloides Non-Steroidal Saponin Components Alter the Pharmacokinetic Profile of Its Steroidal Saponins in Rat

    OpenAIRE

    Zhishu Tang; Guolong Li; Jie Yang; Jinao Duan; Dawei Qian; Jianming Guo; Zhenhua Zhu; Zhongxing Song

    2015-01-01

    A rapid, selective and sensitive UPLC-MS/MS assay was established to determine the plasma concentrations of four steroidal saponins. Sprague-Dawley rats were allocated to four groups which were orally administered Anemarrhena asphodeloides extracts (ASE), ASE combined with macromolecular fraction (ASE-MF), ASE combined with small molecule fraction (ASE-SF) and ASE combined with small molecule and macromolecular fraction (ASE-SF-MF) containing approximately the same dose of ASE. At different t...

  9. Effective separation and simultaneous analysis of anabolic androgenic steroids (AAS in their pharmaceutical formulations by a validated TLC-densitometry method

    Directory of Open Access Journals (Sweden)

    Musharraf Syed

    2012-06-01

    Full Text Available Abstract Background Anabolic androgenic steroids (AAS are widely misused for the enhancement of performance in sports. Several drugs are available that contain different combinations or individual steroids in different dosage form. This paper describes a TLC densitometric method for simultaneous determination of four AAS of testosterone derivatives including testosterone propionate (TP, testosterone phenyl propionate (TPP, testosterone isocaproate (TI and testosterone deaconate (TD in their pharmaceutical products. Results Separation was carried out on Al based TLC plates, pre-coated with silica gel 60F-254 using hexane and ethyl acetate (8.5:1.5, v/v. Spots at Rf 0.31 ± 0.01, 0.34 ± 0.01, 0.40 ± 0.01 and 0.45 ± 0.02 were recognized as TPP, TP, TI and TD, respectively. Quantitative analysis was done by densitometric measurements at λmax 251 nm for all derivatives. The developed method was validated as per ICH guidelines. Method was found linear over the concentration range of 200–1200 ng/spot with the correlation coefficient of 0.995, 0.993, 0.995 and 0.996 for TP, TPP, TI, TD, respectively. Limit of detection for all derivatives were in the range of 16.7-22.3 ng/spot while limit of quantitation were found to be in the range of 55.7-70.9 ng/spot. Conclusions The developed TLC method can be applied for the simultaneous routine analysis of testosterone derivatives in their individual and combined pharmaceutical formulations.

  10. Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

    Directory of Open Access Journals (Sweden)

    Wang Fang

    2012-05-01

    Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

  11. Sexual Dimorphism in the Regulation of Estrogen, Progesterone, and Androgen Receptors by Sex Steroids in the Rat Airway Smooth Muscle Cells

    Science.gov (United States)

    Zarazúa, Abraham; González-Arenas, Aliesha; Ramírez-Vélez, Gabriela; Bazán-Perkins, Blanca; Guerra-Araiza, Christian; Campos-Lara, María G.

    2016-01-01

    The role of sex hormones in lung is known. The three main sex steroid receptors, estrogen, progesterone, and androgen, have not been sufficiently studied in airway smooth muscle cells (ASMC), and the sex hormone regulation on these receptors is unknown. We examined the presence and regulation of sex hormone receptors in female and male rat ASMC by Western blotting and flow cytometry. Gonadectomized rats were treated with 17β-estradiol, progesterone, 17β-estradiol + progesterone, or testosterone. ASMC were enzymatically isolated from tracheas and bronchi. The experiments were performed with double staining flow cytometry (anti-α-actin smooth muscle and antibodies to each hormone receptor). ERα, ERβ, tPR, and AR were detected in females or males. ERα was upregulated by E2 and T and downregulated by P4 in females; in males, ERα was downregulated by P4, E + P, and T. ERβ was downregulated by each treatment in females, and only by E + P and T in males. tPR was downregulated by P4, E + P, and T in females. No hormonal regulation was observed in male receptors. AR was downregulated in males treated with E + P and T. We have shown the occurrence of sex hormone receptors in ASMC and their regulation by the sex hormones in female and male rats. PMID:27110242

  12. Sexual Dimorphism in the Regulation of Estrogen, Progesterone, and Androgen Receptors by Sex Steroids in the Rat Airway Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Abraham Zarazúa

    2016-01-01

    Full Text Available The role of sex hormones in lung is known. The three main sex steroid receptors, estrogen, progesterone, and androgen, have not been sufficiently studied in airway smooth muscle cells (ASMC, and the sex hormone regulation on these receptors is unknown. We examined the presence and regulation of sex hormone receptors in female and male rat ASMC by Western blotting and flow cytometry. Gonadectomized rats were treated with 17β-estradiol, progesterone, 17β-estradiol + progesterone, or testosterone. ASMC were enzymatically isolated from tracheas and bronchi. The experiments were performed with double staining flow cytometry (anti-α-actin smooth muscle and antibodies to each hormone receptor. ERα, ERβ, tPR, and AR were detected in females or males. ERα was upregulated by E2 and T and downregulated by P4 in females; in males, ERα was downregulated by P4, E + P, and T. ERβ was downregulated by each treatment in females, and only by E + P and T in males. tPR was downregulated by P4, E + P, and T in females. No hormonal regulation was observed in male receptors. AR was downregulated in males treated with E + P and T. We have shown the occurrence of sex hormone receptors in ASMC and their regulation by the sex hormones in female and male rats.

  13. Fast and sensitive liquid chromatography-mass spectrometry assay for seven androgenic and progestagenic steroids in human serum.

    Science.gov (United States)

    Keski-Rahkonen, Pekka; Huhtinen, Kaisa; Poutanen, Matti; Auriola, Seppo

    2011-11-01

    A fast and sensitive LC-MS/MS method for the quantitative analysis of seven steroid hormones in 150 μl of human serum was developed and validated. The following compounds were included: 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, testosterone, pregnenolone, and progesterone. Individual stable isotope-labeled analogues were used as internal standards. Sample preparation was performed by liquid-liquid extraction, followed by oxime derivatization to improve the ionization efficiency of the analytes. In contrast to the common derivatization-based methods, the reaction was incorporated into the sample preparation process and the only additional step due to the derivatization was a short heating of the autosampler vials before the sample injection. Chromatographic separation was achieved on a reversed-phase column using a methanol-water gradient. For the analyte detection, a triple quadrupole instrument with electrospray ionization was used. Total run time was 7.0 min and the lower limits of quantification were in the range of 0.03-0.34 nM (0.01-0.10 ng/ml), depending on the analyte. The method was validated using human serum samples from both sexes and applied for the serum steroid profiling of endometriosis patients.

  14. 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

  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. Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability

    Directory of Open Access Journals (Sweden)

    Satu Ikonen

    2011-11-01

    Full Text Available Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis, and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol ([4-{2,6-di-tert-butyl-4-[(1-{[3-tert-butyl-4-hydroxy-5-(propan-2-ylphenyl]sulfanyl}ethylsulfanyl]phenoxy}-4-oxo-butanoic acid] possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, β-sitosterol and stigmasterol possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodrug was also prepared in order to enhance the absorption of succinobucol through the intestinal membrane into the organism and to target the drug into the place of lipid metabolism—The enterohepatic circulation system. Their low toxicity towards mice fibroblasts at maximal concentrations, their antioxidant activity, comparable or even higher than that of ascorbic acid as determined by direct quenching of the DPPH radical, and their potential for significantly altering total and LDL cholesterol levels, suggest that these conjugates merit further studies in the treatment of cardiovascular or other related diseases. A brief discussion of succinobucol’s ability to quench the radicals, supported with a computational model of the electrostatic potential mapped on the electron density surface of the drug, is also presented.

  17. Metabolic alteration of neuroactive steroids and protective effect of progesterone in Alzheimer’s disease-like rats

    Institute of Scientific and Technical Information of China (English)

    Sha Liu; Honghai Wu; Gai Xue; Xin Ma; Jie Wu; Yabin Qin; Yanning Hou

    2013-01-01

    A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta (Aβ) 25-35 (Aβ25-35) injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.

  18. Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Valerie W Hu

    Full Text Available Despite the identification of numerous autism susceptibility genes, the pathobiology of autism remains unknown. The present "case-control" study takes a global approach to understanding the molecular basis of autism spectrum disorders based upon large-scale gene expression profiling. DNA microarray analyses were conducted on lymphoblastoid cell lines from over 20 sib pairs in which one sibling had a diagnosis of autism and the other was not affected in order to identify biochemical and signaling pathways which are differentially regulated in cells from autistic and nonautistic siblings. Bioinformatics and gene ontological analyses of the data implicate genes which are involved in nervous system development, inflammation, and cytoskeletal organization, in addition to genes which may be relevant to gastrointestinal or other physiological symptoms often associated with autism. Moreover, the data further suggests that these processes may be modulated by cholesterol/steroid metabolism, especially at the level of androgenic hormones. Elevation of male hormones, in turn, has been suggested as a possible factor influencing susceptibility to autism, which affects approximately 4 times as many males as females. Preliminary metabolic profiling of steroid hormones in lymphoblastoid cell lines from several pairs of siblings reveals higher levels of testosterone in the autistic sibling, which is consistent with the increased expression of two genes involved in the steroidogenesis pathway. Global gene expression profiling of cultured cells from ASD probands thus serves as a window to underlying metabolic and signaling deficits that may be relevant to the pathobiology of autism.

  19. Androgens and Bone

    OpenAIRE

    Clarke, Bart L.; Khosla, Sundeep

    2008-01-01

    Testosterone is the major gonadal sex steroid produced by the testes in men. Testosterone is also produced in smaller amounts by the ovaries in women. The adrenal glands produce the weaker androgens dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. These androgens collectively affect skeletal homeostasis throughout life in both men and women, particularly at puberty and during adult life. Because testosterone can be metabolized to estradiol by the aromatase enzyme, ...

  20. 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

    2013-09-01

    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. PMID:23953207

  1. Androgenic-anabolic steroids and the Olympic Games%雄激素类固醇激素与奥运会

    Institute of Scientific and Technical Information of China (English)

    Kenneth D. Fitch

    2008-01-01

    Androgenic-anabolic steroids (AAS) have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republic(GDR) from 1965 to 1989 which assisted that country to win many medals at Olympic Games, especially in female events. Currently, AAS are the most frequent category of prohibited substances detected in the urine of athletes both globally and at the last two Summer Olympic Games. Scientific confirmation that AAS are effective in enhancing sports performance was difficult because ethical approval was difficult for research involving male subjects taking massive doses of androgens as some athletes and bodybuilders did. Methods to detect AAS have evolved gradually over the past three decades and currently, despite an impressive array of sophisticated analytical equipment and methods, anti-doping authorities and analytical scientists continue to face challenges as have occurred from the use by athletes of designer AAS during the past few years. The future development and use of selective androgen receptor modulators (SARMs) can be anticipated to pose problems in the years ahead. Endocrinologists should be aware that on occasions, replacement testosterone (T) therapy may be authorized in sport as a therapeutic use exemption (TUE)and these circumstances are discussed.%即使在1974年被禁用后,雄激素类固醇激素(AAS)仍然一直被参加奥运会的运动员滥用.掺杂有AAS的药物于1965年到1989年之间出现在德意志民主共和国(GDR),这些药物帮助GDR在奥运会上赢得了许多奖牌,尤其在女子项目上.AAS是目前在全世界和近两届夏季奥运会上在运动员尿检中检测到的最常见的违禁药物.获得科学证据证实AAS提高运动成绩的有效性是十分困难的,因为在研究工作中让男性实验者服用某些运动员和健美人士服用的大剂量的雄激素是很难获得伦理学批准

  2. 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

    2016-02-01

    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. PMID:26772132

  3. 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.

  4. The Misuse of Anabolic-Androgenic Steroids among Iranian Re-crea¬tional Male Body-Builders and Their Related Psycho-So¬cio-Demographic factors

    Directory of Open Access Journals (Sweden)

    Hooman ANGOORANI

    2015-12-01

    Full Text Available 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. Keywords: Anabolic agents, Ergogenic, Doping, Iran, Body-building, Sports, Athlete

  5. 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

    2016-02-01

    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.

  6. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    Science.gov (United States)

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  7. New steroidal 17β-carboxy derivatives present anti-5α-reductase activity and anti-proliferative effects in a human androgen-responsive prostate cancer cell line.

    Science.gov (United States)

    Amaral, Cristina; Varela, Carla; Correia-da-Silva, Georgina; Tavares da Silva, Elisiário; Carvalho, Rui A; Costa, Saul C P; Cunha, Sara C; Fernandes, José O; Teixeira, Natércia; Roleira, Fernanda M F

    2013-11-01

    The androgens testosterone (T) and dihydrotestosterone (DHT), besides playing an important role in prostate development and growth, are also responsible for the development and progression of benign prostate hyperplasia (BPH) and prostate cancer. Therefore, the actions of these hormones can be antagonized by preventing the irreversible conversion of T into DHT by inhibiting 5α-reductase (5α-R). This has been a useful therapeutic approach for the referred diseases and can be achieved by using 5α-reductase inhibitors (RIs). Steroidal RIs, finasteride and dutasteride, are used in clinic for BPH treatment and were also proposed for chemoprevention of prostate cancer. Nevertheless, due to the increase in bone and muscle loss, impotency and occurrence of high-grade prostate tumours, it is important to seek for other potent and specific molecules with lower side effects. In the present work, we designed and synthesized steroids with the 3-keto-Δ(4) moiety in the A-ring, as in the 5α-R substrate T, and with carboxamide, carboxyester or carboxylic acid functions at the C-17β position. The inhibitory 5α-R activity, in human prostate microsomes, as well as the anti-proliferative effects of the most potent compounds, in a human androgen-responsive prostate cancer cell line (LNCaP cells), were investigated. Our results showed that steroids 3, 4 and 5 are good RIs, which suggest that C-17β lipophylic amides favour 5α-R inhibition. Moreover, these steroids induce a decrease in cell viability of stimulated LNCaP cells, in a 5α-R dependent-manner, similarly to finasteride. PMID:23933094

  8. 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.

  9. Wnt inhibitory factor 1 (Wif1) is regulated by androgens and enhances androgen-dependent prostate development.

    Science.gov (United States)

    Keil, Kimberly P; Mehta, Vatsal; Branam, Amanda M; Abler, Lisa L; Buresh-Stiemke, Rita A; Joshi, Pinak S; Schmitz, Christopher T; Marker, Paul C; Vezina, Chad M

    2012-12-01

    Fetal prostate development from urogenital sinus (UGS) epithelium requires androgen receptor (AR) activation in UGS mesenchyme (UGM). Despite growing awareness of sexually dimorphic gene expression in the UGS, we are still limited in our knowledge of androgen-responsive genes in UGM that initiate prostate ductal development. We found that WNT inhibitory factor 1 (Wif1) mRNA is more abundant in male vs. female mouse UGM in which its expression temporally and spatially overlaps androgen-responsive steroid 5α-reductase 2 (Srd5a2). Wif1 mRNA is also present in prostatic buds during their elongation and branching morphogenesis. Androgens are necessary and sufficient for Wif1 expression in mouse UGS explant mesenchyme, and testicular androgens remain necessary for normal Wif1 expression in adult mouse prostate stroma. WIF1 contributes functionally to prostatic bud formation. In the presence of androgens, exogenous WIF1 protein increases prostatic bud number and UGS basal epithelial cell proliferation without noticeably altering the pattern of WNT/β-catenin-responsive Axin2 or lymphoid enhancer binding factor 1 (Lef1) mRNA. Wif1 mutant male UGSs exhibit increased (Sfrp)2 and (Sfrp)3 expression and form the same number of prostatic buds as the wild-type control males. Collectively our results reveal Wif1 as one of the few known androgen-responsive genes in the fetal mouse UGM and support the hypothesis that androgen-dependent Wif1 expression is linked to the mechanism of androgen-induced prostatic bud formation.

  10. Ligand-induced conformational alterations of the androgen receptor analyzed by limited trypsinization: Studies on the mechanism of antiandrogen action

    NARCIS (Netherlands)

    C.W. Kuil (Cor); C.A. Berrevoets (Cor); E. Mulder (Eppo)

    1995-01-01

    textabstractLimited proteolysis of in vitro produced human androgen receptor was used to probe the different conformations of the receptor after binding of androgens and several antiandrogens. The results provide evidence for five different conformations of the receptor, as detected by the formation

  11. Fasting Blood Glucose and Lipid Profile Alterations following Twelve-Month Androgen Deprivation Therapy in Men with Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Hasan S. Sağlam

    2012-01-01

    Full Text Available Purpose. In this retrospective study, we aimed to investigate the effects of androgen deprivation therapy (ADT on blood glucose and blood cholesterol levels over a 12-month period. Materials and Methods. Between January 2010 and June 2012, the data of 44 patients with prostate cancer who were receiving ADT were collected from a hospital database. Patients with additional malignancy or diabetes and those who had been prescribed and were currently taking cholesterol-lowering medication were excluded from the study. Data (including fasting blood glucose levels and a cholesterol profile were collected and analysed statistically. A value <0.05 was considered statistically significant. Results. Twelve months after the initiation of ADT, fasting blood glucose (FBG, total cholesterol (TC, low-density lipoprotein (LDL cholesterol, high-density lipoprotein (HDL cholesterol, and triglyceride (TG levels changed. FBG, TC, LDL cholesterol, and TG increased significantly (, 0.000, 0.000, and 0.000, resp., while HDL cholesterol decreased (. Conclusion. ADT may increase FBG, TC, LDL cholesterol, and TG but decrease HDL cholesterol by the end of a year of treatment. Therefore, close followup may be needed as a consequence of one-year ADT regarding metabolic alterations.

  12. Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid hormones and the expression of the androgen receptor in the pituitary and adrenal glands of male turkeys (Meleagris gallopavo) during growth and development.

    Science.gov (United States)

    Kiezun, J; Kaminska, B; Jankowski, J; Dusza, L

    2015-01-01

    Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity.

  13. Identification and Characterization of the Androgen Receptor From the American Alligator, Alligator mississippiensis.

    Science.gov (United States)

    Miyagawa, Shinichi; Yatsu, Ryohei; Kohno, Satomi; Doheny, Brenna M; Ogino, Yukiko; Ishibashi, Hiroshi; Katsu, Yoshinao; Ohta, Yasuhiko; Guillette, Louis J; Iguchi, Taisen

    2015-08-01

    Androgens are essential for the development, reproduction, and health throughout the life span of vertebrates, particularly during the initiation and maintenance of male sexual characteristics. Androgen signaling is mediated by the androgen receptor (AR), a member of the steroid nuclear receptor superfamily. Mounting evidence suggests that environmental factors, such as exogenous hormones or contaminants that mimic hormones, can disrupt endocrine signaling and function. The American alligator (Alligator mississippiensis), a unique model for ecological research in that it exhibits environment-dependent sex determination, is oviparous and long lived. Alligators from a contaminated environment exhibit low reproductive success and morphological disorders of the testis and phallus in neonates and juveniles, both associated with androgen signaling; thus, the alterations are hypothesized to be related to disrupted androgen signaling. However, this line of research has been limited because of a lack of information on the alligator AR gene. Here, we isolated A mississippiensis AR homologs (AmAR) and evaluated receptor-hormone/chemical interactions using a transactivation assay. We showed that AmAR responded to all natural androgens and their effects were inhibited by cotreatment with antiandrogens, such as flutamide, p,p'-dichlorodiphenyldichloroethylene, and vinclozolin. Intriguingly, we found a spliced form of the AR from alligator cDNA, which lacks seven amino acids within the ligand-binding domain that shows no response to androgens. Finally, we have initial data on a possible dominant-negative function of the spliced form of the AR against androgen-induced AmAR. PMID:25974402

  14. Alteration of the hypothalamic-pituitary-gonadal axis in estrogen- and androgen-treated adult male leopard frog, Rana pipiens

    Directory of Open Access Journals (Sweden)

    Jones Jeremy T

    2005-01-01

    Full Text Available Abstract Background Gonadal steroids, in particular 5 alpha-dihydrotestosterone (DHT and 17 beta-estradiol (E2, have been shown to feed back on the hypothalamic-pituitary-gonadal (HPG axis of the ranid frog. However, questions still remain on how DHT and E2 impact two of the less-studied components of the ranid HPG axis, the hypothalamus and the gonad, and if the feedback effects are consistently negative. Thus, the goal of the study was to examine the effects of DHT and E2 upon the HPG axis of the gonadally-intact, sexually mature male leopard frogs, Rana pipiens. Methods R. pipiens were implanted with silastic capsules containing either cholesterol (Ch, a control, DHT, or E2 for 10 or 30 days. At each time point, steroid-induced changes in hypothalamic GnRH and pituitary LH concentrations, circulating luteinizing hormone (LH, and testicular histology were examined. Results Frogs implanted with DHT or E2 for 10 days did not show significant alterations in the HPG axis. In contrast, frogs implanted with hormones for 30 days had significantly lower circulating LH (for both DHT and E2, decreased pituitary LH concentration (for E2 only, and disrupted spermatogenesis (for both DHT and E2. The disruption of spermatogenesis was qualitatively similar between DHT and E2, although the effects of E2 were consistently more potent. In both DHT and E2-treated animals, a marked loss of all pre-meiotic germ cells was observed, although the loss of secondary spermatogonia appeared to be the primary cause of disrupted spermatogenesis. Unexpectedly, the presence of post-meiotic germ cells was either unaffected or enhanced by DHT or E2 treatment. Conclusions Overall, these results showed that both DHT and E2 inhibited circulating LH and disrupted spermatogenesis progressively in a time-dependent manner, with the longer duration of treatment producing the more pronounced effects. Further, the feedback effects exerted by both steroid hormones upon the HPG axis were

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

    OpenAIRE

    Heather, Alison K.; Cooper, Elliot R.; McGrath, Kristine C. Y.

    2013-01-01

    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 sup...

  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 uri

  17. A competitive inhibitor that reduces recruitment of androgen receptor to androgen-responsive genes.

    Science.gov (United States)

    Cherian, Milu T; Wilson, Elizabeth M; Shapiro, David J

    2012-07-01

    The androgen receptor (AR) has a critical role in the growth and progression of androgen-dependent and castration-resistant prostate cancers. To identify novel inhibitors of AR transactivation that block growth of prostate cancer cells, a luciferase-based high-throughput screen of ~160,000 small molecules was performed in cells stably expressing AR and a prostate-specific antigen (PSA)-luciferase reporter. CPIC (1-(3-(2-chlorophenoxy) propyl)-1H-indole-3-carbonitrile) was identified as a small molecule that blocks AR transactivation to a greater extent than other steroid receptors. CPIC inhibited AR-mediated proliferation of androgen-sensitive prostate cancer cell lines, with minimal toxicity in AR-negative cell lines. CPIC treatment also reduced the anchorage-independent growth of LAPC-4 prostate cancer cells. CPIC functioned as a pure antagonist by inhibiting the expression of AR-regulated genes in LAPC-4 cells that express wild-type AR and exhibited weak agonist activity in LNCaP cells that express the mutant AR-T877A. CPIC treatment did not reduce AR levels or alter its nuclear localization. We used chromatin immunoprecipitation to identify the site of action of CPIC. CPIC inhibited recruitment of androgen-bound AR to the PSA promoter and enhancer sites to a greater extent than bicalutamide. CPIC is a new therapeutic inhibitor that targets AR-mediated gene activation with potential to arrest the growth of prostate cancer.

  18. 合成类固醇激素的检测技术研究进展与思考%Progress and Consideration on Detection Technique of Anabolic Androgenic Steroid

    Institute of Scientific and Technical Information of China (English)

    沙继斌

    2010-01-01

    综述了近年来国际与国内对合成类固醇激素(anabolic androgenic steroid,AAS)检测技术的研究进展,分析了目前应用的检测技术中可能存在的疑问与不足.在了解了合成类固醇激素在体内作用的基本特点的基础上,建议尝试应用目前所具备的蛋白质组的技术手段来进行合成类固醇激素的体内检测,初步确认了利用该项技术手段发觉分子标记物的可行性,可以作为目前化学分析手段的有益补充.

  19. Expression of the androgen receptor in the testes and the concentrations of gonadotropins and sex steroid hormones in male turkeys (Meleagris gallopavo) during growth and development.

    Science.gov (United States)

    Kiezun, J; Leska, A; Kaminska, B; Jankowski, J; Dusza, L

    2015-04-01

    Androgens, including testosterone (T) and androstenedione (A4), are essential for puberty, fertility and sexual functions. The biological activity of those hormones is mediated via the androgen receptor (AR). The regulation of androgen action in birds is poorly understood. Therefore, the present study analysed mRNA and protein expression of AR in the testes, plasma concentrations of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), T, A4 and oestradiol (E2), as well as the levels of T, A4 and E2 in testicular homogenates of male turkeys (Meleagris gallopavo) at the age of 4, 8, 12, 16, 20, 24 and 28weeks. Plasma concentrations of LH and FSH, as well as plasma and testicular levels of T and A4 began to increase at 20weeks of age. The lowest plasma levels of E2 were noted at 20weeks relative to other growth stages. The 20th week of life seems to be the key phase in the development of the reproductive system of turkeys. The AR protein was found in the nuclei of testicular cells in all examined growth stages. Higher expression of AR protein in the testes beginning at 20weeks of age was accompanied by high plasma concentrations of LH and high plasma and testicular levels of androgens. This relationship seems to be necessary to regulate male sexual function.

  20. Inhaled Steroids

    Science.gov (United States)

    ... Medications > Long-Term Control Medications > Inhaled Steroids Inhaled Steroids What are some common inhaled steroids? How are ... more about steroids? What are some common inhaled steroids? Common inhaled steroids include: Asmanex ® (mometasone) Alvesco ® (ciclesonide) ...

  1. The novel non-steroidal selective androgen receptor modulator S-101479 has additive effects with bisphosphonate, selective estrogen receptor modulator, and parathyroid hormone on the bones of osteoporotic female rats.

    Science.gov (United States)

    Furuya, Kazuyuki; Yamamoto, Noriko; Ohyabu, Yuki; Makino, Akito; Morikyu, Teruyuki; Ishige, Hirohide; Kuzutani, Kazuya; Endo, Yasuhisa

    2012-01-01

    We have studied non-steroidal selective androgen receptor modulators (SARMs) to develop anti-osteoporosis drugs for males and females. Many SARMs have been studied for their anabolic effects on bone or muscle with reduced virilizing effects in male animals. However, the tissue selectivities of these agents in female animals have not been fully evaluated. We evaluated the novel SARM S-101479 from tetrahydroquinoline libraries in ovariectomized (OVX) rats. S-101479 preferentially bound to the androgen receptor with nanomolar affinity among nuclear receptors. It increased the bone mineral density (BMD) of femurs and diminished the effects on the uterus and clitoral gland in OVX rats. We then compared the effect of S-101479 on bone with those of commercial anti-osteoporosis drugs such as alendronate, raloxifene, and teriparatide. Furthermore, we evaluated the effects of combination treatments with these agents in OVX rats. After 16-week treatment, all agents significantly increased BMD, but the magnitude of bone mineral content (BMC) and/or bone size (projected bone area) were different. Alendronate, raloxifene, and teriparatide maintained BMC and bone size in this experimental dose. Only S-101479 increased BMC with bone size on single treatments. In combination treatment, S-101479 significantly increased BMC and bone size compared with single treatments of other agents. S-101479, like natural androgen, may have showed periosteal bone formation of the cortical area and indicated additive effects with commercial anti-osteoporosis drugs. These results indicate that S-101479 may be a useful anti-osteoporosis drug, particularly for patients with established severe osteoporosis.

  2. Adolescents and Steroids: A User Perspective.

    Science.gov (United States)

    Office of Inspector General (DHHS), Washington, DC.

    Anabolic-androgenic steroids ("steroids") are synthetic derivatives of the natural male hormone testosterone. They were first used non-medically by elite athletes seeking to improve performance. More recently, however, steroid use has filtered down to high school and junior high school levels. The purpose of this study was to describe adolescent…

  3. Altered diurnal pattern of steroid hormones in relation to various behaviors, external factors and pathologies: A review.

    Science.gov (United States)

    Collomp, K; Baillot, A; Forget, H; Coquerel, A; Rieth, N; Vibarel-Rebot, N

    2016-10-01

    The adrenal and gonadal stress steroids [i.e., cortisol, testosterone and dehydroepiandrosterone (DHEA)] have gathered considerable attention in the last few decades due to their very broad physiological and psychological actions. Their diurnal patterns have become a particular focus following new data implicating altered diurnal hormone patterns in various endocrine, behavioral and cardiovascular risk profiles. In this review of the current literature, we present a brief overview of the altered diurnal patterns of these hormones that may occur in relation to chronic stress, nutritional behaviors, physical exercise, drugs and sleep deprivation/shift. We also present data on the altered diurnal hormone patterns implicated in cardiometabolic and psychiatric/neurologic diseases, cancer and other complex pathologies. We consider the occasionally discrepant results of the studies, and summarize the current knowledge in this new field of interest, underlining the potential effects on both biological and psychological functioning, and assess the implications of these effects. Last, we conclude with some practical considerations and perspectives. PMID:27235338

  4. Esterification of vertebrate like steroids in molluscs: a target of endocrine disruptors?

    Science.gov (United States)

    Giusti, Arnaud; Joaquim-Justo, Célia

    2013-11-01

    Alterations of the reproductive organs of gastropod molluscs exposed to pollutants have been reported in natural populations for more than 40 years. In some cases, these impacts have been linked to exposure to endocrine-disrupting chemicals (EDCs), which are known to induce adverse impacts on vertebrates, mainly by direct binding to steroid receptors or by altering hormone synthesis. Investigations on the mechanisms of action of endocrine disruptors in molluscs show that EDCs induce modifications of endogenous titres of androgens (e.g., testosterone, androstenedione) and oestrogens (e.g., 17ß-oestradiol). Alterations of the activity of enzymes related to steroid metabolism (i.e., cytochrome P-450 aromatase, acyltransferases) are also often observed. In bivalves and gastropods, fatty acid esterification of steroids might constitute the major regulation of androgen and oestrogen homeostasis. The present review indicates that metabolism of steroid hormones to fatty acid esters might be a target of synthetic EDCs. Alterations of this process would impact the concentrations of free, potentially bioactive, form of steroids. PMID:24004916

  5. Molecular mechanisms of androgen and antiandrogen action

    NARCIS (Netherlands)

    C.W. Kuil (Cor)

    1997-01-01

    textabstractThe steroid hormones testosterone and 5a-dihydrotestosterone (androgens) control the development, differentiation and function of male reproductive and accessory sex tissues, such as seminal vesicle, epididymis and prostate. Changes in cell properties induced by androgens require the pre

  6. 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

  7. Synthetic Androgens as Designer Supplements

    OpenAIRE

    Joseph, Jan Felix; Parr, Maria Kristina

    2015-01-01

    Anabolic androgenic steroids (AAS) are some of the most common performance enhancing drugs (PED) among society. Despite the broad spectrum of adverse effects and legal consequences, AAS are illicitly marketed and distributed in many countries. To circumvent existing laws, the chemical structure of AAS is modified and these designer steroids are sold as nutritional supplements mainly over the Internet. Several side effects are linked with AAS abuse. Only little is known about the pharmacologic...

  8. External calibration in gas chromatography-combustion-isotope ratio mass spectrometry measurements of endogenous androgenic anabolic steroids in sports doping control.

    Science.gov (United States)

    Kioussi, Maroula K; Angelis, Yiannis S; Cawley, Adam T; Koupparis, Michalis; Kazlauskas, Rymantas; Brenna, J Thomas; Georgakopoulos, Costas G

    2011-08-19

    An alternative calibration procedure for the gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) measurements of the World Antidoping Agency (WADA) Accredited Laboratories is presented. To alleviate the need for externally calibrated CO₂ gas for GC-C-IRMS analysis of urinary steroid metabolites, calibration using an external standard mixture solution of steroids with certified isotopic composition was investigated. The reference steroids of the calibration mixture and routine samples underwent identical instrumental processes. The calibration standards bracketed the entire range of the relevant δ¹³C values for the endogenous and exogenous steroids as well as their chromatographic retention times. The certified δ¹³C values of the reference calibrators were plotted in relation to measured m/z ¹³CO₂/¹²CO₂ (i.e. R(45/44)) mass spectrometric signals of each calibrator. δ¹³C values of the sample steroids were calculated from the least squares fit through the calibration curve. The effect of the external calibration on δ¹³C values, using the same calibration standards and set of urine samples but different brands of GC-C-IRMS instruments, was assessed by an interlaboratory study in the WADA Accredited Laboratories of Sydney, Australia and Athens, Greece. Relative correspondence between the laboratories for determination of androsterone, etiocholanolone, 5β-androstane-3α,17β-diacetate, and pregnanediacetate means were SD(δ¹³C)=0.12‰, 0.58‰, -0.34‰, and -0.40‰, respectively. These data demonstrate that accurate intralaboratory external calibration with certified steroids provided by United States Antidoping Agency (USADA) and without external CO₂ calibration is feasible and directly applicable to the WADA Accredited Laboratories for the harmonization of the GC-C-IRMS measurements.

  9. 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.

  10. Stress and Androgen Activity During Fetal Development.

    Science.gov (United States)

    Barrett, Emily S; Swan, Shanna H

    2015-10-01

    Prenatal stress is known to alter hypothalamic-pituitary-adrenal axis activity, and more recent evidence suggests that it may also affect androgen activity. In animal models, prenatal stress disrupts the normal surge of testosterone in the developing male, whereas in females, associations differ by species. In humans, studies show that (1) associations between prenatal stress and child outcomes are often sex-dependent, (2) prenatal stress predicts several disorders with notable sex differences in prevalence, and (3) prenatal exposure to stressful life events may be associated with masculinized reproductive tract development and play behavior in girls. In this minireview, we examine the existing literature on prenatal stress and androgenic activity and present new, preliminary data indicating that prenatal stress may also modify associations between prenatal exposure to diethylhexyl phthalate, (a synthetic, antiandrogenic chemical) and reproductive development in infant boys. Taken together, these data support the hypothesis that prenatal exposure to both chemical and nonchemical stressors may alter sex steroid pathways in the maternal-placental-fetal unit and ultimately alter hormone-dependent developmental endpoints. PMID:26241065

  11. Postmenopausal serum androgens, oestrogens and breast cancer risk : the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Kaaks, R; Rinaldi, S; Key, TJ; Berrino, F; Peeters, PHM; Biessy, C; Dossus, L; Lukanova, A; Binghan, S; Khaw, KTG; Allen, NE; Bueno-De-Mesquita, HB; van Gils, CH; Grobbee, D; Boeing, H; Lahmann, PH; Nagel, G; Chang-Claude, J; Clavel-Chapelon, F; Fournier, A; Thiebaut, A; Gonzalez, CA; Quiros, [No Value; Tormo, MJ; Ardanaz, E; Amiano, P; Krogh, [No Value; Palli, D; Panico, S; Tumino, R; Vineis, P; Trichopoulou, A; Kalapothaki, [No Value; Trichopoulos, D; Ferrari, P; Norat, T; Saracci, R; Riboli, E

    2005-01-01

    Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids - notably androgens and oestrogens - promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has

  12. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition

    NARCIS (Netherlands)

    Kaaks, R.; Rinaldi, S.; Key, T.J.; Berrino, F.; Peeters, P.H.M.; Biessy, C.; Dossus, L.; Lukanova, A.; Bingham, S.; Khaw, K-T.; Allen, N.E.; Bueno-de-Mesquita, H.B.; Gils, C.H. van; Grobbee, D.E.; Boeing, H.; Lahmann, P.H.; Nagel, G.; Chang-Claude, J.; Clavel-Chapelon, F.; Fournier, A.; Thiébaut, A.; Gonzalez, C.A.; Quirós, J.R.; Tormo, M-J.; Ardanaz, E.; Amiano, P.; Krogh, V.; Palli, D.; Panico, S.; Tumino, R.; Vineis, P.; Trichopoulou, A.; Kalapothaki, V.; Trichopoulos, D.; Ferrari, P.; Norat, T.; Saracci, R.; Riboli, E.

    2005-01-01

    Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has

  13. Alterations in the steroid hormone receptor co-chaperone FKBPL are associated with male infertility: a case-control study

    LENUS (Irish Health Repository)

    Sunnotel, Olaf

    2010-03-08

    Abstract Background Male infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding protein family, can result in male infertility. In the case of FKBP52, this reflects an important role in potentiating Androgen Receptor (AR) signalling in the prostate and accessory glands, but not the testis. In infertile men, no mutations of FKBP52 or FKBP6 have been found so far, but the gene for FKBP-like (FKBPL) maps to chromosome 6p21.3, an area linked to azoospermia in a group of Japanese patients. Methods To determine whether mutations in FKBPL could contribute to the azoospermic phenotype, we examined expression in mouse and human tissues by RNA array blot, RT-PCR and immunohistochemistry and sequenced the complete gene from two azoospermic patient cohorts and matching control groups. FKBPL-AR interaction was assayed using reporter constructs in vitro. Results FKBPL is strongly expressed in mouse testis, with expression upregulated at puberty. The protein is expressed in human testis in a pattern similar to FKBP52 and also enhanced AR transcriptional activity in reporter assays. We examined sixty patients from the Japanese patient group and found one inactivating mutation and one coding change, as well as a number of non-coding changes, all absent in fifty-six controls. A second, Irish patient cohort of thirty showed another two coding changes not present in thirty proven fertile controls. Conclusions Our results describe the first alterations in the gene for FKBPL in azoospermic patients and indicate a potential role in AR-mediated signalling in the testis.

  14. Environmental concentrations of anti-androgenic pharmaceuticals do not impact sexual disruption in fish alone or in combination with steroid oestrogens

    OpenAIRE

    Green, Christopher; Brian, Jayne; Kanda, Rakesh; Scholze, Martin; Williams, Richard; Jobling, Susan

    2015-01-01

    This article has been made available through the Brunel Open Access Publishing Fund. Sexual disruption in wild fish has been linked to the contamination of river systems with steroid oestrogens, including the pharmaceutical 17α-ethinylestradiol, originating from domestic wastewaters. As analytical chemistry has advanced, more compounds derived from the human usage of pharmaceuticals have been identified in the environment and questions have arisen as to whether these additional pharmaceuti...

  15. 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. PMID:26094581

  16. Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess

    Science.gov (United States)

    To date, animal models with naturally occurring androgen excess have not been identified. Serendipitously, we discovered two subpopulations of cows with dramatically different follicular fluid androgen concentrations in dominant follicles within our research herd. In the cow, androstenedione is the...

  17. 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

    2016-01-01

    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. PMID:27265420

  18. 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.

    2016-01-01

    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. PMID:27265420

  19. [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. PMID:23483467

  20. 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.

  1. 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. PMID:26980272

  2. Mono-hydroxy methoxychlor alters levels of key sex steroids and steroidogenic enzymes in cultured mouse antral follicles.

    Science.gov (United States)

    Craig, Zelieann R; Leslie, Traci C; Hatfield, Kimberly P; Gupta, Rupesh K; Flaws, Jodi A

    2010-12-01

    Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by decreasing antral follicle numbers and increasing follicular death. MXC is metabolized in the body to mono-hydroxy MXC (mono-OH). Little is known about the effects of mono-OH on the ovary. Thus, this work tested the hypothesis that mono-OH exposure decreases production of 17β-estradiol (E₂) by cultured mouse antral follicles. Antral follicles were isolated from CD-1 mice (age 35-39 days) and exposed to dimethylsulfoxide (DMSO), or mono-OH (0.1-10 μg/mL) for 96 h. Media and follicles were collected for analysis of sex steroid levels and mRNA expression, respectively. Mono-OH treatment (10 μg/mL) decreased E(2) (DMSO: 3009.72±744.99 ng/mL; mono-OH 0.1 μg/mL: 1679.66±461.99 ng/mL; 1 μg/mL: 1752.72±532.41 ng/mL; 10 μg/mL: 45.89±33.83 ng/mL), testosterone (DMSO: 15.43±2.86 ng/mL; mono-OH 0.1μg/mL: 17.17±4.71 ng/mL; 1 μg/mL: 13.64±3.53 ng/mL; 10 μg/mL: 1.29±0.23 ng/mL), androstenedione (DMSO: 1.92±0.34 ng/mL; mono-OH 0.1 μg/mL: 1.49±0.43ng/mL; 1 μg/mL: 0.64±0.31 ng/mL; 10 μg/mL: 0.12±0.06 ng/mL) and progesterone (DMSO: 24.11±4.21 ng/mL; mono-OH 0.1μg/mL: 26.77±4.41 ng/mL; 1 μg/mL: 20.90±3.75 ng/mL; 10 μg/mL: 9.44±2.97 ng/mL) levels. Mono-OH did not alter expression of Star, Hsd3b1, Hsd17b1 and Cyp1b1, but it did reduce levels of Cyp11a1, Cyp17a1 and Cyp19a1 mRNA. Collectively, these data suggest that mono-OH significantly decreases levels of key sex steroid hormones and the expression of enzymes required for steroidogenesis.

  3. Short-term exposure to low concentrations of the synthetic androgen methyltestosterone affects vitellogenin and steroid levels in adult male zebrafish (Danio rerio).

    Science.gov (United States)

    Andersen, Lene; Goto-Kazeto, Rie; Trant, John M; Nash, Jon P; Korsgaard, Bodil; Bjerregaard, Poul

    2006-03-10

    Short-term effects of methyltestosterone (MT) on the endocrine system of adult male zebrafish (Danio rerio) were examined. Males were exposed to 0, 4.5, 6.6, 8.5, 19.8, 35.9, 62.3 ng MT/l and ethinylestradiol (EE2) (26.4 ng/l) for 7 days. Several physiological endpoints that may be affected by endocrine disrupters were analysed, specifically vitellogenin (VTG) concentration, estradiol (E2), testosterone (T), and 11-ketotestosterone (KT) content, brain aromatase activity and gene expression of CYP19A1 and CYP19A2 in the testis. Exposure to the lowest MT concentration (4.5 ng MT/l), and the EE2 increased the concentration of VTG significantly compared to solvent control group. Exposure to higher concentrations of MT did not increase VTG levels. Endogenous KT and T levels decreased significantly in a concentration-dependent manner in response to the MT exposure and the lowest effective concentrations were 6.4 and 8.5 ng MT/l, respectively. The levels of KT and T were also significantly suppressed by EE2 when compared to the solvent control group. Significant decreases in endogenous E2 levels were found in some MT groups but it was not possible to distinguish a simple concentration-response relationship. No effects of MT or EE2 on the brain aromatase activity or on testicular gene expression of CYP19A1 and CYP19A2 were detected. The results show that androgens such as MT can act as endocrine disrupters even at very low concentrations.

  4. Androgen receptor: structure, role in prostate cancer and drug discovery

    OpenAIRE

    Tan, MH Eileen; Li, Jun; Xu, H. Eric; Melcher, Karsten; Yong, Eu-Leong

    2014-01-01

    Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer ...

  5. Naturally occurring steroids in Xenopus oocyte during meiotic maturation. Unexpected presence and role of steroid sulfates.

    Science.gov (United States)

    Haccard, Olivier; Dupré, Aude; Liere, Philippe; Pianos, Antoine; Eychenne, Bernard; Jessus, Catherine; Ozon, René

    2012-10-15

    In the ovary, oocytes are surrounded by follicle cells and arrested in prophase of meiosis I. Although steroidogenic activity of follicle cells is involved in oogenesis regulation, clear qualitative and quantitative data about the steroid content of follicles are missing. We measured steroid levels of Xenopus oocytes and follicles by gas chromatography-mass spectrometry. We show that dehydroepiandrosterone sulfate is the main steroid present in oocytes. Lower levels of free steroids are also detected, e.g., androgens, whereas progesterone is almost undetectable. We propose that sulfatation is a protective mechanism against local variations of active steroids that could be deleterious for follicle-enclosed oocytes. Steroid levels were measured after LH stimulation, responsible for the release by follicle cells of a steroid signal triggering oocyte meiosis resumption. Oocyte levels of androgens rise slowly during meiosis re-entry whereas progesterone increases abruptly to micromolar concentration, therefore representing the main physiological mediator of meiosis resumption in Xenopus oocyte. PMID:22687883

  6. 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.

  7. 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.

  8. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients

    OpenAIRE

    Lallous, Nada; Volik, Stanislav V.; Awrey, Shannon; LeBlanc, Eric; Tse, Ronnie; Murillo, Josef; Singh, Kriti; Azad, Arun A.; Wyatt, Alexander W.; LeBihan, Stephane; Chi, Kim N.; Gleave, Martin E.; Paul S. Rennie; Collins, Colin C; Cherkasov, Artem

    2016-01-01

    Background The androgen receptor (AR) is a pivotal drug target for the treatment of prostate cancer, including its lethal castration-resistant (CRPC) form. All current non-steroidal AR antagonists, such as hydroxyflutamide, bicalutamide, and enzalutamide, target the androgen binding site of the receptor, competing with endogenous androgenic steroids. Several AR mutations in this binding site have been associated with poor prognosis and resistance to conventional prostate cancer drugs. In orde...

  9. Steroid profiling in doping analysis

    NARCIS (Netherlands)

    Kerkhof, Daniël Henri van de

    2002-01-01

    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 p

  10. 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...

  11. 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.

  12. 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.

  13. Steroid profiling and confirmation of the T/E - ratio in doping control

    OpenAIRE

    Hanssen, Kine Østnes

    2010-01-01

    Anabolic-androgenic steroids are naturally occurring or synthetic derivates of male sex hormones. All anabolic-androgenic steroids are prohibited by the World Anti-Doping Agency because of their muscle growth stimulating effect. At the Seibersdorf Doping-Control Laboratory, urine samples from athletes are first screened with a screen testing procedure to obtain an endogenous steroid profile, in order to identify samples suspected of containing endogenous steroids of exogenous origin. Thi...

  14. Oral Steroids (Steroid Pills and Syrups)

    Science.gov (United States)

    ... Disease Medications > Quick-Relief Medications > Oral Steroids Oral Steroids (Steroid Pills and Syrups) How are steroid pills and ... Want to learn more about steroids? How are steroid pills and syrups used? Steroid pills and syrups ...

  15. Selective androgen receptor modulators for frailty and osteoporosis.

    Science.gov (United States)

    Kilbourne, Edward J; Moore, William J; Freedman, Leonard P; Nagpal, Sunil

    2007-10-01

    Androgens play an important role not only in male sexual differentiation, puberty, sexual behavior and spermatogenesis, but also in the maintenance of bone architecture and muscle mass and strength. For decades, steroidal androgens have been used by hypogonadal and aging men as hormone replacement therapy, and abused by prominent athletes as anabolic agents for enhancing physical performance. The use of steroidal androgens is associated with hepatotoxicity, potential for prostate stimulation, virilizing actions and other side effects resulting from their cross-reactivity to related steroid receptors. Therefore, to utilize the therapeutic potential of the androgen receptor for the treatment of indications such as osteoporosis and frailty, several pharmaceutical and biotechnology companies are developing non-steroidal tissue-selective androgen receptor modulators (SARMs) that retain the beneficial properties of natural androgens and exhibit better therapeutic indices. This article reviews the mechanism of androgen action, novel non-steroidal ligands under development and future directions of SARM research for the discovery of novel modulators for frailty and osteoporosis.

  16. Androgen and bone mass in men

    Institute of Scientific and Technical Information of China (English)

    AnnieW.C.Kung

    2003-01-01

    Androgens have multiple actions on the skeleton throughout life. Androgens promote skeletal growth and accumulation of minerals during puberty and adolescence and stimulate osteoblast but suppress osteoclast function,activity and lifespan through complex mechanisms. Also androgens increase periosteal bone apposition, resulting in larger bone size and thicker cortical bone in men. There is convincing evidence to show that aromatization to estrogens was an important pathway for mediating the action of testosterone on bone physiology. Estrogen is probably the dominant sex steroid regulating bone resorption in men, but both testosterone and estrogen are important in maintaining bone formation. ( Asian J Androl 2003 Jun; 5: 148-154)

  17. Social modulation of androgen levels in male teleost fish

    OpenAIRE

    Oliveira, R. F.; Hirschenhauser, K.; Carneiro, L. A.; Canario, Adelino V. M.

    2002-01-01

    Androgens are classically thought of as the sex steroids controlling male reproduction. However, in recent years evidence has accumulated showing that androgens can also be affected by the interactions between conspecifics, suggesting reciprocal interactions between androgens and behaviour. These results have been interpreted as an adaptation for individuals to adjust their agonistic motivation and to cope with changes in their social environment. Thus, male–male interactions would stimulate ...

  18. 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...

  19. Anabolic Steroids

    Science.gov (United States)

    Anabolic steroids are man-made substances related to male sex hormones. Doctors use anabolic steroids to treat some hormone problems in men, ... from some diseases. Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. ...

  20. Alterations in luteal production of androstenedione, testosterone, and estrone, but not estradiol, during mid- and late pregnancy in pigs: effects of androgen deficiency.

    Science.gov (United States)

    Grzesiak, Malgorzata; Knapczyk-Stwora, Katarzyna; Ciereszko, Renata E; Wieciech, Iwona; Slomczynska, Maria

    2014-09-15

    Recently, we have found that flutamide-induced androgen deficiency altered progesterone production in the porcine corpus luteum (CL) during mid- and late pregnancy. Herein, we tested whether flutamide administration subsequently influences androgen and estrogen metabolism in the CL of pregnancy. Pregnant gilts were treated with flutamide between Days 43 and 49 (GD50F), 83 and 89 (GD90F), or 101 and 107 (GD108F) of gestation. Corpora lutea (CLs) were collected from treated and nontreated (control) pigs. The concentrations of androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) together with the levels of expression of mRNAs and proteins for cytochrome P450 17α-hydroxylase/c17-20 lyase (CYP17A1), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), cytochrome P450 aromatase (CYP19A1), and 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) were measured in the CL of control and flutamide-treated animals. Steroidogenic enzymes were also immunolocalized in luteal tissues. The luteal concentrations of A4 and T were higher in the GD50F (P = 0.006, P = 0.03) and GD108F (P = 0.005, P = 0.035) groups, but lower in the GD90F (P = 0.004, P = 0.014) group. The E1 level was greater only in the GD90F (P = 0.03) and GD108F (P = 0.035) groups, whereas E2 concentration was not affected by flutamide treatment. Increased luteal CYP17A1 mRNA and protein expression was found in the GD50F (P = 0.002, P = 0.03) and GD108F (P = 0.0026, P = 0.03) groups, but reduced in the GD90F (P = 0.002, P = 0.03) group. mRNA of 17β-HSD1 was upregulated in the GD50F (P = 0.0005) group, but downregulated in the GD90F (P = 0.002) and GD108F (P = 0.0005) groups. In contrast, 17β-HSD1 protein expression was higher in the GD50F and GD108F (P = 0.03) groups, but lower in the GD90F (P = 0.03) group. Both CYP19A1 mRNA and protein levels were greater in the GD90F (P = 0.001, P = 0.028) and GD108F (P = 0.005, P = 0.03) groups. Neither 17β-HSD7 mRNA nor protein level were affected by

  1. 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.

  2. Androgen receptor modulators: a marriage of chemistry and biology.

    Science.gov (United States)

    McEwan, Iain J

    2013-06-01

    Androgenic steroids are important for male development in utero and secondary sexual characteristics at puberty. In addition, androgens play a role in non-reproductive tissues, such as bone and muscle in both sexes. The actions of the androgens testosterone and dihydrotestosterone are mediated by a single receptor protein, the androgen receptor. Over the last 60-70 years there has been considerable research interest in the development of inhibitors of androgen receptor for the management of diseases such as prostate cancer. However, more recently, there is also a growing appreciation of the need for selective androgen modulators that would demonstrate tissue-selective agonist or antagonist activity. The chemistry and biology of selective agonists, antagonists and selective androgen receptor modulators will be discussed in this review.

  3. PET imaging of brain sex steroid hormone receptors and the role of estrogen in depression

    NARCIS (Netherlands)

    Khayum, Mohamed Abdul

    2015-01-01

    Androgens and estrogens are steroid hormones that are involved in several neurodegenerative and psychiatric disorders. Decreased levels of steroid hormones are associated with e.g. decreased cognition, anxiety and depression. Androgens and estrogens exert their biological effects through their corre

  4. Computational Investigation on the Allosteric Modulation of Androgen Receptor

    Institute of Scientific and Technical Information of China (English)

    OU Min-Rui; LI Jun-Qian

    2012-01-01

    Androgens have similar structures with different biological activities. To identify molecular determinants responsible for the activity difference, we have docked six steroidal androgens to the binding site or the surface of androgen receptor by using molecular docking with computational investigation. The energy was calculated respectively based on the QM (quantum mechanics) and MM (molecular mechanics) methods. The result shows that the allosteric modulation of androgen receptor plays an important role in the binding process between androgens and receptor. The open state receptor is less stable than the close state one, but the latter is more favorable for binding with androgens. It is worthy of note that when the androgen receptors binding or without binding with androgen are in close state, they are difficult to return to their open state. This phenomenon is an exception of the well known two-state model theory in which the two states are reversible. Whether the internal of close state androgen receptor has a combination of androgen or not, the androgen receptor surface can be combined with another androgen, and their surface binding energies could be very close. The result is consistent with the experimental observations, but this phenomenon of continuous combination from open state is also an exception of the two-state model theory.

  5. Steroid metabolism in the mouse placenta

    International Nuclear Information System (INIS)

    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 [3H]-dehydroepiandrosterone and [3H]-progesterone by mouse placental tissue in vitro is studied. The metabolism of [3H]-progesterone by the mouse fetal adrenal in vitro is also studied

  6. ANDROGEN LEVELS IN PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    M. Valadan

    2006-08-01

    Full Text Available Preeclampsia is a major cause of morbidity and mortality during pregnancy. Several independent investigators have demonstrated the association of androgens with hypertension. The main purpose of this study was to determine whether maternal levels of sex hormones, especially testosterone, are higher in patients with preeclampsia than in matched normotensive control subjects. Serum levels of testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S and estradiol were measured in 60 subjects in the 3rd trimester of pregnancy with documented preeclampsia (including 30 cases of mild and 30 cases of severe preeclampsia and 60 healthy normotensive women with similar maternal and gestational ages and body mass index (BMI and neonatal sex. All subjects were primigravid with singleton pregnancies. Cases of polycystic ovary (PCO, diabetes, chronic hypertension and chronic systemic diseases such as lupus and patients using steroid hormones and anti-hypertensive drugs were excluded. Levels of testosterone, DHEA-S and estradiol were not higher in primigravid women with preeclampsia than in normotensive women with similar gestational and maternal ages, BMI and neonatal sex. There were no significant differences in sex hormones measured between groups of mild and severe preeclampsia and normotensive women. There were also no significant differences in sex hormone levels according to neonatal sex. These findings are against the hypothesis of mediating or amplifying role of high androgen levels in pathophysiology of preeclampsia.

  7. Yolk androgens reduce offspring survival.

    Science.gov (United States)

    Sockman, K W; Schwabl, H

    2000-07-22

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those of first-laid eggs in which we injected vehicle as a control. Compared to controls, injection of T and A4 at a dose intended to increase their levels to those of later-laid eggs delayed hatching and reduced nestling growth and survival rates. Yolk androgen treatment of egg 1 had no effect on survival of siblings hatching from subsequently laid eggs. The adverse actions of yolk androgen treatment in the kestrel are in contrast to the favourable actions of yolk T treatment found previously in canaries (Serinus canaria). Additional studies are necessary in order to determine whether the deposition of yolk androgens is an adaptive form of parental favouritism or an adverse by-product of endocrine processes during egg formation. Despite its adaptive significance, such 'transgenerational' effects of steroid hormones may have helped to evolutionarily shape the hormonal mechanisms regulating reproduction. PMID:10983830

  8. Androgen receptor mutations

    OpenAIRE

    Brinkmann, Albert; Jenster, Guido; Ris-Stalpers, Carolyn; Korput, J. A G M; Brüggenwirth, Hennie; Boehmer, A.L.; Trapman, Jan

    1995-01-01

    textabstractMale 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. At least three pathological situations are associated with abnormal androgen receptor structure and function: androgen insensitivity syndrome (AIS), spinal and bulbar muscular atrophy (SBMA) and prostate cancer. In the X-linked androgen insensitivity syn...

  9. Study on two steroidal sex hormones in rice

    Institute of Scientific and Technical Information of China (English)

    TAOYoubuo

    1998-01-01

    Steroidal sex hormones including androgens and estrogens are important in the reproductive development of mammals. A number of studies suggested that these steroids might have similar functions in plants, A latest research on Nongken 58s, a photoperiod-sensitive genie male sterile rice (PGMR),

  10. 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.

  11. 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

  12. Neonatal androgenization exacerbates alcohol-induced liver injury in adult rats, an effect abrogated by estrogen.

    Directory of Open Access Journals (Sweden)

    Whitney M Ellefson

    Full Text Available Alcoholic liver disease (ALD affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2 and ethanol metabolizing enzymes (cytochrome P450, CYP450 are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl, androgenized females (Andro and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood.

  13. Development of selective androgen receptor modulators and their therapeutic applications.

    Science.gov (United States)

    Chen, Fang; Rodan, Gideon A; Schmidt, Azi

    2002-01-01

    Androgens control a broad range of physiological functions. The androgen receptor (AR), a steroid receptor that mediates the diverse biological actions of androgens, is a ligand inducible transcription factor. Abnormalities in the androgen signaling system result in many disturbances ranging from changes in gender determination and sexual development to psychiatric and emotional disorders. Androgen replacement therapy can improve many clinical conditions including hypogonadism and osteoporosis, but is limited by the lack of efficacious and safe therapeutic agents with easy delivery options. Recent progress in the area of gene regulation by steroid receptors and by selective receptor modulators provides an opportunity to examine if selective androgen receptor modulators (SARMs) could address some of the problems associated with current androgen therapy. Since the composition of the transcriptional initiation complex recruited by liganded AR determines the specificity of gene regulation, synthetic ligands aimed at initiating transcription of tissue and promoter specific genes offers hope for developing better androgen therapy. Establishment of assays that predict synthetic ligand activity is critical for SARM development. Advancement in high throughput compound screening and gene fingerprinting technologies, such as microarrays and proteomics, will facilitate and accelerate identification of effective SARMs.

  14. Aberrant splicing of androgenic receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Ris-Stalpers, C.; Kuiper, G.G.J.M.; Faber, P.W.; van Rooij, H.C.J.; Degenhart, H.J.; Trapman, J.; Brinkmann, A.O. (Erasmus Univ., Rotterdam (Netherlands)); Schweikert, H.U. (Univ. of Bonn (Germany)); Zegers, N.D. (Medical Biological Laboratory-Organization for Applied Scientific Research, Rijswijk (Netherlands)); Hodgins, M.B. (Glasgow Univ. (United Kingdom))

    1990-10-01

    Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symtpoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. The authors report a G {r arrow} T mutation in the splice donor site of intron 4 of the androgen receptor gene of a 46, XY subject lacking detectable androgen binding to the receptor and with the complete form of androgen insensitivity. This point mutation completely abolishes normal RNA splicing at the exon 4/intron 4 boundary and results in the activation of a cryptic splice donor site in exon 4, which leads to the deletion of 123 nucleotides from the mRNA. Translation of the mutant mRNA results in an androgen receptor protein {approx}5 kDa smaller than the wild type. This mutated androgen receptor protein was unable to bind androgens and unable to activate transcription of an androgen-regulated reporter gene construct. This mutation in the human androgen receptor gene demonstrates the importance of an intact steroid-binding domain for proper androgen receptor functioning in vivo.

  15. Aberrant splicing of androgenic receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity

    International Nuclear Information System (INIS)

    Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symtpoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. The authors report a G → T mutation in the splice donor site of intron 4 of the androgen receptor gene of a 46, XY subject lacking detectable androgen binding to the receptor and with the complete form of androgen insensitivity. This point mutation completely abolishes normal RNA splicing at the exon 4/intron 4 boundary and results in the activation of a cryptic splice donor site in exon 4, which leads to the deletion of 123 nucleotides from the mRNA. Translation of the mutant mRNA results in an androgen receptor protein ∼5 kDa smaller than the wild type. This mutated androgen receptor protein was unable to bind androgens and unable to activate transcription of an androgen-regulated reporter gene construct. This mutation in the human androgen receptor gene demonstrates the importance of an intact steroid-binding domain for proper androgen receptor functioning in vivo

  16. The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids in rats.

    Science.gov (United States)

    Grönbladh, Alfhild; Johansson, Jenny; Kushnir, Mark M; Bergquist, Jonas; Hallberg, Mathias

    2013-12-11

    Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in sports communities. Several studies have suggested an association between GH and AAS. We have investigated the impact of GH in rats treated with nandrolone decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during three weeks and were subsequently treated with recombinant human GH (1.0I U/kg) for ten consecutive days. Plasma samples were collected and peripheral organs (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration of thirteen endogenous steroids was measured in the rat plasma samples using high specificity LC-MS/MS methods. Seven steroids were detected and quantified, and concentrations of estrone, testosterone, and androstenedione were significantly different among the groups, while concentrations of pregnenolone, DHEA, 17-hydroxyprogesterone and corticosterone were not altered. Administration of rhGH alone altered the plasma steroid distribution, and the results demonstrated significantly increased concentrations of plasma estrone as well as decreased concentrations of testosterone and androstenedione in the ND-treated rats. Administration of rhGH to ND-pretreated rats did not reverse the alteration of the steroid distribution induced by ND. Administration of ND decreased the weight of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH administration induced an enlargement of thymus. Taken together, the plasma steroid profile differed in the four groups, i.e. control, AAS, rhGH and the combination of AAS and rhGH treatment.

  17. Steroid osteopathy

    International Nuclear Information System (INIS)

    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

    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.

  19. Social modulation of androgen levels in male teleost fish.

    Science.gov (United States)

    Oliveira, Rui F; Hirschenhauser, Katharina; Carneiro, Luis A; Canario, Adelino V M

    2002-05-01

    Androgens are classically thought of as the sex steroids controlling male reproduction. However, in recent years evidence has accumulated showing that androgens can also be affected by the interactions between conspecifics, suggesting reciprocal interactions between androgens and behaviour. These results have been interpreted as an adaptation for individuals to adjust their agonistic motivation and to cope with changes in their social environment. Thus, male-male interactions would stimulate the production of androgens, and the levels of androgens would be a function of the stability of its social environment ['challenge hypothesis', Gen. Comp. Endocrinol. 56 (1984) 417]. Here the available data on social modulation of androgen levels in male teleosts are reviewed and some predictions of the challenge hypothesis are addressed using teleosts as a study model. We investigate the causal link between social status, territoriality and elevated androgen levels and the available evidence suggests that the social environment indeed modulates the endocrine axis of teleosts. The association between higher androgen levels and social rank emerges mainly in periods of social instability. As reported in the avian literature, in teleosts the trade-off between androgens and parental care is indicated by the fact that during the parental phase breeding males decreased their androgen levels. A comparison of androgen responsiveness between teleost species with different mating and parenting systems also reveals that parenting explains the variation observed in androgen responsiveness to a higher degree than the mating strategy. Finally, the adaptive value of social modulation of androgens and some of its evolutionary consequences are discussed. PMID:11997222

  20. 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 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.

  1. 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.

  2. 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.

  3. Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential.

    Science.gov (United States)

    Cadilla, Rodolfo; Turnbull, Philip

    2006-01-01

    Modulation of the androgen receptor has the potential to be an effective treatment for hypogonadism, andropause, and associated conditions such as sarcopenia, osteoporosis, benign prostatic hyperplasia, and sexual dysfunction. Side effects associated with classical anabolic steroid treatments have driven the quest for drugs that demonstrate improved therapeutic profiles. Novel, non-steroidal compounds that show tissue selective activity and improved pharmacokinetic properties have been developed. This review provides an overview of current advances in the development of selective androgen receptor modulators (SARMs).

  4. Anabolic steroids.

    Science.gov (United States)

    1995-05-01

    Testosterone, a naturally occurring tissue- and muscle-building anabolic steroid, is rapidly cleared by the liver and does not circulate in the body long enough to be useful as a treatment for wasting in AIDS patients. Lower doses of synthetic testosterone, while less rapidly cleared, tend to be toxic to the liver. Very high, continuous doses of anabolic steroids to treat wasting can cause peliosis hepatitis which can result in liver failure or stomach bleeding. Maintaining weight through the use of anabolic steroids requires eating foods rich in amino acids and protein sources and exercising, preferably using weights. Patients should consult with a nutritionist to help maintain a proper diet. In addition, if anabolic steroids are being used to maintain weight, the doctor should consider cycling the patient off the drug every 6 to 8 weeks as a safeguard against side effects. Those with questions about anabolic steroid treatment should contact Anabolics for AIDS at (213) 851-6734.

  5. [Bone and Men's Health. Bone selective androgen receptor modulators].

    Science.gov (United States)

    Furuya, Kazuyuki

    2010-02-01

    Androgen, one of the sex steroid hormones shows various biological activities on the corresponding various tissues. Many efforts to produce novel drug materials maintaining a desired biological activity with an adequate tissue selectivity, which is so-called selective androgen receptor modulators (SARMs) , are being performed. As one of such efforts, studies on SARMs against bone tissues which possess a significant potential to stimulate a bone formation with reducing undesirable androgenic virilizing activities are in progress all over the world. This review focuses on the research and development activities of such SARMs and discuses their usefulness for the treatment of osteoporosis.

  6. Protein-protein Interactions of the Androgen Receptor in Living Cells

    OpenAIRE

    Royen, Martin

    2008-01-01

    markdownabstract__Abstract__ Natural androgens, testosterone (T) and its derivative dihydrotestosterone (DHT) play a crucial role in the development and maintenance of the male phenotype. Androgens are steroids that exert their function via the androgen receptor (AR), a ligand dependent transcription factor. The human AR gene, is located on the X chromosome, and contains 8 exons, coding for a 110 kDa, 919 amino acids protein (Brinkmann et al., 1989; Hughes and Deeb, 2006). In the classical mo...

  7. Androgen insensitivity syndrome: gonadal androgen receptor activity

    International Nuclear Information System (INIS)

    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

  8. Mixtures of 17â-trenbolone with Ethinylestradiol or Bisphenol A Altered Tubercle Formation and Steroid Production in the Fathead Minnow

    Science.gov (United States)

    The xenoestrogens, ethinylestradiol (EE2) and bisphenol A (BPA), and the androgen 17â-trenbolone (TRB) are examples of endocrine disrupting compounds (EDCs) commonly detected in the environment. All have been shown to affect fish reproductive endocrinology individually, but littl...

  9. Vocal area-related expression of the androgen receptor in the budgerigar (Melopsittacus undulatus) brain.

    Science.gov (United States)

    Matsunaga, Eiji; Okanoya, Kazuo

    2008-05-01

    The androgen receptor is a steroid hormone receptor widely expressed in the vocal control nuclei in songbirds. Here, we analysed androgen receptor expression in the brains of juvenile and adult budgerigars. With a species-specific probe for budgerigar androgen receptor mRNA, we found that the androgen receptor was expressed in the vocal areas, such as the central nucleus of the lateral nidopallium, the anterior arcopallium, the oval nucleus of the mesopallium, the oval nucleus of the anterior nidopallium and the tracheosyringeal hypoglossal nucleus. With the present data, together with previous reports, it turned out that the androgen receptor expression in telencephalic vocal control areas is similar amongst three groups of vocal learners--songbirds, hummingbirds and parrots, suggesting the possibility that the androgen receptor might play a role in vocal development and that the molecular mechanism regulating the androgen receptor expression in the vocal areas might be important in the evolution of vocal learning.

  10. Androgen insensitivity syndrome

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001180.htm Androgen insensitivity syndrome To use the sharing features on this page, please enable JavaScript. Androgen insensitivity syndrome (AIS) is when a person who ...

  11. Ultra high performance liquid chromatography tandem mass spectrometry determination and profiling of prohibited steroids in human biological matrices. A review.

    Science.gov (United States)

    Gosetti, Fabio; Mazzucco, Eleonora; Gennaro, Maria Carla; Marengo, Emilio

    2013-05-15

    list of the prohibited substances of the World Anti-Doping Agency (WADA). In WADA list steroids figure in three main classes, namely anabolic steroids, corticosteroids and substances with anti-estrogenic properties. It must be strongly reminded that assumption of doping agents not only leads to athletes the possible failing of doping tests but causes important health risk and WADA prohibited list establishes criteria to highlight the alteration of the natural steroid profile caused by exogenous administration. Doping control analyses are generally performed in urine, a matrix that provides a prolonged detection time window, and less often in blood, serum, plasma, hair, saliva, and nails. To identify the chemical structures of anabolic steroids the use of mass spectrometry detection is very advantageous. Gas chromatography-mass spectrometry (GC-MS) techniques allowed for the development of comprehensive screening methods. GC-MS methods are sensitive and robust but present the disadvantages of time-consuming sample pretreatment, that is often based on hydrolysis and derivatisation reactions. Liquid chromatography-mass spectrometry (LC-MS) methods have been successfully used to identify and determinate steroids in different matrices, as well as to study their metabolisms. Nowadays, automatic rapid ultra high performance liquid chromatography (UHPLC) tandem mass spectrometry has become the technique of choice for steroid analysis. Due to its generally higher speed, sensitivity, reproducibility and specificity with respect to HPLC, it can be used to simultaneously separate and determinate multi component steroid mixtures. The technique is of huge interest to separate conjugates anabolic androgenic steroids, as it allows efficiency enhancement due to the small particle (sub-2μm) column packing, which provides high peak capacity within analysis times even 5-10 fold shorter than conventional HPLC methods. Modern multiplex instruments can analyze thousands of samples per month

  12. 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

  13. 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

    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 uti......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...

  14. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    Science.gov (United States)

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance.

  15. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    Science.gov (United States)

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. PMID:26849997

  16. A case of postmenopausal androgen excess.

    Science.gov (United States)

    Lambrinoudaki, Irene; Dafnios, Nikos; Kondi-Pafiti, Agathi; Triantafyllou, Nikos; Karopoulou, Evangelia; Papageorgiou, Anastasia; Augoulea, Areti; Armeni, Eleni; Creatsa, Maria; Vlahos, Nikolaos

    2015-10-01

    Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy. PMID:26287476

  17. DETERMINATION OF SIX ANABOLIC -ANDROGENIC STEROIDS IN BEEF MUSCLE TISSUES BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY%高效液相色谱法同时测定牛肉组织中6种类固醇类激素类药物

    Institute of Scientific and Technical Information of China (English)

    衣闻闻; 全灿; 金君素

    2011-01-01

    A HPLC method was established for the simultaneous determination of six anabolic - androgenic steroids including methandienone, nandrolone, boldenone, methyltestosterone, testosterone propionate and nantrolone propionate in beef muscle tissues. The samples were extracted with acetonitrile and then cleaned up by freezing - lipid filtration. The mobile phase consisted of methanol - water at flow rate of 1.0 Ml/min. The detection limits for the method were 0.0051-0.008 6 mg/kg, and the limits of quantification were 0. 0220 -0.0287 mg/kg. The linear calibration curves were obtained in the concentration range of 0. 25 - 10 mg/L, with r2 more than 0.999. The recoveries of the six compounds were 84. 1% - 100. 0% fortified at the 0.4 mg/kg and 2. 0 mg/kg levels, and the relative standard deviations of determination results were 0.5% -3.5%(n=5). The established method is simple, rapid, sensitive and specific, and it is appropriate for the identification and quantification of anabolic androgenic steroids in animal muscle tissues.%建立了高效液相色谱法同时测定牛肉组织中勃地龙、诺龙、美雄酮、甲基睾酮、丙酸睾酮和丙酸诺龙的分析方法.试样经乙腈提取,冷冻离心脱脂净化,以甲醇-水为流动相,梯度洗脱,流速为1.0 mL/min.该方法的检出限(LOD)为0.0051~0.0086 mg/kg,定量限(LOQ)为0.0220~0.0287 mg/kg,在0.25~10 mg/L的线性范围内,相关系数r2均大于0.999.在0.4 mg/kg和2.0 mg/kg的添加水平上,上述6种激素的平均回收率为84.1%~100.0%,测定结果的相对标准偏差为0.5%~3.5%(n=5).该方法的样品前处理简单、快速、稳定性好,可用于牛肉组织中上述6种蛋白同化类激素的同时测定.

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

    International Nuclear Information System (INIS)

    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

  19. Activation of PPAR by Rosiglitazone Does Not Negatively Impact Male Sex Steroid Hormones in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Mahmoud Mansour

    2009-01-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPAR activation decreased serum testosterone (T in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2 in female rats. This implies modulation of female sex steroid hormones by PPAR. It is not clear if PPAR modulates sex steroid hormones in diabetic males. Because PPAR activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPAR activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPAR activation on serum and intratesticular T, luteinizing hormone (LH, follicle stimulating hormone (FSH and E2 concentrations in male Zucker diabetic fatty (ZDF rats treated with the PPAR agonist rosiglitazone (a thiazolidinedione. Treatment for eight weeks increased PPAR mRNA and protein in the testis and elevated serum adiponectin, an adipokine marker for PPAR activation. PPAR activation did not alter serum or intratesticular T concentrations. In contrast, serum T level but not intratesticular T was reduced by diabetes. Neither diabetes nor PPAR activation altered serum E2 or gonadotropins FSH and LH concentrations. The results suggest that activation of PPAR by rosiglitazone has no negative impact on sex hormones in male ZDF rats.

  20. Drug Facts: Anabolic Steroids

    Science.gov (United States)

    ... Share Print Home » Publications » DrugFacts » Anabolic Steroids DrugFacts: Anabolic Steroids Email Facebook Twitter Revised March 2016 What are anabolic steroids? Anabolic steroids are synthetic variations of the male ...

  1. Hyperactive androgen receptor in prostate cancer, what does it mean for new therapy concepts?

    OpenAIRE

    Culig, Z.; Hobisch, A.; Hittmair, A; Radmayr, C.; Peterziel, H.; Bartsch, G; Cato, A. C. B.; Klocker, H

    1997-01-01

    Investigations on androgen signaling alterations in the late stages of prostate cancer revealed new molecular mechanisms that may be in part responsible for failure of endocrine therapy. Both primary and metastatic lesions from prostate cancer express androgen receptor protein. Amplification of androgen receptor gene occurs in a subset of prostate cancer patients. Several point mutations of androgen receptor gene have been described; they generate receptors whi...

  2. 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. PMID:26206424

  3. Intrauterine sexual differentiation: biosyntesis and action of sexual steroid hormones

    OpenAIRE

    Amilton Cesar dos Santos; Diego Carvalho Viana; Gleidson Benevides de Oliveira; Luis Miguel Lobo; Antônio Chaves Assis-Neto

    2015-01-01

    The objective of this review was to describe sexual differentiation events in mammals, relating them to biosynthesis of sexual steroid hormones and their mechanisms of action. Cholesterol is the precursor of sexual steroid hormone biosynthesis via action of several enzymes converting these hormones. Progestagens hormones serve as substrate for the production of androgens, which in turn serve as substrate for estrogen hormones. These hormones are responsible for sexual differentiation and repr...

  4. Effects of antiandrogens on transformation and transcription activation of wild-type and mutated (LNCaP) androgen receptors

    NARCIS (Netherlands)

    C.A. Berrevoets (Cor); J. Veldscholte (Jos); E. Mulder (Eppo)

    1993-01-01

    textabstractLNCaP cells contain androgen receptors with a mutation in the steroid binding domain (Thr 868 changed to Ala) resulting in a changed hormone specificity. Both the wild-type and mutated androgen receptors were transfected into COS cells. Transcription activation was studied in cells co-tr

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

    DEFF Research Database (Denmark)

    Gustavson, Lisa; Jenssen, Bjorn 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......-4 pathway in polar bears, similar to rodents. The large individual variability in steroid levels reported here most likely reflects the differences in reproductive status of the female polar bears during mating season. The steroid data establish reference values of steroid hormones and may...

  6. New method for labeling and autoradiographic localization of androgen receptors

    Energy Technology Data Exchange (ETDEWEB)

    Peters, C.A.; Barrack, E.R.

    1987-07-01

    We have used a novel receptor labeling and autoradiographic technique to localize androgen receptors in the intact rat ventral prostate at the morphological level. Frozen slide-mounted prostate tissue sections (10 micron thick) were incubated with increasing concentrations of (/sup 3/H)-R1881 in the absence and presence of excess unlabeled R1881. Tissue sections labeled in this way were subjected to concurrent biochemical and autoradiographic analysis. After incubation and washing to remove free (/sup 3/H)-steroid, some of the sections were wiped from the slides for scintillation counting in order to characterize and quantitate (/sup 3/H)-R1881 binding. Androgen receptors could indeed be labeled in slide-mounted tissue sections, and specific (/sup 3/H)-R1881 binding to these receptors was high-affinity (Kd = 1 nM), saturable, and androgen-specific. All cellular androgen receptors appear to be retained, because receptor content in sections was comparable to the sum of receptors in subcellular fractions of homogenized tissue. Replicate labeled slide-mounted tissue sections were dried rapidly, apposed to dry emulsion-coated coverslips, and exposed in the dark for autoradiography. Silver grains were counted over nuclei or cytoplasm of epithelium or stroma to evaluate specific androgen receptor location. Autoradiographic analysis demonstrated androgen receptor localization almost exclusively in the epithelial nuclei, with little or none in the stroma. We discuss here the unique features and advantages of labeling androgen receptors in slide-mounted frozen tissue sections for autoradiographic localization.

  7. New method for labeling and autoradiographic localization of androgen receptors

    International Nuclear Information System (INIS)

    We have used a novel receptor labeling and autoradiographic technique to localize androgen receptors in the intact rat ventral prostate at the morphological level. Frozen slide-mounted prostate tissue sections (10 micron thick) were incubated with increasing concentrations of [3H]-R1881 in the absence and presence of excess unlabeled R1881. Tissue sections labeled in this way were subjected to concurrent biochemical and autoradiographic analysis. After incubation and washing to remove free [3H]-steroid, some of the sections were wiped from the slides for scintillation counting in order to characterize and quantitate [3H]-R1881 binding. Androgen receptors could indeed be labeled in slide-mounted tissue sections, and specific [3H]-R1881 binding to these receptors was high-affinity (Kd = 1 nM), saturable, and androgen-specific. All cellular androgen receptors appear to be retained, because receptor content in sections was comparable to the sum of receptors in subcellular fractions of homogenized tissue. Replicate labeled slide-mounted tissue sections were dried rapidly, apposed to dry emulsion-coated coverslips, and exposed in the dark for autoradiography. Silver grains were counted over nuclei or cytoplasm of epithelium or stroma to evaluate specific androgen receptor location. Autoradiographic analysis demonstrated androgen receptor localization almost exclusively in the epithelial nuclei, with little or none in the stroma. We discuss here the unique features and advantages of labeling androgen receptors in slide-mounted frozen tissue sections for autoradiographic localization

  8. 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…

  9. Neuroactive steroids and their role in epilepsy

    OpenAIRE

    Chetan Y. Patil; Shamsundar A. Jadhav; Sudhakar M. Doifode; Mirza Shiraz Baig

    2012-01-01

    Neuroactive steroids are the certain steroids that alter neuronal excitability via the cell surface through interaction with certain neurotransmitter receptors. Neuroactive steroids regulate physiological functions of the central nervous system and have possible therapeutic potential in neurological diseases. They have been shown to affect neuronal excitability via their interaction with the ligand-gated ion channel family, such as the GABAA receptor by acting genomically as well as nongenomi...

  10. Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

    Science.gov (United States)

    Veldhuis, J D; Rogol, A D; Samojlik, E; Ertel, N H

    1984-07-01

    We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation. When the pure (nonaromatizable) androgen, 5-alpha-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition of LH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-17 beta did not change significantly, but serum 5 alpha-dihydrotestosterone concentrations increased approximately two- to threefold, with a corresponding increase in levels of its major metabolite, 5 alpha-androstan-3 alpha, 17 beta-diol. In separate experiments, the infusion of estradiol-17 beta at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-17 beta levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions. Our observations indicate that, despite the continuous infusion of a dosage of 5 alpha-dihydrotestosterone that significantly suppresses LH pulse frequency, co

  11. Steroid-bismetalloporphyrin as enzyme model of cytochrome P-450 monooxygenase

    Institute of Scientific and Technical Information of China (English)

    CHEN, Shu-Hua; LI, Shang-Jun; WANG, Yu-Liang

    2000-01-01

    The model compounds of androgenic steroid-bismetalloporphyrins 3a-3d and androgenic monometalloporphyrins 2a2d have been synthesized. Catalytic study in two-phase condition on epoxidation of styrene under the catalysis of model catalysts shows that the catalytic performances of steriod-bismetalloporphyrin is superior to steroid-metalloporphyrin and the corresponding simple metalloporphyrin. The excellent catalytic property of steriod-bismetalloporphyrin can be rationalized as the hydrophobic action of steroid framework and the cooperative action of two metalloporphyrins in catalysis.

  12. Sex Steroid Hormones and Reproductive Disorders : Impact on Women's Health

    NARCIS (Netherlands)

    Fauser, Bart C. J. M.; Laven, Joop S. E.; Tarlatzis, Basil C.; Moley, Kelle H.; Critchley, Hilary O. D.; Taylor, Robert N.; Berga, Sarah L.; Mermelstein, Paul G.; Devroey, Paul; Gianaroli, Luca; D'Hooghe, Thomas; Vercellini, Paolo; Hummelshoj, Lone; Rubin, Susan; Goverde, Angelique J.; De Leo, Vincenzo; Petraglia, Felice

    2011-01-01

    The role of sex steroid hormones in reproductive function in women is well established. However, in the last two decades it has been shown that receptors for estrogens, progesterone and androgens are expressed in non reproductive tissue /organs (bone, brain, cardiovascular system) playing a role in

  13. 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...

  14. 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.

    2012-01-01

    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 ad

  15. Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human Airway Smooth Muscle Cells.

    Science.gov (United States)

    Wang, Sheng-Yu; Freeman, Michelle R; Sathish, Venkatachalem; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

    2016-07-01

    Brain derived neurotropic factor (BDNF) is emerging as an important player in airway inflammation, remodeling, and hyperreactivity. Separately, there is increasing evidence that sex hormones contribute to pathophysiology in the lung. BDNF and sex steroid signaling are thought to be intricately linked in the brain. There is currently little information on BDNF and sex steroid interactions in the airway but is relevant to understanding growth factor signaling in the context of asthma in men versus women. In this study, we assessed the effect of sex steroids on BDNF expression and secretion in human airway smooth muscle (ASM). Human ASM was treated with estrogen (E2 ) or testosterone (T, 10 nM each) and intracellular BDNF and secreted BDNF measured. E2 and T significantly reduced secretion of BDNF; effects prevented by estrogen and androgen receptor inhibitor, ICI 182,780 (1 μM), and flutamide (10 μM), respectively. Interestingly, no significant changes were observed in intracellular BDNF mRNA or protein expression. High affinity BDNF receptor, TrkB, was not altered by E2 or T. E2 (but not T) significantly increased intracellular cyclic AMP levels. Notably, Epac1 and Epac2 expression were significantly reduced by E2 and T. Furthermore, SNARE complex protein SNAP25 was decreased. Overall, these novel data suggest that physiologically relevant concentrations of E2 or T inhibit BDNF secretion in human ASM, suggesting a potential interaction of sex steroids with BDNF in the airway that is different from brain. The relevance of sex steroid-BDNF interactions may lie in their overall contribution to airway diseases such as asthma. J. Cell. Physiol. 231: 1586-1592, 2016. © 2015 Wiley Periodicals, Inc. PMID:26566264

  16. Regulation of androgen action during establishment of pregnancy.

    Science.gov (United States)

    Gibson, Douglas A; Simitsidellis, Ioannis; Saunders, Philippa T K

    2016-07-01

    During the establishment of pregnancy, the ovarian-derived hormones progesterone and oestradiol regulate remodelling of the endometrium to promote an environment that is able to support and maintain a successful pregnancy. Decidualisation is characterised by differentiation of endometrial stromal cells that secrete growth factors and cytokines that regulate vascular remodelling and immune cell influx. This differentiation process is critical for reproduction, and inadequate decidualisation is implicated in the aetiology of pregnancy disorders such as foetal growth restriction and preeclampsia. In contrast to progesterone and oestradiol, the role of androgens in regulating endometrial function is poorly understood. Androgen receptors are expressed in the endometrium, and androgens are reported to regulate both the transcriptome and the secretome of endometrial stromal cells. In androgen-target tissues, circulating precursors are activated to mediate local effects, and recent studies report that steroid concentrations detected in endometrial tissue are distinct to those detected in the peripheral circulation. New evidence suggests that decidualisation results in dynamic changes in the expression of androgen biosynthetic enzymes, highlighting a role for pre-receptor regulation of androgen action during the establishment of pregnancy. These results suggest that such enzymes could be future therapeutic targets for the treatment of infertility associated with endometrial dysfunction. In conclusion, these data support the hypothesis that androgens play a beneficial role in regulating the establishment and maintenance of pregnancy. Future studies should be focussed on investigating the safety and efficacy of androgen supplementation with the potential for utilisation of novel therapeutics, such as selective androgen receptor modulators, to improve reproductive outcomes in women.

  17. SEX STEROIDS MODULATE UTERINE-PLACENTAL VASCULATURE: IMPLICATIONS FOR OBSTETRICS AND NEONATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Manuel eMaliqueo

    2016-04-01

    Full Text Available Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia and fetal growth restriction, exhibit altered sex steroid concentrations.

  18. EVALUATION OF STEROID HORMONES AND THEIR RECEPTORS IN DEVELOPMENT AND PROGRESSION OF RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Nigel Bennett

    2014-06-01

    Full Text Available Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC, with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

  19. Androgens and the breast.

    Science.gov (United States)

    Dimitrakakis, Constantine; Bondy, Carolyn

    2009-01-01

    Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation.

  20. 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

  1. Interactions of methoxyacetic acid with androgen receptor

    International Nuclear Information System (INIS)

    Endocrine disruptive compounds (EDC) alter hormone-stimulated, nuclear receptor-dependent physiological and developmental processes by a variety of mechanisms. One recently identified mode of endocrine disruption is through hormone sensitization, where the EDC modulates intracellular signaling pathways that control nuclear receptor function, thereby regulating receptor transcriptional activity indirectly. Methoxyacetic acid (MAA), the primary, active metabolite of the industrial solvent ethylene glycol monomethyl ether and a testicular toxicant, belongs to this EDC class. Modulation of nuclear receptor activity by MAA could contribute to the testicular toxicity associated with MAA exposure. In the present study, we evaluated the impact of MAA on the transcriptional activity of several nuclear receptors including the androgen receptor (AR), which plays a pivotal role in the development and maturation of spermatocytes. AR transcriptional activity is shown to be increased by MAA through a tyrosine kinase signaling pathway that involves PI3-kinase. In a combinatorial setting with AR antagonists, MAA potentiated the AR response without significantly altering the EC50 for androgen responsiveness, partially alleviating the antagonistic effect of the anti-androgens. Finally, MAA treatment of TM3 mouse testicular Leydig cells markedly increased the expression of Cyp17a1 and Shbg while suppressing Igfbp3 expression by ∼ 90%. Deregulation of these genes may alter androgen synthesis and action in a manner that contributes to MAA-induced testicular toxicity.

  2. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  3. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  4. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

    OpenAIRE

    Shtutman Michael; Tanner Matthew J; Carkner Richard D; Baghel Prateek S; Levina Elina; Feuerstein Michael A; Chen Mengqian; Vacherot Francis; Terry Stéphane; de la Taille Alexandre; Buttyan Ralph

    2010-01-01

    Abstract Background Castration resistant prostate cancer (CRPC) develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR) despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC....

  5. 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.

  6. 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.

  7. Sarcopenia and Androgens: A Link between Pathology and Treatment

    OpenAIRE

    Basualto-Alarcón, Carla; Varela, Diego; Duran, Javier; Maass, Rodrigo; Estrada, Manuel

    2014-01-01

    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 developme...

  8. 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, these things can reduce symptoms caused by high ...

  9. Anabolic steroids abuse and male infertility.

    Science.gov (United States)

    El Osta, Rabih; Almont, Thierry; Diligent, Catherine; Hubert, Nicolas; Eschwège, Pascal; Hubert, Jacques

    2016-01-01

    For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage.

  10. Anabolic steroids abuse and male infertility.

    Science.gov (United States)

    El Osta, Rabih; Almont, Thierry; Diligent, Catherine; Hubert, Nicolas; Eschwège, Pascal; Hubert, Jacques

    2016-01-01

    For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage. PMID:26855782

  11. The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

    International Nuclear Information System (INIS)

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

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

    International Nuclear Information System (INIS)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kajitani, Takashi; Tamamori-Adachi, Mimi [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan); Okinaga, Hiroko [Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan); Chikamori, Minoru; Iizuka, Masayoshi [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan); Okazaki, Tomoki, E-mail: okbgeni@med.teikyo-u.ac.jp [Department of Biochemistry, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan)

    2011-04-15

    Highlights: {yields} Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. {yields} Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. {yields} 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 {alpha}, 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.

  14. In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture

    International Nuclear Information System (INIS)

    PBDEs have been synthesized in large quantities as flame retardants for commercial products, such as electronic equipment and textiles. The rising in levels of PBDEs in tissues in wildlife species and in human milk and plasma samples over the past several years have raised concerns about possible health effects. Recently, we showed that the PBDE mixture, DE-71, delayed puberty and suppressed the growth of androgen-dependent tissues in male Wistar rat following a peri-pubertal exposure. These effects suggested that DE-71 may be either inducing steroid hormone metabolism or acting as an androgen receptor (AR) antagonist. To elucidate the potential anti-androgenic effects of this mixture, we evaluated DE-71 in several in vivo assays, which are responsive to alterations in androgen activity. In a pubertal exposure study designed to further evaluate the delay in preputial separation (PPS), we observed a dose-dependent delay in PPS with 60 and 120 mg/kg/day of DE-71 (4 and 5 days) and a corresponding suppression of ventral prostate (VP) and seminal vesicle growth at both doses. Adult males exposed to 60 mg/kg DE-71 for 3 days resulted in a significant increase in luteinizing hormone and a non-significant increase in testosterone, androstenedione and estrone. DE-71 also tested positive for anti-androgenic activity in an immature rat Hershberger assay, with decreases in mean VP and seminal vesicle weight following doses of 30-240 mg/kg. DE-71 and the individual BDE congeners which comprise the mixture (BDE-47, -99, -100, -153, -154) were also evaluated in vitro. First, AR binding was evaluated in a competitive binding assay using rat VP cytosol. In addition, we evaluated gene activation in a transcriptional activation assay using the MDA-kb2 cell line which contains an endogenous human AR and a transfected luciferase reporter. DE-71 and BDE-100 (2, 4, 6-pentaBDE) both inhibited AR binding, with IC50s of approximately 5 μM. In addition, DE-71 and two of the congeners (BDE

  15. Adolescent Steroid Use.

    Science.gov (United States)

    Office of Inspector General (DHHS), Washington, DC.

    The study focused on non-medical steroid use by adolescents according to data obtained from the National Institute on Drug Abuse, professional literature, 30 key informants knowledgeable in steroid issues, and 72 current or former steroid users. The findings indicated: (1) over 250,000 adolescents, primarily males, used or have used steroids, and…

  16. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Shtutman Michael

    2010-04-01

    Full Text Available Abstract Background Castration resistant prostate cancer (CRPC develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk between Hh and androgen signaling activities in androgen deprived and androgen independent (AI prostate cancer cells. Results Treatment of a variety of androgen-deprived or AI prostate cancer cells with the Hh inhibitor, cyclopamine, resulted in dose-dependent modulation of the expression of genes that are regulated by androgen. The effect of cyclopamine on endogenous androgen-regulated gene expression in androgen deprived and AI prostate cancer cells was consistent with the suppressive effects of cyclopamine on the expression of a reporter gene (luciferase from two different androgen-dependent promoters. Similarly, reduction of smoothened (Smo expression with siRNA co-suppressed expression of androgen-inducible KLK2 and KLK3 in androgen deprived cells without affecting the expression of androgen receptor (AR mRNA or protein. Cyclopamine also prevented the outgrowth of AI cells from androgen growth-dependent parental LNCaP cells and suppressed the growth of an overt AI-LNCaP variant whereas supplemental androgen (R1881 restored growth to the AI cells in the presence of cyclopamine. Conversely, overexpression of Gli1 or Gli2 in LNCaP cells enhanced AR-specific gene expression in the absence of androgen. Overexpressed Gli1/Gli2 also enabled parental LNCaP cells to

  17. Androgen regulation of the androgen receptor coregulators

    International Nuclear Information System (INIS)

    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

  18. Androgen regulation of the androgen receptor coregulators

    Directory of Open Access Journals (Sweden)

    Helenius Merja A

    2008-08-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

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

    International Nuclear Information System (INIS)

    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

  20. Steroid hormone receptors in prostatic hyperplasia and prostatic carcinoma.

    Science.gov (United States)

    Khalid, B A; Nurshireen, A; Rashidah, M; Zainal, B Y; Roslan, B A; Mahamooth, Z

    1990-06-01

    One hundred and six prostatic tissue samples obtained from transurethral resection were analysed for androgen and estrogen receptors. In 62 of these, progesterone and glucocorticoid receptors were also assayed. Steroid receptors were assayed using single saturation dose 3H-labelled ligand assays. Ninety percent of the 97 prostatic hyperplasia tissues and six of the nine prostatic carcinoma tissues were positive for androgen receptors. Estrogen receptors were only present in 19% and 33% respectively. Progesterone receptors were present in 70% of the tissues, but glucocorticoid receptors were present in only 16% of prostatic hyperplasia and none in prostatic carcinoma. PMID:1725553

  1. Stress and Androgen Activity During Fetal Development

    OpenAIRE

    Barrett, Emily S.; Swan, Shanna H.

    2015-01-01

    Prenatal stress is known to alter hypothalamic-pituitary-adrenal axis activity, and more recent evidence suggests that it may also affect androgen activity. In animal models, prenatal stress disrupts the normal surge of testosterone in the developing male, whereas in females, associations differ by species. In humans, studies show that (1) associations between prenatal stress and child outcomes are often sex-dependent, (2) prenatal stress predicts several disorders with notable sex difference...

  2. Identification of Comamonas testosteroni as an androgen degrader in sewage

    Science.gov (United States)

    Chen, Yi-Lung; Wang, Chia-Hsiang; Yang, Fu-Chun; Ismail, Wael; Wang, Po-Hsiang; Shih, Chao-Jen; Wu, Yu-Ching; Chiang, Yin-Ru

    2016-01-01

    Numerous studies have reported the masculinization of freshwater wildlife exposed to androgens in polluted rivers. Microbial degradation is a crucial mechanism for eliminating steroid hormones from contaminated ecosystems. The aerobic degradation of testosterone was observed in various bacterial isolates. However, the ecophysiological relevance of androgen-degrading microorganisms in the environment is unclear. Here, we investigated the biochemical mechanisms and corresponding microorganisms of androgen degradation in aerobic sewage. Sewage samples collected from the Dihua Sewage Treatment Plant (Taipei, Taiwan) were aerobically incubated with testosterone (1 mM). Androgen metabolite analysis revealed that bacteria adopt the 9, 10-seco pathway to degrade testosterone. A metagenomic analysis indicated the apparent enrichment of Comamonas spp. (mainly C. testosteroni) and Pseudomonas spp. in sewage incubated with testosterone. We used the degenerate primers derived from the meta-cleavage dioxygenase gene (tesB) of various proteobacteria to track this essential catabolic gene in the sewage. The amplified sequences showed the highest similarity (87–96%) to tesB of C. testosteroni. Using quantitative PCR, we detected a remarkable increase of the 16S rRNA and catabolic genes of C. testosteroni in the testosterone-treated sewage. Together, our data suggest that C. testosteroni, the model microorganism for aerobic testosterone degradation, plays a role in androgen biodegradation in aerobic sewage. PMID:27734937

  3. Intestinal parasite infections and fecal steroid levels in wild chimpanzees.

    Science.gov (United States)

    Muehlenbein, Michael P

    2006-08-01

    Immune-endocrine interactions have been evaluated much less frequently in nonhuman primates, and this may be due, in part, to logistical and ethical concerns regarding trapping and sampling of endangered species, especially apes. Using noninvasive fecal collection methods, the present study evaluates possible relationships between fecal steroid levels and gastrointestinal parasite infections in the Ngogo chimpanzee community in Kibale National Park, Uganda. Because both testosterone and cortisol exhibit immunosuppressive effects in vitro and in other animal models, it was hypothesized that both testosterone and cortisol would be positively associated with gastrointestinal parasite infections in these animals. When placed in a mixed model simultaneously, both testosterone (F = 4.98, df = 1, P = 0.033) and cortisol (F = 5.94, df = 1, P = 0.020) were positively associated with total (helminth and protozoan) parasite richness (the number of unique intestinal parasite species recovered from hosts' fecal samples). It is possible that androgens and corticoids alter the ability of a host to mount an effective immune response against concomitant infection with multiple parasitic species. The utility of fecal samples for assessing immune-endocrine interactions is discussed. PMID:16444733

  4. Overexpression of Androgen Receptors in Target Musculature Confers Androgen Sensitivity to Motoneuron Dendrites

    OpenAIRE

    Huguenard, Anna L.; Fernando, Shannon M.; Monks, D. Ashley; Sengelaub, Dale R.

    2010-01-01

    Androgen sensitivity of motoneuron dendrites is conferred indirectly via the enrichment of androgen receptors in the musculature in transgenic rats overexpressing androgen receptors in skeletal muscle.

  5. Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome.

    Science.gov (United States)

    Peterson, B S; Leckman, J F; Scahill, L; Naftolin, F; Keefe, D; Charest, N J; Cohen, D J

    1992-11-01

    We present our hypothesis that various steroid hormones play an important role in the symptom expression of Gilles de la Tourette's syndrome (TS) and that androgenic hormones, in particular, are likely to exacerbate symptoms of the disorder. We review the clinical evidence supporting our hypothesis. Sex steroids establish brain sexual dimorphisms early in CNS development, and we suggest mechanisms whereby androgenic and other hormonal changes later in human development might act at dimorphic brain regions to influence the natural history of TS. Finally, we discuss the various ways in which neuroendocrine studies might assist in genetic and neurobiologic research programs in TS.

  6. 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

  7. Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer

    NARCIS (Netherlands)

    Pfeiffer, M.J.; Smit, F.P.; Sedelaar, J.P.M.; Schalken, J.A.

    2011-01-01

    Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent t

  8. Androgen, estrogen and progesterone receptor expression in the human uterus during the menstrual cycle

    NARCIS (Netherlands)

    Mertens, HJMM; Heineman, MJ; Theunissen, PHMH; de Jong, FH; Evers, JLH

    2001-01-01

    Cyclic changes in steroid receptor expression in endometrial cells are considered a reflection of its differential functions. Besides estrogen and progestogens, androgens have also been suggested to affect the biological function of the female reproductive tract. We investigated the distribution and

  9. Steroid hormones as biomarkers of endocrine disruption in wildlife

    Energy Technology Data Exchange (ETDEWEB)

    Guillette, L.J. Jr.; Rooney, A.A.; Crain, D.A.; Orlando, E.F.

    1999-07-01

    Xenobiotic compounds introduced into the environment by human activity have been shown to adversely affect the endocrine system of wildlife. Various species exhibit abnormalities of (1) plasma sex steroid hormones, (2) altered steroid synthesis form the gonad in vitro and (3) altered steroidogenic enzyme function. These endpoints are sensitive and relatively easy to measure quantitatively with reliability and precision. These observations have led to the conclusion that sex steroid hormones could be markers of exposure to, and altered function from, endocrine disrupting contaminants (EDCs). However, there are serious limitations in the use of steroid hormones as generalized markers of EDC exposure. Steroid hormones exhibit seasonal, ontogenetic, gender and species-specific variation. Moreover, the regulation of sex steroid plasma concentrations is a relatively complex phenomenon capable of short-term (minutes-hours) alteration due to environmental inputs, such as acute stress--an activational response. Alterations in steroids synthesis and degradation also can be a response to altered embryonic development due to EDC exposure--an organizational response. If steroid hormones are to be used as biomarkers, then closely controlled, well designed sampling has to be performed. Additionally, an appreciation of the variation possible in endocrine responses among the species to be studied must be obtained.

  10. Histopathological alterations after a growth promoter boldenone injection in rabbits.

    Science.gov (United States)

    Tousson, Ehab

    2016-02-01

    Boldenone (BOL) is a derivative of the testosterone that has dual effects on humans, both directly and indirectly; directly as injection to build muscles and indirectly as through consuming meat of animals that where treated with BOL. However, the action of these steroids on different body organs structures is still unclear; therefore, the aim of the present study was to investigate the effect of the intramuscular injection of BOL undecylenate on the different organ structures. A total of 10 adult New Zealand rabbits were divided into two main groups, the first group was the control group, which includes animals that were injected intramuscularly with olive oil and the second group included animals that received two intramuscular injections of 5 mg/kg body weight BOL dissected after 6 weeks. Our results showed that intramuscular injection of rabbits with BOL showed hypertrophy in both skeletal and cardiac muscles, disturbances of the hepatocytes radially arranged cords with multifocal hepatocellular vacuolations in the liver, glomerulus mass reduction with multifocal glomerular injury in the kidney, disturbances of the cycle of spermatogenesis in the testes. In conclusion, using BOL, while preparing for a young bodybuilding contest, may cause an alteration in the histological structure of most of the body organs; these findings suggested that especially young people who misuse anablic androgenic steroids should be careful if they want to use such steroids to enhance their strength and endurance.

  11. Histopathological alterations after a growth promoter boldenone injection in rabbits.

    Science.gov (United States)

    Tousson, Ehab

    2016-02-01

    Boldenone (BOL) is a derivative of the testosterone that has dual effects on humans, both directly and indirectly; directly as injection to build muscles and indirectly as through consuming meat of animals that where treated with BOL. However, the action of these steroids on different body organs structures is still unclear; therefore, the aim of the present study was to investigate the effect of the intramuscular injection of BOL undecylenate on the different organ structures. A total of 10 adult New Zealand rabbits were divided into two main groups, the first group was the control group, which includes animals that were injected intramuscularly with olive oil and the second group included animals that received two intramuscular injections of 5 mg/kg body weight BOL dissected after 6 weeks. Our results showed that intramuscular injection of rabbits with BOL showed hypertrophy in both skeletal and cardiac muscles, disturbances of the hepatocytes radially arranged cords with multifocal hepatocellular vacuolations in the liver, glomerulus mass reduction with multifocal glomerular injury in the kidney, disturbances of the cycle of spermatogenesis in the testes. In conclusion, using BOL, while preparing for a young bodybuilding contest, may cause an alteration in the histological structure of most of the body organs; these findings suggested that especially young people who misuse anablic androgenic steroids should be careful if they want to use such steroids to enhance their strength and endurance. PMID:24097356

  12. Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines.

    Science.gov (United States)

    Wilson, Stephen; Qi, Jianfei; Filipp, Fabian V

    2016-01-01

    Sequence motifs are short, recurring patterns in DNA that can mediate sequence-specific binding for proteins such as transcription factors or DNA modifying enzymes. The androgen response element (ARE) is a palindromic, dihexameric motif present in promoters or enhancers of genes targeted by the androgen receptor (AR). Using chromatin immunoprecipitation sequencing (ChIP-Seq) we refined AR-binding and AREs at a genome-scale in androgen-insensitive and androgen-responsive prostate cancer cell lines. Model-based searches identified more than 120,000 ChIP-Seq motifs allowing for expansion and refinement of the ARE. We classified AREs according to their degeneracy and their transcriptional involvement. Additionally, we quantified ARE utilization in response to somatic copy number amplifications, AR splice-variants, and steroid treatment. Although imperfect AREs make up 99.9% of the motifs, the degree of degeneracy correlates negatively with validated transcriptional outcome. Weaker AREs, particularly ARE half sites, benefit from neighboring motifs or cooperating transcription factors in regulating gene expression. Taken together, ARE full sites generate a reliable transcriptional outcome in AR positive cells, despite their low genome-wide abundance. In contrast, the transcriptional influence of ARE half sites can be modulated by cooperating factors. PMID:27623747

  13. Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines

    Science.gov (United States)

    Wilson, Stephen; Qi, Jianfei; Filipp, Fabian V.

    2016-01-01

    Sequence motifs are short, recurring patterns in DNA that can mediate sequence-specific binding for proteins such as transcription factors or DNA modifying enzymes. The androgen response element (ARE) is a palindromic, dihexameric motif present in promoters or enhancers of genes targeted by the androgen receptor (AR). Using chromatin immunoprecipitation sequencing (ChIP-Seq) we refined AR-binding and AREs at a genome-scale in androgen-insensitive and androgen-responsive prostate cancer cell lines. Model-based searches identified more than 120,000 ChIP-Seq motifs allowing for expansion and refinement of the ARE. We classified AREs according to their degeneracy and their transcriptional involvement. Additionally, we quantified ARE utilization in response to somatic copy number amplifications, AR splice-variants, and steroid treatment. Although imperfect AREs make up 99.9% of the motifs, the degree of degeneracy correlates negatively with validated transcriptional outcome. Weaker AREs, particularly ARE half sites, benefit from neighboring motifs or cooperating transcription factors in regulating gene expression. Taken together, ARE full sites generate a reliable transcriptional outcome in AR positive cells, despite their low genome-wide abundance. In contrast, the transcriptional influence of ARE half sites can be modulated by cooperating factors. PMID:27623747

  14. Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines.

    Science.gov (United States)

    Wilson, Stephen; Qi, Jianfei; Filipp, Fabian V

    2016-09-14

    Sequence motifs are short, recurring patterns in DNA that can mediate sequence-specific binding for proteins such as transcription factors or DNA modifying enzymes. The androgen response element (ARE) is a palindromic, dihexameric motif present in promoters or enhancers of genes targeted by the androgen receptor (AR). Using chromatin immunoprecipitation sequencing (ChIP-Seq) we refined AR-binding and AREs at a genome-scale in androgen-insensitive and androgen-responsive prostate cancer cell lines. Model-based searches identified more than 120,000 ChIP-Seq motifs allowing for expansion and refinement of the ARE. We classified AREs according to their degeneracy and their transcriptional involvement. Additionally, we quantified ARE utilization in response to somatic copy number amplifications, AR splice-variants, and steroid treatment. Although imperfect AREs make up 99.9% of the motifs, the degree of degeneracy correlates negatively with validated transcriptional outcome. Weaker AREs, particularly ARE half sites, benefit from neighboring motifs or cooperating transcription factors in regulating gene expression. Taken together, ARE full sites generate a reliable transcriptional outcome in AR positive cells, despite their low genome-wide abundance. In contrast, the transcriptional influence of ARE half sites can be modulated by cooperating factors.

  15. Perturbation of the Hematopoietic Profile by Anabolic Androgenic Steroids

    Directory of Open Access Journals (Sweden)

    Jenny Erkander Mullen

    2014-01-01

    Full Text Available Objective. The aim of this study was to investigate the hematopoietic profile in AAS abusers, during or short after their last abuse and approximately six months later. Moreover, we studied if supraphysiological doses of testosterone influence the concentration of hemoglobin and erythropoietin in healthy volunteers. Design and Methods. Subjects (N=31 were recruited through an antidoping hotline. The hematological profile was measured when the subjects entered the study and approximately 6 months later. Testosterone enanthate (500 mg was administered to healthy volunteers (N=24. Gene expression was studied in human hek293 cells exposed to 1 μM testosterone. Results. Decreased levels of hemoglobin, erythrocyte volume fraction, and erythrocyte counts were observed after 6 months without the use of AAS. Results in volunteers show that hemoglobin increased 3% four and 15 days after testosterone administration, whereas EPO was significantly increased by 38% four days after dose. Agreeingly, in vitro study shows that testosterone induces the mRNA level of EPO with 65% after 24-hour exposure. Conclusion. These results indicate that supraphysiological doses of testosterone may cause a perturbation in the hematopoietic profile. This is of interest in relation to the adverse cardiovascular effects observed in AAS abusers.

  16. Effectiveness of Anabolic Steroid Preventative Intervention among Gym Users: Applying Theory of Planned Behavior

    OpenAIRE

    Abbas Moghimbeigi; Babak Moeini; Hamid Allahverdipour; Farzad Jalilian

    2011-01-01

    Background: Use of anabolic androgenic steroids (AAS) has been associated with adversephysical and psychiatric effects and it is known as rising problem among youth people. Thisstudy was conducted to evaluate anabolic steroids preventative intervention efficiency amonggym users in Iran and theory of planned behaviour was applied as theoretical framework.Methods: Overall, 120 male gym users participated in this study as intervention and controlgroup. This was a longitudinal randomized pretest ...

  17. ANABOLIC STEROIDS HAVE LONG-LASTING EFFECTS ON MALE SOCIAL BEHAVIORS

    OpenAIRE

    Salas-Ramirez, Kaliris Y.; Montalto, Pamela R.; Sisk, Cheryl L.

    2009-01-01

    Anabolic androgenic steroids (AAS) use by adolescents is steadily increasing. Adolescence involves remodeling of steroid-sensitive neural circuits that mediate social behaviors, and previous studies using animal models document effects of AAS on male social behaviors. The present experiments tested whether AAS have persistent and more pronounced behavioral consequences when drug exposure occurs during adolescence as compared to exposure in adulthood. Male Syrian hamsters were injected daily f...

  18. Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling

    Science.gov (United States)

    Montt-Guevara, Maria Magdalena; Shortrede, Jorge Eduardo; Giretti, Maria Silvia; Giannini, Andrea; Mannella, Paolo; Russo, Eleonora; Genazzani, Alessandro David; Simoncini, Tommaso

    2016-01-01

    The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen receptor (AR) is expressed in approximately 70 to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple-negative breast cancers. Recent studies have associated the actin-binding proteins of the ezrin–radixin–moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodeling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER), while the non-aromatizable androgen – DHT – only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer and, eventually, to develop new strategies for breast cancer treatment. PMID:27746764

  19. Di-(2 ethylhexyl phthalate and flutamide alter gene expression in the testis of immature male rats

    Directory of Open Access Journals (Sweden)

    Yu Frank H

    2009-09-01

    Full Text Available Abstract We previously demonstrated that the androgenic and anti-androgenic effects of endocrine disruptors (EDs alter reproductive function and exert distinct effects on developing male reproductive organs. To further investigate these effects, we used an immature rat model to examine the effects of di-(2 ethylhexyl phthalate (DEHP and flutamide (Flu on the male reproductive system. Immature male SD rats were treated daily with DEHP and Flu on postnatal days (PNDs 21 to 35, in a dose-dependent manner. As results, the weights of the testes, prostate, and seminal vesicle and anogenital distances (AGD decreased significantly in response to high doses of DEHP or Flu. Testosterone (T levels significantly decreased in all DEHP- treated groups, whereas luteinizing hormone (LH plasma levels were not altered by any of the two treatments at PND 36. However, treatment with DEHP or Flu induced histopathological changes in the testes, wherein degeneration and disorders of Leydig cells, germ cells and dilatation of tubular lumen were observed in a dose-dependent manner. Conversely, hyperplasia and denseness of Leydig, Sertoli and germ cells were observed in rats given with high doses of Flu. The results by cDNA microarray analysis indicated that 1,272 genes were up-regulated by more than two-fold, and 1,969 genes were down-regulated in response to DEHP, Flu or both EDs. These genes were selected based on their markedly increased or decreased expression levels. These genes have been also classified on the basis of gene ontology (e.g., steroid hormone biosynthetic process, regulation of transcription, signal transduction, metabolic process, biosynthetic process.... Significant decreases in gene expression were observed in steroidogenic genes (i.e., Star, Cyp11a1 and Hsd3b. In addition, the expression of a common set of target genes, including CaBP1, Vav2, Plcd1, Lhx1 and Isoc1, was altered following exposure to EDs, suggesting that they may be marker genes to

  20. Integrated multi-omics analyses reveal the biochemical mechanisms and phylogenetic relevance of anaerobic androgen biodegradation in the environment.

    Science.gov (United States)

    Yang, Fu-Chun; Chen, Yi-Lung; Tang, Sen-Lin; Yu, Chang-Ping; Wang, Po-Hsiang; Ismail, Wael; Wang, Chia-Hsiang; Ding, Jiun-Yan; Yang, Cheng-Yu; Yang, Chia-Ying; Chiang, Yin-Ru

    2016-08-01

    Steroid hormones, such as androgens, are common surface-water contaminants. However, literature on the ecophysiological relevance of steroid-degrading organisms in the environment, particularly in anoxic ecosystems, is extremely limited. We previously reported that Steroidobacter denitrificans anaerobically degrades androgens through the 2,3-seco pathway. In this study, the genome of Sdo. denitrificans was completely sequenced. Transcriptomic data revealed gene clusters that were distinctly expressed during anaerobic growth on testosterone. We isolated and characterized the bifunctional 1-testosterone hydratase/dehydrogenase, which is essential for anaerobic degradation of steroid A-ring. Because of apparent substrate preference of this molybdoenzyme, corresponding genes, along with the signature metabolites of the 2,3-seco pathway, were used as biomarkers to investigate androgen biodegradation in the largest sewage treatment plant in Taipei, Taiwan. Androgen metabolite analysis indicated that denitrifying bacteria in anoxic sewage use the 2,3-seco pathway to degrade androgens. Metagenomic analysis and PCR-based functional assays showed androgen degradation in anoxic sewage by Thauera spp. through the action of 1-testosterone hydratase/dehydrogenase. Our integrative 'omics' approach can be used for culture-independent investigations of the microbial degradation of structurally complex compounds where isotope-labeled substrates are not easily available. PMID:26872041

  1. Variations in urine excretion of steroid hormones after an acute session and after a 4-week programme of strength training.

    Science.gov (United States)

    Timón Andrada, Rafael; Maynar Mariño, M; Muñoz Marín, D; Olcina Camacho, G J; Caballero, M J; Maynar Mariño, J I

    2007-01-01

    Performing strength exercise, whether acutely or in a training programme, leads to alterations at the hypothalamic-pituitary-testicular and hypothalamic-pituitary-adrenal axes. One way to evaluate these changes is by analysis of the excretion of steroid hormones in the urine. The present study determined the variations in the urine profile of glucuroconjugated steroids after a single session of strength exercise and after a 4-week programme of strength training. The subjects were a group (n = 20) of non-sportsman male university students who worked out 3 days a week [Monday (M), Wednesday (W) and Friday (F)], performing the exercises at 70-75% of one repetition maximum strength (1-RM). Four urine samples were collected per subject: (A) before and (B) after a standard session prior to initiating the training programme, and (C) before and (D) after the same standard session at the end of the study, and they were assayed by gas chromatography coupled to mass spectrometry. The concentrations of the different hormones were determined relatively to the urine creatinine level (ng steroid/mg creatinine) to correct for diuresis. After the exercise sessions, both before and after the training programme, there was a fall in the urine excretion of androgens and estrogens, but no statistically significant changes in the excretion of tetrahydrocortisol (THF) and tetrahydrocortisone (THE). The anabolic/catabolic hormones ratio also decreased after the acute session, although only androstenodione + dehydroepiandrosterone (DHEA)/THE + THF ratio had a significant decrease (P < 0.05). After the training programme, there was a significant (P < 0.01) improvement in the strength of the muscle groups studied, and an increased urinary excretion of all the androgens with respect to the initial state of repose, with the difference being significant in the case of epitestosterone (Epit) (P < 0.05). The androsterone (A) + etiocholanolone (E)/THE + THF ratio increased significantly (P < 0

  2. 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...

  3. 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 have...... important biological roles in prepubertal children....

  4. Neuroactive steroids in depression and anxiety disorders: Clinical studies

    OpenAIRE

    Eser, Daniela; Schuele, Cornelius; Baghai, Thomas C.; Romeo, Elena; Rupprecht, Rainer

    2006-01-01

    Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant trea...

  5. Substitution of Ala564 in the first zinc cluster of the deoxyribonucleic acid (DNA)-binding domain of the androgen receptor by Asp, Asn, or Leu exerts differential effects on DNA binding

    NARCIS (Netherlands)

    H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); J.M. Lobaccaro; L. Chiche; C. Sultan; J. Trapman (Jan); A.O. Brinkmann (Albert)

    1998-01-01

    textabstractIn the androgen receptor of a patient with androgen insensitivity, the alanine residue at position 564 in the first zinc cluster of the DNA-binding domain was substituted by aspartic acid. In other members of the steroid receptor family, either valine or ala

  6. Activation of two mutant androgen receptors from human prostatic carcinoma by adrenal androgens and metabolic derivatives of testosterone.

    Science.gov (United States)

    Culig, Z; Stober, J; Gast, A; Peterziel, H; Hobisch, A; Radmayr, C; Hittmair, A; Bartsch, G; Cato, A C; Klocker, H

    1996-01-01

    The androgen receptor (AR) plays a central regulatory role in prostatic carcinoma and is a target of androgen ablation therapy. Recent detection of mutant receptors in tumor specimens suggest a contribution of AR alterations to progression towards androgen independence. In a specimen derived from metastatic prostate cancer we have reported a point mutation in the AR gene that leads to a single amino acid exchange in the ligand binding domain of the receptor. Another amino acid exchange resulting from a point mutation was also identified 15 amino acids away from our mutation. This mutation was detected in the AR gene isolated from an organ-confined prostatic tumor. Here we report the functional characterization of the two mutant receptors in the presence of adrenal androgens and testosterone metabolites. These studies were performed by cotransfecting androgen-responsive reporter genes and either the wild-type or mutant AR expression vectors into receptor negative DU-145 and CV-1 cells. The indicator genes used consisted of the promoter of the androgen-inducible prostate-specific antigen gene or the C' Delta9 enhancer fragment from the promoter of the mouse sex-limited protein driving the expression of the bacterial chloramphenicol acetyl transferase gene. Cotransfection-transactivation assays revealed that the adrenal androgen androstenedione and two products of testosterone metabolism, androsterone and androstandiol, induced reporter gene activity more efficiently in the presence of the mutant receptors than in the presence of the wild-type receptor. No difference between wild-type and mutant receptors was observed in the presence of the metabolite androstandione. The interaction of receptor-hormone complexes with target DNA was studied in vitro by electrophoretic mobility shift assays (EMSA). Dihydrotestosterone and the synthetic androgen mibolerone induced a faster migrating complex with all receptors, whereas the androgen metabolite androstandione induced this

  7. Sex steroids and bone: current perspectives.

    Science.gov (United States)

    Balasch, Juan

    2003-01-01

    Although the process of bone remodelling or its control has not yet been fully elucidated there is, at present, sufficient information available to conclude that ovarian steroids (estrogens, androgens, progesterone) play an essential role in skeletal homeostasis. The mechanism of action of sex steroids on the skeleton is still not entirely clear, but it has traditionally included indirect effects on systemic hormones that regulate calcium balance and a direct receptor-mediated action. More recently, changes in cytokine production within the bone marrow, as well as pro-apoptotic and anti-apoptotic effects in the osteoblastic cells, have been proposed as new perspectives on the cellular and molecular mechanisms by which sex steroids influence adult bone homeostasis. Mechanical loading, when combined with estrogens or androgens, results in a greater osteogenic response than either condition separately. Women are especially at risk for osteoporosis if they have had a premature or surgical menopause and have not received hormone replacement therapy (HRT). Other reproductive factors that can help to identify women with osteopenia and emphasize the role of sex steroids in preserving bone mass in premenopausal women include: age at menarche, menstrual history and irregularities (including those associated with excessive exercise), age at menopause, previous hysterectomy, hyperprolactinaemia, anorexia nervosa, scoliosis, ovarian dysgenesis, pregnancy and lactation, and pharmacological ovarian suppression. The prevention of osteoporosis starts with the onset of the menarche. A combination of exercise, appropriate nutrition and a healthy lifestyle all maximize bone mineral accrual and result in optimal peak bone mass; normal ovarian function is essential to this process. Unfortunately, many women actually become aware of the need for osteoporosis prevention much later in life, usually after they have already become menopausal. HRT, however, has important limitations for

  8. Steroid resistant asthma.

    Science.gov (United States)

    Luhadia, S K

    2014-03-01

    Inspite of very safe and effective treatment, Bronchial asthmatics do not respond well in 5-10% of cases which are labelled as Refractory Asthma. Besides compliance, presence of psychogenic and trigger factors and comorbid illness, steroid insensitiveness or resistance may play a significant role in the poorly controlled/responding asthmatics. Type I Steroid resistance is due to lack of binding affinity of steroids to glucocorticoid receptors and may respond to higher doses of steroids while type II steroid resistance is because of reduced number of cells with glucocorticoid receptors, which is very rare and do not respond to even higher doses of systemic steroids and these cases require alternative/novel therapies. Future treatment of steroid resistant and severe refractory asthma is likely to be targeted towards cytokines and Bronchial Thermoplasty.

  9. 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

  10. One and the same androgen for all? towards designer androgens

    Institute of Scientific and Technical Information of China (English)

    LouisJGGooren; NhuThanhNguyen

    1999-01-01

    The introduction of designer oestrogens as a treatment medality in hormone replacement in women has invited to consider the concept of compounds with selective androgenic effects for male honnone replacement therapy. The full spectrum of the actions of testosterone may not be necessary of even undesired for certain indications for testosterone treatment, To define for what indications certain androgenic properties are desired and undesired more insight in basic androgen (patho)physiology is required. There is convincing evidence that aromatization of androgenic compounds to nestrogens might be an advantage for maintenance of bone mass and it might also mitigate negative effects of androgens on bichemical parameters of cardiovascular risks: the potentially negative effects of oestmgens on prostate pathology in ageing men needs further elucidation. While the role of dihydro-testosterone (DHT) for the male sexual differentiation and for pubertal sexual maturation is evident, its role in mature and ageing males seems less significant or may even be harmful. It is, however, of note that a negative effect of DHT on prostate pathophysiolog~ is certainly not proven.For male contraception a progestational agent with strong androgenic properties might be an asset. For most of the androgenic actions the critical levels of androgens are not well established. The latter is relevant since the large amount of androgen molecules required for its biological actions (as compared to oestrogens) is an impediment in androgen replacement medalities. There may be room for more biopotent androgens since delivery of large amounts of androgen molecules to the circulation poses problems fur treatment modalities. ( Asian J Andro11999 Jun; 1:21 -28)

  11. Androgen receptor: structure, role in prostate cancer and drug discovery.

    Science.gov (United States)

    Tan, M H Eileen; Li, Jun; Xu, H Eric; Melcher, Karsten; Yong, Eu-leong

    2015-01-01

    Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. PMID:24909511

  12. Photoperiod and testosterone regulate androgen receptor immunostaining in the Siberian hamster brain.

    Science.gov (United States)

    Bittman, Eric L; Ehrlich, David A; Ogdahl, Justyne L; Jetton, Amy E

    2003-09-01

    Day length regulates the effects of gonadal steroids on gonadotropin secretion and behavior in seasonal breeders. To determine whether this influence of photoperiod results from changes in androgen receptor expression in Siberian hamster brain regions that regulate neuroendocrine function, androgen receptor immunostaining was examined in castrated animals given either no androgen replacement or one of three doses of testosterone (T) resulting in physiological serum concentrations. Half of the animals were housed under inhibitory photoperiod conditions, and immunostaining was quantified 11 days later. Measurement of serum gonadotropin and prolactin concentrations confirmed that androgen exerted graded effects on pituitary function but that the animals were killed before photoperiodic influences had fully developed. T significantly increased the numbers of androgen receptor-immunoreactive cells in every brain region examined. Photoperiod exerted no significant influence on androgen receptor-immunoreactive cell number in the arcuate nucleus, bed nucleus of the stria terminalis (BNST), medial preoptic nucleus, or in medial amygdala. An interaction between T and photoperiod was observed in the BNST and in the rostral and middle portions of the arcuate nucleus. Although increasing concentrations of T resulted in more intense cellular immunostaining in the BNST and arcuate, this effect was not influenced by day length. These results indicate that relatively short-duration (11 days) exposure to inhibitory photoperiod triggers localized and regionally specific changes in androgen receptor expression.

  13. The androgen receptor in hormone-refractory prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Lei Mao; Zhi-Qi Zhu; Charlie Degui Chen

    2009-01-01

    Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor (AR) signalling.However,the effect is short-lived,as nearly all tumours progress to a hormone-refractory (HR) state,a lethal stage of the disease.Intuitively,the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR turnouts.However,there is still a consensus that AR plays an essential role in HR prostate cancer (HRPC) because AR signalling is still functional in HR tumours.AR signalling can be activated in HR turnouts through several mechanisms.First,activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens.Also,mutations in the AR can change AR ligand specificity,thereby allowing it to be activated by non-steroids or anti-androgens.Finally,overexpression of the wild-type AR sensitizes itself to low concentrations of androgens.Therefore,drugs targeting AR signalling could still be effective in treating HRPC.

  14. Identification of the molecular switch that regulates access of 5α-DHT to the androgen receptor.

    OpenAIRE

    Penning, Trevor M.; Bauman, David R.; Jin, Yi; Rizner, Tea Lanisik

    2007-01-01

    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 3α-hydroxyst...

  15. Metabolic syndrome in androgenic alopecia

    OpenAIRE

    Hima Gopinath; Gatha M Upadya

    2016-01-01

    Background: Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. Aim: To study the association between metabolic syndrome and early-onset androgenic alopecia. Methods: A hospital-based analytical cross-sectional study was done on men in the age group of 18–55 years. Eighty five c...

  16. Control of adrenal androgen production.

    Science.gov (United States)

    Odell, W D; Parker, L N

    The major adrenal androgens are dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS) and androstenedione (delta 4). Studies by Cutler et al in 1978 demonstrated that these androgens are detectable in blood of all domestic and laboratory animals studied, but that only 4 species show increase in one or more with sexual maturation: rabbit, dog, chimpanzee and man. Studies by Grover and Odell in 1975 show these androgens do not bind to the androgen receptor obtained from rat prostate and thus probably are androgens only by conversion to an active androgen in vivo. Thomas and Oake in 1974 showed human skin converted DHEA to testosterone. The control of adrenal androgen secretion is in part modulated by ACTH. However, other factors or hormones must exist also, for a variety of clinical observations show dissociation in adrenal androgen versus cortisol secretion. Other substances that have been said to be controllers of adrenal androgen secretion include estrogens, prolactin, growth hormone, gonadotropins and lipotropin. None of these appear to be the usual physiological modulator, although under some circumstances each may increase androgen production. Studies from our laboratory using in vivo experiments in the castrate dog and published in 1979 indicated that crude extracts of bovine pituitary contained a substance that either modified ACTH stimulation of adrenal androgen secretion, or stimulated secretion itself - Cortisol Androgen Stimulating Hormone. Parker et al in 1983 showed a 60,000 MW glycoprotein was extractable from human pituitaries, which stimulated DHA secretion by dispersed canine adrenal cells in vitro, but did not stimulate cortisol secretion. This material contained no ACTH by radioimmunoassay. In 1982 Brubaker et al reported a substance was also present in human fetal pituitaries, which stimulated DHA secretion, but did not effect cortisol. PMID:6100259

  17. Self-Perceived Weight and Anabolic Steroid Misuse Among US Adolescent Boys

    Science.gov (United States)

    Jampel, Jonathan D.; Murray, Stuart B.; Griffiths, Scott; Blashill, Aaron J.

    2016-01-01

    Purpose Anabolic steroid misuse is a growing concern among adolescent boys, and chronic misuse is associated with multisystemic health consequences. However, little is known about weight related predictors of anabolic steroid misuse. We examined the prediction of lifetime anabolic steroid misuse as a function of self-perceived weight status among US adolescent boys. Methods Analysis was undertaken using the 2013 Youth Risk Behavior Survey, a nationally representative data set sampling public and private high school students throughout the United States. Data from a total of 6,000 US adolescent boys were used in the present study. Results The prevalence of ever misusing anabolic androgenic steroids was 12.6% among boys who viewed themselves as very underweight, 11.9% for boys who viewed themselves as very overweight, compared with 3.8% for boys who viewed themselves as about the right weight. Compared to boys who viewed themselves as about the right weight, boys who self-perceived themselves as very underweight (adjusted odds ratio = 6.9, 95% confidence interval: 2.7–17.7, p < .001) and very overweight (adjusted odds ratio = 3.8, 95% confidence interval: 1.8–7.7, p < .001) were significantly associated with increased risk of anabolic androgenic steroid misuse. Conclusions Large effect size estimates were revealed, suggesting that anabolic androgenic steroid misuse is not solely a function of boys desiring increased mass; boys who desire leanness are also likely to misuse anabolic androgenic steroids. Future prevention efforts should target not only boys who view themselves as underweight but also those who perceive themselves as overweight. PMID:26598061

  18. ANDROGEN INSENSITIVITY SYNDROME

    OpenAIRE

    Kanan; Sonali

    2014-01-01

    The condition is inherited as X - linked recessive gene 1 . The underlying pathology is the inability of end organs to respond to androgens. These cases are phenotypically and psychologically female with adequate breast development , normal external genitalia , a vagina with variable depth , absent /sparse pubic hair and axillary hair. The exact incidence in India is not known but the reported incidence is 1 in 2 , 000 to 1 in 62 ,400 worldwi...

  19. Applicability of a yeast bioassay in the detection of steroid esters in hair

    NARCIS (Netherlands)

    Becue, I.; Bovee, T.F.H.; Poucke, C.; Groot, M.J.; Nielen, M.W.F.; Peteghem, van C.

    2011-01-01

    The aim of the present study was to demonstrate the applicability of a yeast androgen and estrogen bioassay in the detection of steroid esters in hair samples of animals treated with a hormone ester cocktail. The outcome of the activity screenings was critically compared with the results previously

  20. 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.

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

    Science.gov (United States)

    Sveinsson, Olafur; Herrman, Lars

    2013-01-01

    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. PMID:23389726

  2. 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.

  3. Complete androgen insensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Tančić-Gajić Milina

    2015-01-01

    Full Text Available Introduction. Androgen insensitivity syndrome (AIS belongs to disorders of sex development, resulting from complete or partial resistance to the biological actions of androgens in persons who are genetically males (XY with normally developed testes and age-appropriate for males of serum testosterone concentration. Case Outline. A 21-year-old female patient was admitted at our Clinic further evaluation and treatment of testicular feminization syndrome, which was diagnosed at the age of 16 years. The patient had never menstruated. On physical examination, her external genitalia and breast development appeared as completely normal feminine structures but pubic and axillary hair was absent. Cytogenetic analysis showed a 46 XY karyotype. The values of sex hormones were as in adult males. The multisliced computed tomography (MSCT showed structures on both sides of the pelvic region, suggestive of testes. Bilateral orchiectomy was performed. Hormone replacement therapy was prescribed after gonadectomy. Vaginal dilatation was advised to avoid dyspareunia. Conclusion. The diagnosis of complete androgen insensitivity is based on clinical findigs, hormonal analysis karyotype, visualization methods and genetic analysis. Bilateral gonadectomy is generally recommended in early adulthood to avoid the risk of testicular malignancy. Vaginal length may be short requiring dilatation in an effort to avoid dyspareunia. Vaginal surgery is rarely indicated for the creation of a functional vagina. [Projekat Ministarstva nauke Republike Srbije, br. 175067

  4. The PPAR{gamma} ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V., E-mail: lstewart@mmc.edu

    2010-12-10

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPAR{gamma} ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPAR{gamma} ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPAR{gamma} ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPAR{gamma}. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPAR{gamma} and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

  5. Analysis of the molecular networks in androgen dependent and independent prostate cancer revealed fragile and robust subsystems.

    Directory of Open Access Journals (Sweden)

    Ryan Tasseff

    Full Text Available Androgen ablation therapy is currently the primary treatment for metastatic prostate cancer. Unfortunately, in nearly all cases, androgen ablation fails to permanently arrest cancer progression. As androgens like testosterone are withdrawn, prostate cancer cells lose their androgen sensitivity and begin to proliferate without hormone growth factors. In this study, we constructed and analyzed a mathematical model of the integration between hormone growth factor signaling, androgen receptor activation, and the expression of cyclin D and Prostate-Specific Antigen in human LNCaP prostate adenocarcinoma cells. The objective of the study was to investigate which signaling systems were important in the loss of androgen dependence. The model was formulated as a set of ordinary differential equations which described 212 species and 384 interactions, including both the mRNA and protein levels for key species. An ensemble approach was chosen to constrain model parameters and to estimate the impact of parametric uncertainty on model predictions. Model parameters were identified using 14 steady-state and dynamic LNCaP data sets taken from literature sources. Alterations in the rate of Prostatic Acid Phosphatase expression was sufficient to capture varying levels of androgen dependence. Analysis of the model provided insight into the importance of network components as a function of androgen dependence. The importance of androgen receptor availability and the MAPK/Akt signaling axes was independent of androgen status. Interestingly, androgen receptor availability was important even in androgen-independent LNCaP cells. Translation became progressively more important in androgen-independent LNCaP cells. Further analysis suggested a positive synergy between the MAPK and Akt signaling axes and the translation of key proliferative markers like cyclin D in androgen-independent cells. Taken together, the results support the targeting of both the Akt and MAPK

  6. Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

    Science.gov (United States)

    Ponzetto, Federico; Mehl, Florence; Boccard, Julien; Baume, Norbert; Rudaz, Serge; Saugy, Martial; Nicoli, Raul

    2016-01-01

    The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control

  7. Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

    Science.gov (United States)

    Ponzetto, Federico; Mehl, Florence; Boccard, Julien; Baume, Norbert; Rudaz, Serge; Saugy, Martial; Nicoli, Raul

    2016-01-01

    The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control

  8. Steroids in childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Ramachandrannair Rajesh

    2006-01-01

    Full Text Available Treatment of epileptic encephalopathies can be very challenging as most anticonvulsant drugs fail to achieve good seizure control. Steroids are disease modifying as well as anticonvulsant in these conditions. Though steroids are accepted as the first-line treatment for infantile spasms, there are many unanswered questions with regard to the preparation, dose and duration of treatment. In this review a re-exploration of the literature is attempted. Putative mechanism of action of steroids in infantile spasms is also discussed. As steroids are being increasingly used in other epileptic encephalopathies and Rasmussen′s encephalitis, a brief discussion on the role of steroids in these conditions is attempted. The review ends with the discussion on newer neuroactive steroids in the management of epilepsy.

  9. Hematological changes during androgen deprivation therapy

    Institute of Scientific and Technical Information of China (English)

    Mathis Grossmann; Jeffrey D Zajac

    2012-01-01

    Androgen deprivation therapy (ADT) has been associated with a plethora of adverse effects,consistent with the androgen dependency of multiple reproductive and somatic tissues.One such tissue is the hemopoietic system,and one of the most predictable consequences of ADT is the development of anemia.Although anemia caused by ADT is rarely severe,ADT is often given to frail,elderly men with increased susceptibility to anemia due to multiple other causes.ADT-associated anemia may contribute to fatigue and reduced quality of life (QoL) in such men,although this requires further study.While anemia is an independent risk factor of mortality in men with prostate cancer,it is not known whether treatment of ADT-associated anemia alters clinically important outcomes,or whether treatment affects mortality.Awareness of the phenomenon of ADT-induced anemia should avoid unnecessary work-up in mild cases of normocytic normochromic anemia.However,assessment and treatment of more severe anemia may be required.This should be determined on an individual basis.In contrast to the well-described actions of ADT on erythrepoiesis,its effect on other hemopoietic lineages has been less well elucidated.While preclinical studies have found roles for androgens in maturation and differentiated function of neutrophils,lymphocytes and platelets,the implications of these findings for men with prostate cancer receiving ADT require further studies.

  10. 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.

  11. Altered regulation of luteinizing hormone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

    Energy Technology Data Exchange (ETDEWEB)

    Bookstaff, R.C.

    1989-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) severely decreases plasma androgen concentrations, yet plasma luteinizing hormone (LH) concentrations remain unchanged. The mechanism by which TCDD prevents the expected compensatory increase in plasma LH was investigated. No effect on the plasma disappearance rate of LH or on pituitary capacity to synthesize or secrete LH was detected. Rather, TCDD altered the regulation of LH secretion by substantially increasing the potency of both androgens and estrogens as feedback inhibitors of LH secretion. The mechanism by which TCDD alters androgen-regulated LH secretion was further investigated. Seven days after dosing, TCDD decreased plasma testosterone concentrations but prevented the expected compensatory increases in pituitary gonadotropin-releasing hormone (GnRH) receptor number, pituitary responsiveness to GnRH, and plasma LH concentrations as seen in similarly hypoandrogenic vehicle dosed rats. Furthermore, the TCDD dose-response relationships for preventing the compensatory increases in pituitary GnRH receptor number and plasma LH concentration were similar. However, in the absence of gonadal steroids (7 days after castration) TCDD did not affect the compensatory increases in pituitary GnRH receptor number, pituitary responsiveness to GnRH, or plasma LH concentration. All of these parameters increased substantially relative to intact TCDD treated rats, and to levels virtually identical to those seen in castrated control rats. Treatment of castrated rats with testosterone restored the ability of TCDD to prevent these compensatory increases. Taken together, these results demonstrate that the presence of androgens is required for TCDD to alter the regulation of pituitary GnRH receptors.

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

    International Nuclear Information System (INIS)

    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

  13. Crystallization and preliminary X-ray analysis of the human androgen receptor ligand-binding domain with a coactivator-like peptide and selective androgen receptor modulators

    International Nuclear Information System (INIS)

    The human androgen receptor ligand-binding domain has been crystallized as a ternary complex with a coactivator-like undecapeptide and two different synthetic ligands. The ligand-binding domain of the human androgen receptor has been cloned, overproduced and crystallized in the presence of a coactivator-like 11-mer peptide and two different nonsteroidal ligands. The crystals of the two ternary complexes were isomorphous and belonged to space group P212121, with one molecule in the asymmetric unit. They diffracted to 1.7 and 1.95 Å resolution, respectively. Structure determination of these two complexes will help in understanding the mode of binding of selective nonsteroidal androgens versus endogenous steroidal ligands and possibly the origin of their tissue selectivity

  14. Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Nlicole M Martin; Barham K Abu Dayyeh; Raymond T Chung

    2008-01-01

    Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half alter his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery.This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.

  15. Rapid steroid hormone actions via membrane receptors.

    Science.gov (United States)

    Schwartz, Nofrat; Verma, Anjali; Bivens, Caroline B; Schwartz, Zvi; Boyan, Barbara D

    2016-09-01

    Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17β-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects. PMID:27288742

  16. Androgens affect muscle, motor neuron, and survival in a mouse model of SOD1-related amyotrophic lateral sclerosis.

    Science.gov (United States)

    Aggarwal, Tanya; Polanco, Maria J; Scaramuzzino, Chiara; Rocchi, Anna; Milioto, Carmelo; Emionite, Laura; Ognio, Emanuela; Sambataro, Fabio; Galbiati, Mariarita; Poletti, Angelo; Pennuto, Maria

    2014-08-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of upper and lower motor neurons and skeletal muscle atrophy. Epidemiologic and experimental evidence suggest the involvement of androgens in ALS pathogenesis, but the mechanism through which androgens modify the ALS phenotype is unknown. Here, we show that androgen ablation by surgical castration extends survival and disease duration of a transgenic mouse model of ALS expressing mutant human SOD1 (hSOD1-G93A). Furthermore, long-term treatment of orchiectomized hSOD1-G93A mice with nandrolone decanoate (ND), an anabolic androgenic steroid, worsened disease manifestations. ND treatment induced muscle fiber hypertrophy but caused motor neuron death. ND negatively affected survival, thereby dissociating skeletal muscle pathology from life span in this ALS mouse model. Interestingly, orchiectomy decreased androgen receptor levels in the spinal cord and muscle, whereas ND treatment had the opposite effect. Notably, stimulation with ND promoted the recruitment of endogenous androgen receptor into biochemical complexes that were insoluble in sodium dodecyl sulfate, a finding consistent with protein aggregation. Overall, our results shed light on the role of androgens as modifiers of ALS pathogenesis via dysregulation of androgen receptor homeostasis.

  17. Synthesis and chemical reactions of the steroidal hormone 17α-methyltestosterone.

    Science.gov (United States)

    El-Desoky, El-Sayed Ibrahim; Reyad, Mahmoud; Afsah, Elsayed Mohammed; Dawidar, Abdel-Aziz Mahmoud

    2016-01-01

    Structural modifications of natural products with complex structures like steroids require great synthetic effort. A review of literature is presented on the chemistry of the steroidal hormone 17α-methyltestosterone that is approved by Food and Drug Administration (FDA) in the United States as an androgen for estrogen-androgen hormone replacement therapy treatment. The analog also offers special possibilities for the prevention/treatment of hormone-sensitive cancers. The testosterone skeleton has important functionalities in the molecule that can act as a carbonyl component, an active methylene compound, α,β-unsaturated enone and tertiary hydroxyl group in various chemical reactions to access stereoisomeric steroidal compounds with potent activity. In addition, microbiological methods of synthesis and transformation of this hormone are presented.

  18. Regucalcin Expression as a Diagnostic Tool for the Illicit Use of Steroids in Veal Calves.

    Science.gov (United States)

    Starvaggi Cucuzza, Laura; Biolatti, Bartolomeo; Sereno, Alessandra; Cannizzo, Francesca T

    2015-06-17

    It has been previously demonstrated that sex steroid hormone treatment down-regulates regucalcin gene expression in the accessory sex glands and testis of prepubertal and adult male bovines. The aim of this study was to investigate whether low doses of sex steroid hormones combined with other drugs significantly affect regucalcin gene expression in the accessory sex glands and testis of veal calves. The regucalcin expression was down-regulated in the bulbo-urethral glands of estrogen-treated calves, whereas it was up-regulated in the prostate of estrogen-treated calves. Only the testis of androgen-treated calves showed a down-regulation of the regucalcin expression. Thus, the administration of sex steroid hormones, even in low doses and combined with other molecules, could affect regucalcin expression in target organs. Particularly, the specific response in the testis suggests regucalcin expression in this organ as a first molecular biomarker of illicit androgen administration in bovine husbandry. PMID:26016660

  19. Synthesis and chemical reactions of the steroidal hormone 17α-methyltestosterone.

    Science.gov (United States)

    El-Desoky, El-Sayed Ibrahim; Reyad, Mahmoud; Afsah, Elsayed Mohammed; Dawidar, Abdel-Aziz Mahmoud

    2016-01-01

    Structural modifications of natural products with complex structures like steroids require great synthetic effort. A review of literature is presented on the chemistry of the steroidal hormone 17α-methyltestosterone that is approved by Food and Drug Administration (FDA) in the United States as an androgen for estrogen-androgen hormone replacement therapy treatment. The analog also offers special possibilities for the prevention/treatment of hormone-sensitive cancers. The testosterone skeleton has important functionalities in the molecule that can act as a carbonyl component, an active methylene compound, α,β-unsaturated enone and tertiary hydroxyl group in various chemical reactions to access stereoisomeric steroidal compounds with potent activity. In addition, microbiological methods of synthesis and transformation of this hormone are presented. PMID:26639430

  20. 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.

  1. Hypothalamic expression of oestrogen receptor α and androgen receptor is sex-, age- and region-dependent in mice

    NARCIS (Netherlands)

    Brock, O; De Mees, C; Bakker, J

    2015-01-01

    Sex steroid hormones act on developing neural circuits regulating the hypothalamic-pituitary-gonadal axis and are involved in hormone-sensitive behaviours. These hormones act mainly via nuclear receptors, such as oestrogen receptor (ER)-α and androgen receptor (AR). By using immunohistochemistry, we

  2. [7α-18F]fluoro-17α-methyl-5α-dihydrotestosterone: a ligand for androgen receptor-mediated imaging of prostate cancer

    International Nuclear Information System (INIS)

    We have synthesized a 18F-labeled androgen, [7α-18F]fluoro-17α-methyl-5α-dihydrotestosterone, in a no-carrier-added radiosynthesis by exchange of 18F- (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-18F-androgen concentrates markedly in the prostate of rats by an androgen receptor-dependent mechanism. It is likely that [7α-18F]fluoro-17α-methyl-5α-dihydrotestosterone will be an excellent positron emission tomography imaging agent for prostate cancer

  3. Metabolic syndrome in androgenic alopecia

    Directory of Open Access Journals (Sweden)

    Hima Gopinath

    2016-01-01

    Full Text Available Background: Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. Aim: To study the association between metabolic syndrome and early-onset androgenic alopecia. Methods: A hospital-based analytical cross-sectional study was done on men in the age group of 18–55 years. Eighty five clinically diagnosed cases with early-onset (<35 years androgenic alopecia of Norwood grade III or above, and 85 controls without androgenic alopecia were included. Data collected included anthropometric measurements, arterial blood pressure and history of chronic diseases. Fasting blood and lipid profile were determined. Metabolic syndrome was diagnosed as per the new International Diabetes Federation criteria. Chi-square and Student's t-test were used for statistical analysis using Statistical Package for the Social Sciences (SPSS version 17.00. Results: Metabolic syndrome was seen in 19 (22.4% patients with androgenic alopecia and 8 (9.4% controls (P = 0.021. Abdominal obesity, hypertension and lowered high-density lipoprotein were significantly higher in patients with androgenic alopecia versus their respective controls. Limitations: The limitations of our study include small sample size in subgroups and the lack of evidence of a temporal relationship between metabolic syndrome and androgenic alopecia. Conclusion: A higher prevalence of metabolic syndrome is seen in men with early-onset androgenic alopecia. Early screening for metabolic syndrome and its components is beneficial in patients with early-onset androgenic alopecia.

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

    International Nuclear Information System (INIS)

    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 10-9M) and in a saturable manner. The number of binding sites was comparable to that for 5α-dihydrotestosterone (5α-DHT). [3H]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 [3H]-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 [3H]TSAA-291 was examined, specific binding of [3H]TSAA-291 was observed in fractions corresponding to 8-10 S. Binding of the [3H]TSAA-291-macromolecules comples to prostatic nuclei and DNA-cellulose was considerably less than binding by the [3H]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)

  5. 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.

  6. 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...... open dose-ranging study. As no significant tolerability issues were reported, further investigation of Casodex at these higher doses is in progress. All studies in which Casodex has been investigated have shown it to be a well-tolerated anti-androgen with a good side-effect profile compared with those...... reported for other available non-steroidal anti-androgens....

  7. Contributions of androgen and estrogen to fetal programming of ovarian dysfunction

    Directory of Open Access Journals (Sweden)

    Dumesic Daniel A

    2006-04-01

    Full Text Available Abstract In female mammals, including humans, deviations from normal androgenic or estrogenic exposure during fetal development are detrimental to subsequent adult ovarian function. Androgen deficiency, without accompanying estrogen deficit, has little apparent impact on ovarian development. Fetal estrogen deficiency, on the other hand, results in impaired oocyte and follicle development, immature and abnormal adult ovaries, and excessive ovarian stimulation from endogenous gonadotropins ultimately generating hemorrhagic follicles. Complete estrogen deficiency lasting into adulthood results in partial ovarian masculinization. Fetal androgen excess, on the other hand, mediated either by direct androgen action or following androgen aromatization to estrogen, reprograms ovarian development and reproductive neuroendocrinology to mimic that found in women with polycystic ovary syndrome: enlarged, polyfollicular, hyperandrogenic, anovulatory ovaries with accompanying LH hypersecretion. Oocyte developmental competence is also compromised. Insulin is implicated in the mechanism of both anovulation and deficient oocyte development. Fetal estrogen excess induces somewhat similar disruption of adult ovarian function to fetal androgen excess. Understanding the quality of the fetal female sex steroid hormone environment is thus becoming increasingly important in improving our knowledge of mechanisms underlying a variety of female reproductive pathologies.

  8. Androgens and sexuality.

    Science.gov (United States)

    Hutchinson, K A

    1995-01-16

    A review of the literature reveals that the endocrine determinants of female sexuality are complex and difficult to characterize. In adolescent males, free testosterone directly affects sexual motivation, with social factors exerting little or no effect. In adolescent girls, by contrast, societal and peer pressure play a pivotal role in the appearance of certain sexual behaviors. Throughout a woman's life, hormonal and psychosocial factors are critical influences. It is possible that cyclic patterns of testosterone are less important for female sexual behavior than the "tonic" effect of overall testosterone levels. Although the estrogen dependence of the vaginal epithelium--important for postmenopausal women--has been clearly established, the role of other hormonal factors and treatments, particularly those involving androgens, in human female sexual behavior remains enigmatic. The search for an understanding of these relationships is not merely an interesting academic exercise but is necessary to determine what role, if any, androgens may play in the treatment of sexual dysfunction during the female reproductive years. PMID:7825630

  9. Androgen and prostatic stroma

    Institute of Scientific and Technical Information of China (English)

    Yuan-JieNIU; Teng-XiangMA; IuZHANG; YongXU; Rui-FaHAN; GuangSUN

    2003-01-01

    Aim:To investigate the effect of androgen on the proliferation,differentiation and regression of canine prostatic stromal cells in vivo and human stromal cells in vitro.Methods:Twenty-two dogs,including 15 normal prostate doge and 7 prostatic hyperplasia dogs,had their serum concentration of testosterone and estrodiol determined by radioimmunoassay before and after castration.The expression of androgen receptor(AR)and estrogen receptor(ER)in the prostate were analysed by immunohistochemistry and semi-quantitative RT-PCR before and after castration.Light microscopy,transmission electron microscopy and TUNEL assay were carried out successively before and after castration to evaluate the prostatic histomorphology.In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone(DHT).The proliferation of the cell culture was detected by MTT assay.The expression of TGFβ bFGF,AR,and smooth muscle cell(SMC) specific proteins (myosin and/or smoothelin)were detected using immunohistochemistry and RT-PCR.The differentiation from fibroblasts to smooth muscle cells was deduced by measuring the expression of SMC specific proteins.Results:Before castration,the serum concentrations of testosterone and estrodiol were not statistically different between normal and hyperplasia groups.Following castration,the serum concentration of testerone decreased rapidly in 2 days,and the concentration of estrodiol had no significant change compared with the pre-castration data.In the prostate,AR was presented in both the epithelial and stromal cells and the AR mRNA level was higher in hyperplasia than in normal prostate tissues(P<0.05).While ER predominantly existed in the prostate stromal cells and the ER mRNA had no difference between the hyperplasia and the normal group.Within the early phase of castration(

  10. [Osteoporosis in men and androgen replacement therapy].

    Science.gov (United States)

    Tsujimura, Akira; Okuyama, Akihiko

    2003-11-01

    Androgen plays an important role in bone maturation and maintenance of bone mass. Androgen deficiency associated with aging causes osteoporosis for men. With respect to this disease, androgen replacement treatment has been performed for aging male. However, available preparations of androgen are limited in Japan and each of them has both merit and demerit. Establishment of guideline for androgen replacement treatment including criteria of serum testosterone concentration is the problem, which now confronts us. PMID:15775234

  11. Oral contraceptives as anti-androgenic treatment of acne.

    Science.gov (United States)

    Lemay, André; Poulin, Yves

    2002-07-01

    Although acne is seldom associated with high serum levels of androgens, it has been shown that female acne patients have definite increases in ovarian and adrenal androgen levels when compared to appropriate controls. As shown in several pilot and in multiple open and comparative studies, oral contraceptives (OCs) are effective in causing a significant regression of mild to moderate acne. These results have been confirmed by multicentre randomized trials where low-dose OCs did not cause side effects different from those of the placebo-controlled group. The beneficial effect of OCs is related to a decrease in ovarian and adrenal androgen precursors; to an increase in sex hormone-binding globulin (SHBG), which limits free testosterone; and to a decrease in 3a-androstenediol glucuronide conjugate, the catabolite of dihydrotestosterone (DHT) formed in peripheral tissues. The estrogen-progestin combination containing cyproterone acetate (CPA) is particularly effective in treating acne, since this progestin also has a direct peripheral anti-androgenic action in blocking the androgen receptor. Only two open studies and one randomized study on small numbers of patients have reported some efficacy of spironolactone used alone or in combination with an OC in the treatment of acne. The new non-steroidal anti-androgens flutamide and finasteride are being evaluated for the treatment of hirsutism. Oral antibiotics are prescribed to patients with inflammatory lesions, where they are effective in decreasing the activity of microbes, the activity of microbial enzymes, and leukocyte chemotaxis. Concomitant intake of an OC and an antibiotic usually prescribed for acne does not impair the contraceptive efficacy of the OC. A second effective contraceptive method should be used whenever there would be decreased absorption or efficacy of the OC (digestive problems, breakthrough bleeding), lack of compliance and use of a type or dose of antibiotic different from that usually prescribed

  12. In vivo modulation of androgen receptor by androgens

    Institute of Scientific and Technical Information of China (English)

    V·L·Kumar; V·Kumar

    2002-01-01

    Aim:To study the effect of androgen and antiandrogen on the level of androgen receptor(AR)mRNA.Methods:The totalRNA was extracted from the prostate and analyzed by slot blot analysis,The blots were hybrid-ized with ARcDNA probe and 1Aprobe(internal control)and autoradionraphy was performed.The intensity of signal was measured with a densitometer and the ratio of AR RNAand1ARNAwas calculated.Results:Androgenic deprivation produced by castration decreased the weight of the prostate and increased the levels of ARmRNA.Treatment of the castrated rats with testostrone increased the weight of prostate and decreased the levels of ARmRNA.Treatment of normal rats with flutamide decreased the weight of the gland and increased the levels of AR mRNA.Conclusion:Androgens produce proliferative effect on the prostate and negatively regulate the AR transcription.

  13. [Cardiovascular alterations associated with doping].

    Science.gov (United States)

    Thieme, D; Büttner, A

    2015-05-01

    Doping -the abuse of anabolic-androgenic steroids in particular- is widespread in amateur and recreational sports and does not solely represent a problem of professional sports. Excessive overdose of anabolic steroids is well documented in bodybuilding or powerlifting leading to significant side effects. Cardiovascular damages are most relevant next to adverse endocrine effects.Clinical cases as well as forensic investigations of fatalities or steroid consumption in connection with trafficking of doping agents provide only anecdotal evidence of correlations between side effects and substance abuse. Analytical verification and self-declarations of steroid users have repeatedly confirmed the presumption of weekly dosages between 300 and 2000 mg, extra to the fact that co-administration of therapeutics to treat side-effects represent a routine procedure. Beside the most frequent use of medications used to treat erectile dysfunction or estrogenic side-effects, a substantial number of antihypertensive drugs of various classes, i.e. beta-blockers, diuretics, angiotensin II receptor antagonists, calcium channel blockers, as well as ACE inhibitors were recently confiscated in relevant doping cases. The presumptive correlation between misuse of anabolic steroids and self-treatment of cardiovascular side effects was explicitly confirmed by detailed user statements.Two representative fatalities of bodybuilders were introduced to outline characteristic, often lethal side effects of excessive steroid abuse. Moreover, illustrative autopsy findings of steroid acne, thrombotic occlusion of Ramus interventricularis anterior and signs of cardiac infarctions are presented.A potential steroid abuse should be carefully considered in cases of medical consultations of patients exhibiting apparent constitutional modifications and corresponding adverse effects. Moreover, common self-medications -as frequently applied by steroid consumers- should be taken into therapeutic considerations

  14. Common molecular weight of the androgen receptor monomer in different target tissues

    International Nuclear Information System (INIS)

    Previously reported molecular weights for the monomeric steroid binding subunit of the androgen receptor protein have ranged from 25,000 to 167,000. The molecular weight appeared to vary among different species and target organs, as well as between different investigators. This study has examined androgen receptors from a diverse group of organs and species to determine whether these tissues share a common monomeric form. Gel filtration revealed peaks of specific [3H]dihydrotestosterone binding activity corresponding to Stokes radii of 54, 33, and 20 A in cytosols from several tissues. Phosphocellulose chromatography diminished the appearance of the smaller androgen receptor forms and facilitated the appearance of the larger 54-A form. Mixing experiments suggested that phosphocellulose was stabilizing the 54-A form by binding putative proteases which cleave this larger form. Methods were developed to generate homogeneous preparations of a given androgen receptor size for comparative study. Sucrose density gradient analysis showed sedimentation coefficients of 4.5-5.0, 3.5-4.0, and 2.5-3.0 S, respectively. The corresponding calculated molecular weights were 109,000-121,000, 52,000-59,000, and 22,000-27,000. Scatchard analysis of each of these androgen receptor forms demonstrated very similar affinity for [3H]dihydrotestosterone. Extensively purified preparations of androgen receptor from R3327 tumor contained varying amounts of the three receptor forms even though molybdate and phosphocellulose were used to stabilize the androgen receptor protein during purification. It is concluded that androgen receptors from a variety of tissues share a common monomeric subunit and that stabilization is necessary during analytical and purification procedures to prevent cleavage of the monomer by endogenous proteases

  15. Preliminary investigations into triazole derived androgen receptor antagonists.

    Science.gov (United States)

    Altimari, Jarrad M; Niranjan, Birunthi; Risbridger, Gail P; Schweiker, Stephanie S; Lohning, Anna E; Henderson, Luke C

    2014-05-01

    A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated as non-steroidal androgen receptor (AR) antagonists. The motivation for this study was to replace the N-phenyl amide portion of small molecule antiandrogens with a 1,2,3-triazole and determine effects, if any, on biological activity. The synthetic methodology presented herein is robust, high yielding and extremely rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized from commercially available starting materials in less than 3h. After preliminary biological screening at 20 and 40 μM, the most promising three compounds were found to display IC50 values of 40-50 μM against androgen dependent (LNCaP) cells and serve as a starting point for further structure-activity investigations. All compounds in this work were the focus of an in silico study to dock the compounds into the human androgen receptor ligand binding domain (hARLBD) and compare their predicted binding affinity with known antiandrogens. A comparison of receptor-ligand interactions for the wild type and T877A mutant AR revealed two novel polar interactions. One with Q738 of the wild type site and the second with the mutated A877 residue.

  16. In vitro steroid-induced meiosis in Rhinella arenarum oocytes: role of pre-MPF activation.

    Science.gov (United States)

    Arias Torres, Ana Josefina; Bühler, Marta Inés; Zelarayán, Liliana Isabel

    2016-04-01

    In this work we showed the relationship between seasonal periods and the response of R. arenarum follicles and oocytes to different steroids. Using in vitro germinal vesicle breakdown (GVBD) assays, we demonstrated that P4 is the main steroid capable of inducing maturation in R. arenarum oocytes and follicles. In the second part of this work we showed that androgens can activate pre-maturation promoting factors (pre-MPFs) such as P4, by cytoplasm microinjection experiments. The results indicated that the steroids assayed induced oocyte and follicle maturation in a dose- and time-dependent manner. In oocytes, P4 was the most efficient steroid as a maturation inducer (EC50 of the reproductive period, 6 nM, EC50 of the non-reproductive period ≅ 30 nM). Androgens (DHEA, dehydroepiandrosterone; T, testosterone; and AD, androstenedione) were less efficient maturation inducers than P4 (EC50 reproductive period ≅ 50, 120 and 600 nM respectively). Similar results were obtained with intact follicles in both seasonal periods. Although the response of follicles to the different androgens was variable, in no case was it above the above the response induced by P4. Independently of the season, oocytes and follicles incubated in P4, P5 and T underwent GVBD after 6-10 h while oocytes and follicles incubated in DHEA and AD matured more slowly. Furthermore, we demonstrated that microinjection of mature cytoplasm from androgen-treated oocytes is sufficient to promote GVBD in immature recipient oocytes (DHEA, 57 ± 12%; AD, 60 ± 8%; T, 56 ± 13%). Thus, androgens such as DHEA, T and AD are as competent as P4 to activate pre-MPF. PMID:26006336

  17. Steroids (For Parents)

    Science.gov (United States)

    ... by some athletes and bodybuilders. Anabolic steroids are synthetic hormones that can boost the body's ability to ... doses every day can significantly increase levels of testosterone, which can lead to a number of health ...

  18. The CXCL12/CXCR4 axis promotes ligand-independent activation of the androgen receptor.

    Science.gov (United States)

    Kasina, Sathish; Macoska, Jill A

    2012-04-01

    The molecular mechanisms responsible for the transition of some prostate cancers from androgen ligand-dependent to androgen ligand-independent are incompletely established. Molecules that are ligands for G protein coupled receptors (GPCRs) have been implicated in ligand-independent androgen receptor (AR) activation. The purpose of this study was to examine whether CXCL12, the ligand for the GPCR, CXCR4, might mediate prostate cancer cell proliferation through AR-dependent mechanisms involving functional transactivation of the AR in the absence of androgen. The results of these studies showed that activation of the CXCL12/CXCR4 axis promoted: The nuclear accumulation of both wild-type and mutant AR in several prostate epithelial cell lines; AR-dependent proliferative responses; nuclear accumulation of the AR co-regulator SRC-1 protein; SRC-1:AR protein:protein association; co-localization of AR and SRC-1 on the promoters of AR-regulated genes; AR- and SRC-1 dependent transcription of AR-regulated genes; AR-dependent secretion of the AR-regulated PSA protein; P13K-dependent phosphorylation of AR; MAPK-dependent phosphorylation of SRC-1, and both MAPK- and P13K-dependent secretion of the PSA protein, in the absence of androgen. Taken together, these studies identify CXCL12 as a novel, non-steroidal growth factor that promotes the growth of prostate epithelial cells through AR-dependent mechanisms in the absence of steroid hormones. These findings support the development of novel therapeutics targeting the CXCL12/CXCR4 axis as an ancillary to those targeting the androgen/AR axis to effectively treat castration resistant/recurrent prostate tumors.

  19. 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.

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

    Science.gov (United States)

    Mahmoud, Abeer M; Zhu, Tian; Parray, Aijaz; Siddique, Hifzur R; Yang, Wancai; Saleem, Mohammad; Bosland, Maarten C

    2013-01-01

    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.

  1. 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

  2. Alterations in testicular histology and the mRNAs of enzymes responsible for sex steroid synthesis in the zebrafish Danio rerio exposed to nonyphenol%壬基酚对斑马鱼精巢组织及性激素合成酶基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘晓丽; 汪奇; 贾林芝; 周忠良

    2011-01-01

    壬基酚(NP)是广泛存在于水体中的环境内分泌干扰物,会影响鱼类的生殖和发育.为了解NP影响鱼类精巢发育的分子机制,将成年雄性斑马鱼(Danio rerio)暴露于不同浓度(0、125、250、500μg·L-1)NP下21d,用常规组织学方法研究试验鱼精巢组织结构的变化,并用荧光定量PCR(QRT-PCR)方法检测试验鱼精巢性激素合成酶及雌、雄激素受体(ERα、AR)基因的表达.结果表明,暴露于250μg·L-1NP的斑马鱼精巢内精子及精小囊的数目减少,非细胞区域增加;500μg·L-1NP组斑马鱼生精小管内精子凝集于管腔中央.250μg·L-1NP可导致精巢CYP17mRNA的表达量显著下调,125μg·L-1NP可导致CYP11B mRNA的表达量显著下调,并呈现出明显的负剂量-效应关系.但是,NP对精巢AR mRNA的表达无明显影响,精巢中CYP19A mRNA及ERαmRNA的表达与NP暴露浓度之间呈正剂量-效应关系,125μg·L-1NP即可显著上调CYP19A mRNA及ERαmRNA的表达.NP可通过抑制精巢中雄激素合成相关酶基因的表达影响精巢发育,同时可诱导精巢内源雌激素合成和雌激素受体的表达,提高雌激素效应.%Nonylphenol (NP),an aquatic endocrine disruptor,is known to be capable of adversely affecting fish development and reproduction.In order to elucidate the molecular mechanisms for the harmful effects of NP on testicular development in fish,the male zebrafish Danio rerio were exposed to 0,125,250 and 500 μg·L-1 NP for 21 days.Histological alterations in the testis and the mRNAs of enzymes responsible for sex steroid synthesis,estrogen receptor α (ERα) and androgen receptor (AR) were subsequently investigated.Histologically,the fish treated with 250 μg·L-1 NP exhibited reduced numbers of both spermatocyst and spermatozoan and an enlargement of acellular zone.In the fish exposed to 500 μg·L-1 NP,sperms were found to be congregated in the lumen of seminiferous tubules.Downregulation of

  3. Liquid chromatographic-mass spectrometric analysis of glucuronide-conjugated anabolic steroid metabolites: method validation and interlaboratory comparison

    NARCIS (Netherlands)

    Hintikka, L.; Kuuranne, T.; Leinonen, A.; Thevis, M.; Schanzer, W.; Halket, J.; Cowan, D.; Grosse, J.; Hemmersbach, P.; Nielen, M.W.F.; Kostiainen, R.

    2008-01-01

    Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method for simultaneous and direct detection of 12 glucuronide-conjugated anabolic androgenic steroid (AAS) metabolites in human urine is described. The compounds selected were the main metabolites detected in huma

  4. Role of androgen receptor in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    HiroyoshiSuzuki; HaruoIto

    1999-01-01

    The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80 % of prostate cancers initially respond to hormonal therapy, howcrver, more than half of the re-sponders gradtmlly become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnonnalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. "Ilais article focusedon the role of AR in the progression of prostate cancer.

  5. Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential.

    Science.gov (United States)

    Zimmer, Brenna M; Howell, Michelle E; Wei, Qin; Ma, Linlin; Romsdahl, Trevor; Loughman, Eileen G; Markham, Jonathan E; Seravalli, Javier; Barycki, Joseph J; Simpson, Melanie A

    2016-08-01

    Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD(+)-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen-dependent versus castration-resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration-resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and prostate-specific antigen (PSA) expression, as well as the androgen receptor (AR)-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration-resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression. PMID:27307252

  6. Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats.

    Science.gov (United States)

    Jahromi, Marziyeh Salehi; Tehrani, Fahimeh Ramezani; Noroozzadeh, Mahsa; Zarkesh, Maryam; Ghasemi, Asghar; Zadeh-Vakili, Azita

    2016-11-15

    It is believed that excess androgen exposure of the fetus, via altered gene expression, causes hyperandrogenism a key feature of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate expression of Cytochrome P450-17 (CYP17), GATA-binding protein (GAGT6) and Steroidogenic acute regulatory protein (StAR), genes of adult female rats prenatally exposed to androgen excess, closely reflect endocrine and ovarian disturbances of PCOS in women, by comparing them during different phases of estrus cycle with those of non-treated rats. Both the adult prenatally testosterone exposed and control rats (n=23, each) were divided into four groups based on their observed vaginal smear (proestrus, estrus, metestrus and diestrus) and the relative expression of CYP17, GATA6 and StAR genes was measured in ovarian theca cells using Cyber-green Real-Time PCR. Serum sex steroid hormones and gonadotropins levels were measured using the ELISA method; a comparison of these two groups showed that there was an overall increase in the studied genes (CYP17; 2.39 fold change, 95% CI: 1.23-3.55; P<0.05, GATA6; 2.08 fold change, 95% CI: 1.62-2.55; P<0.0001, and StAR; 1.4 fold change, 95% CI: 1.02-1.78; P<0.05), despite variations in different phases with maximum elevation for all genes in diestrus. The changes observed may impair the normal development of ovaries that mediate the programming of adult PCOS.

  7. Prenatal Androgen Excessive Exposure related to Fetal Programming of Polycystic Ovary Syndrome%宫内高雄激素环境与子代多囊卵巢综合征

    Institute of Scientific and Technical Information of China (English)

    严晓南

    2013-01-01

    近年研究认为,多囊卵巢综合征(polycystic ovary syndrome,PCOS)是一种胎源性疾病.胎儿暴露于宫内高雄激素环境,可能引起多个组织内基因表观遗传修饰状态的改变,如基因DNA甲基化、子代基因印迹的改变,干扰胎儿下丘脑-垂体-卵巢轴和内脏靶器官的生理发育过程,导致下丘脑对类固醇激素的负反馈调节敏感性下降和胰腺功能受损,造成青春期或成年后出现各种PCOS症状.明确PCOS的早期发病机制,对预防高危人群PCOS的发生与发展具有临床意义.%Clinical,experimental and genetic evidence suggested that polycystic ovary syndrome (PCOS) could have an fetal origin of adult disease.During fetal development,prenatal androgens excess may intervene the epigenome,such as the altered DNA methylation and genomic imprinting,which may increase the later risk of PCOS.Exposure to androgens in utero induces a permanent PCOS-like phenotype characterized by hyperandrogenism,abnormal follicle development,luteinizing hormone hypersecretion from the reduced hypothalamic sensitivity to steroid negative feedback,and insulin resistance from the increased abdominal adiposity.The ability of prenatal androgens excess to alter the developmental trajectory of multiple organ systems could be one of early mechanisms of PCOS pathogenesis,which could be valuable for PCOS prevention in groups with high risks.

  8. Dominant-negative androgen receptor inhibition of intracrine androgen-dependent growth of castration-recurrent prostate cancer.

    Directory of Open Access Journals (Sweden)

    Mark A Titus

    Full Text Available BACKGROUND: Prostate cancer (CaP is the second leading cause of cancer death in American men. Androgen deprivation therapy is initially effective in CaP treatment, but CaP recurs despite castrate levels of circulating androgen. Continued expression of the androgen receptor (AR and its ligands has been linked to castration-recurrent CaP growth. PRINCIPAL FINDING: In this report, the ligand-dependent dominant-negative ARΔ142-337 (ARΔTR was expressed in castration-recurrent CWR-R1 cell and tumor models to elucidate the role of AR signaling. Expression of ARΔTR decreased CWR-R1 tumor growth in the presence and absence of exogenous testosterone (T and improved survival in the presence of exogenous T. There was evidence for negative selection of ARΔTR transgene in T-treated mice. Mass spectrometry revealed castration-recurrent CaP dihydrotestosterone (DHT levels sufficient to activate AR and ARΔTR. In the absence of exogenous testosterone, CWR-R1-ARΔTR and control cells exhibited altered androgen profiles that implicated epithelial CaP cells as a source of intratumoral AR ligands. CONCLUSION: The study provides in vivo evidence that activation of AR signaling by intratumoral AR ligands is required for castration-recurrent CaP growth and that epithelial CaP cells produce sufficient active androgens for CaP recurrence during androgen deprivation therapy. Targeting intracrine T and DHT synthesis should provide a mechanism to inhibit AR and growth of castration-recurrent CaP.

  9. Steroid biosynthesis in adipose tissue.

    Science.gov (United States)

    Li, Jiehan; Papadopoulos, Vassilios; Vihma, Veera

    2015-11-01

    Tissue-specific expression of steroidogenic enzymes allows the modulation of active steroid levels in a local manner. Thus, the measurement of local steroid concentrations, rather than the circulating levels, has been recognized as a more accurate indicator of the steroid action within a specific tissue. Adipose tissue, one of the largest endocrine tissues in the human body, has been established as an important site for steroid storage and metabolism. Locally produced steroids, through the enzymatic conversion from steroid precursors delivered to adipose tissue, have been proven to either functionally regulate adipose tissue metabolism, or quantitatively contribute to the whole body's steroid levels. Most recently, it has been suggested that adipose tissue may contain the steroidogenic machinery necessary for the initiation of steroid biosynthesis de novo from cholesterol. This review summarizes the evidence indicating the presence of the entire steroidogenic apparatus in adipose tissue and discusses the potential roles of local steroid products in modulating adipose tissue activity and other metabolic parameters.

  10. Early androgen influences on human neural and behavioural development

    OpenAIRE

    Hines, Melissa

    2008-01-01

    Gonadal hormones, particularly androgens, influence sexual differentiation of the body, as well as the brain and behaviour. Ante-natal exposure to atypical hormone environments leads to alterations in human behaviours that show sex differences. These include childhood play, sexual orientation, gender identity, and personality characteristics, such as empathy and aggression. Individual variability among healthy children in antenatal hormone exposure show similar relationships to individual var...

  11. Androgens and estrogens in benign prostatic hyperplasia: past, present and future.

    Science.gov (United States)

    Nicholson, Tristan M; Ricke, William A

    2011-01-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs.

  12. Anti-androgen treatments.

    Science.gov (United States)

    Bachelot, Anne; Chabbert-Buffet, Nathalie; Salenave, Sylvie; Kerlan, Véronique; Galand-Portier, Marie-Béatrice

    2010-02-01

    1. Estrogen plus progestin contraceptives (EPP) are the first-line treatment of moderate hirsutism and acne in women of child bearing age (grade C). 2. CPA, 50mg/day, 20 days out of 28, associated with estrogen is the first-line treatment of "moderate to severe hirsutism" in women of childbearing age (grade C). 3. Spironolactone, given as a contraceptive, can be proposed as a second-line treatment in case of side effects or counter-indications to CPA in moderate to severe hirsutism (grade C) in women of childbearing age. No market authorization in this indication. 4. Flutamide or Finasteride are "only" to be used under the guise of contraception as a "thirdline therapy" in cases of severe hirsutism, the presence of side effects or counter-indications to EPP, CPA 50mg/day or spironolactone (grade C). No market authorization in this indication 5. There is no indication for GnRH analogs as an anti-androgen treatment in women of childbearing age given the current therapeutic alternatives (grade C) 6. Only long-term hair removal treatments can be proposed (grade C): electrolysis or laser hair removal. PMID:20096826

  13. ANDROGEN INSENSITIVITY SYNDROME

    Directory of Open Access Journals (Sweden)

    Kanan

    2014-01-01

    Full Text Available The condition is inherited as X - linked recessive gene 1 . The underlying pathology is the inability of end organs to respond to androgens. These cases are phenotypically and psychologically female with adequate breast development , normal external genitalia , a vagina with variable depth , absent /sparse pubic hair and axillary hair. The exact incidence in India is not known but the reported incidence is 1 in 2 , 000 to 1 in 62 ,400 worldwide . These patients have male karyotyping (XY wi th negative sex chromatin with undescended gonads. These cases are rarely diagnosed before puberty. Though rare , these are extremely distressing to the concerned individuals requiring expert handling. Management should include psychological counseling not only to determine the sexual mentation but also to help those individuals to cope with their problems. The chance of malignancy developing in the gonad with Y chromosome are about 20%.Surgical removal of the gonad is mandatory but can be delayed till 18 ye ars to permit breast development and epiphyseal closure. The aim of presenting this case is to develop awareness regarding this rare syndrome X - linked genetic disorder which runs in families

  14. 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....

  15. 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.

  16. Androgen deficiency and aging in men.

    OpenAIRE

    Swerdloff, R S; Wang, C

    1993-01-01

    Androgen levels decrease with age in men. Androgen deficiency in men older than 65 years leads to asthenia, a decrease in muscle mass, osteoporosis, and a decrease in sexual activity. Androgen deficiency has been reported to cause changes in mood and cognitive function. The combination of these factors results in impaired quality of life in older men. Androgen replacement therapy in hypogonadal men increases bone and muscle mass, enhances muscle and cardiovascular function, and improves sexua...

  17. Androgen Receptors, Sex Behaviour, and Aggression

    OpenAIRE

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

    2012-01-01

    Androgens are intricately involved in reproductive and aggressive behaviours, but the role of the androgen receptor in mediating these behaviours is less defined. Further, activity of the hypothalamic-pituitary-gonadal (HPG) axis and hypothalamic-pituitary-adrenal (HPA) axis can influence each other at the level of the androgen receptor. Knowledge of the mechanisms for androgens’ effects on behaviours through the androgen receptor will guide future studies in elucidating male reproductive and...

  18. Intra-follicular and peripheral steroid characteristics during vernal transition in the pony mare.

    Science.gov (United States)

    Davis, S D; Sharp, D C

    1991-01-01

    This experiment investigated steroid production by ovarian tissues, in vitro, of pony mares during vernal transition from anoestrus to the breeding season. Follicular dynamics were monitored to detect the first, second, third or fourth transition follicle, greater than or equal to 30 mm diameter or the first large post luteal follicle of the breeding season. Twenty-four hours after a large follicle was detected, theca (T) and granulosa (G) tissues were harvested. Separate and co-incubations of these tissues were conducted to determine steroid production in early transition (ET), late transition (LT) and pre-ovulatory (OV) follicles. Peripheral plasma and follicular fluid steroids and gonadotrophins also were assayed. Peripheral plasma oestradiol concentrations increased from ET to LT and again from LT to OV in parallel with tissue production and follicular fluid content. Androgen production increased from LT to OV whereas progesterone production showed no change, thereby indicating a possible failure of 17-alpha steroid hydroxylase in ET follicles. Examination of tissue steroid secretion rates revealed that granulosa was the major site of oestrogen production, whereas theca secreted greater amounts of androgen. PMID:1795276

  19. The in utero programming effect of increased maternal androgens and a direct fetal intervention on liver and metabolic function in adult sheep.

    Directory of Open Access Journals (Sweden)

    Kirsten Hogg

    Full Text Available Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS. We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin-like growth factor (IGF and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5 or testosterone propionate (TP; n = 9 twice weekly (100 mg; i.m from d62-102 (gestation 147 days. In a novel treatment paradigm, a second cohort received a direct C (n = 4 or TP (20 mg; n = 7 fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05 and the histological presence of fatty liver (P<0.05 independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05, glucocorticoid receptor (GR; P<0.05, UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05 and IGF1 (P<0.01 expression were upregulated. The direct fetal intervention (C and TP led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK was up-regulated in the fetal controls (P<0.05 and this was opposed by fetal TP (P<0.05. Hepatic estrogen receptor (ERα; P<0.05 and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05 were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.

  20. Developmental programming: Impact of prenatal exposure to bisphenol-A and methoxychlor on steroid feedbacks in sheep

    International Nuclear Information System (INIS)

    Bisphenol-A (BPA), a polymer used in plastics manufacturing, and methoxychlor (MXC), a pesticide, are endocrine disrupting compounds with estrogenic and anti-androgenic properties. Prenatal BPA or MXC treatment induces reproductive defects in sheep with BPA causing prepubertal luteinizing hormone (LH) hypersecretion and dampening of periovulatory LH surges and MXC lengthening follicular phase and delaying the LH surge. In this study, we addressed the underlying neuroendocrine defects by testing the following hypotheses: 1) prenatal BPA, but not MXC reduces sensitivity to estradiol and progesterone negative feedback, 2) prenatal BPA, but not MXC increases pituitary responsiveness to gonadotropin releasing hormone (GnRH), and 3) prenatal BPA dampens LH surge response to estradiol positive feedback challenge while prenatal MXC delays the timing of the LH surge. Pregnant sheep were treated with either 1) 5 mg/kg/day BPA (produces approximately twice the level found in human circulation, n = 8), 2) 5 mg/kg/day MXC (the lowest observed effect level stated in the EPA National Toxicology Program's Report; n = 6), or 3) vehicle (cotton seed oil: C: n = 6) from days 30 to 90 of gestation. Female offspring of these ewes were ovariectomized at 21 months of age and tested for progesterone negative, estradiol negative, estradiol positive feedback sensitivities and pituitary responsiveness to GnRH. Results revealed that sensitivity to all 3 feedbacks as well as pituitary responsiveness to GnRH were not altered by either of the prenatal treatments. These findings suggest that the postpubertal reproductive defects seen in these animals may have stemmed from ovarian defects and the steroidal signals emanating from them. - Highlights: ► Prenatal BPA/MXC does not affect reproductive neuroendocrine steroid feedbacks. ► Prenatal BPA or MXC treatment failed to alter pituitary sensitivity to GnRH. ► LH excess in BPA-treated sheep may be due to reduced ovarian feedback signals

  1. Developmental programming: Impact of prenatal exposure to bisphenol-A and methoxychlor on steroid feedbacks in sheep

    Energy Technology Data Exchange (ETDEWEB)

    Abi Salloum, Bachir; Steckler, Teresa L.; Herkimer, Carol; Lee, James S. [Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109 (United States); Padmanabhan, Vasantha, E-mail: vasantha@umich.edu [Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109 (United States); The Reproductive Sciences Program, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-05-01

    Bisphenol-A (BPA), a polymer used in plastics manufacturing, and methoxychlor (MXC), a pesticide, are endocrine disrupting compounds with estrogenic and anti-androgenic properties. Prenatal BPA or MXC treatment induces reproductive defects in sheep with BPA causing prepubertal luteinizing hormone (LH) hypersecretion and dampening of periovulatory LH surges and MXC lengthening follicular phase and delaying the LH surge. In this study, we addressed the underlying neuroendocrine defects by testing the following hypotheses: 1) prenatal BPA, but not MXC reduces sensitivity to estradiol and progesterone negative feedback, 2) prenatal BPA, but not MXC increases pituitary responsiveness to gonadotropin releasing hormone (GnRH), and 3) prenatal BPA dampens LH surge response to estradiol positive feedback challenge while prenatal MXC delays the timing of the LH surge. Pregnant sheep were treated with either 1) 5 mg/kg/day BPA (produces approximately twice the level found in human circulation, n = 8), 2) 5 mg/kg/day MXC (the lowest observed effect level stated in the EPA National Toxicology Program's Report; n = 6), or 3) vehicle (cotton seed oil: C: n = 6) from days 30 to 90 of gestation. Female offspring of these ewes were ovariectomized at 21 months of age and tested for progesterone negative, estradiol negative, estradiol positive feedback sensitivities and pituitary responsiveness to GnRH. Results revealed that sensitivity to all 3 feedbacks as well as pituitary responsiveness to GnRH were not altered by either of the prenatal treatments. These findings suggest that the postpubertal reproductive defects seen in these animals may have stemmed from ovarian defects and the steroidal signals emanating from them. - Highlights: ► Prenatal BPA/MXC does not affect reproductive neuroendocrine steroid feedbacks. ► Prenatal BPA or MXC treatment failed to alter pituitary sensitivity to GnRH. ► LH excess in BPA-treated sheep may be due to reduced ovarian feedback signals.

  2. Androgen deprivation therapy-associated vasomotor symptoms

    Institute of Scientific and Technical Information of China (English)

    Jason M Jones; Manish Kohli; Charles L Loprinzi

    2012-01-01

    Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer.While efficacious,ADT is associated with multiple side effects,including decreased libido,erectile dysfunction,diabetes,loss of muscle tone and altered body composition,osteoporosis,lipid changes,memory loss,gynecomastia and hot flashes.The breadth of literature for the treatment of hot flashes is much smaller in men than that in women.While hormonal therapy of hot flashes has been shown to be effective,multiple non-hormonal medications and treatment methods have also been developed.This article reviews current options for the treatment of hot flashes in patients taking ADT.

  3. Is a sex-determining gene(s) necessary for sex-determination in amphibians? Steroid hormones may be the key factor.

    Science.gov (United States)

    Nakamura, M

    2013-01-01

    Amphibians have 2 genetic sex-determining systems, one with male (XX/XY) and one with female (ZZ/ZW) heterogamety. While the ancestral state of sex-determination is thought to be female heterogamety, male and female heterogametic types were probably once interchangeable. The Japanese frog Rana rugosa has both XX/XY and ZZ/ZW systems within a single species in certain local populations. However, steroid hormones can alter the phenotypic sex epigenetically. In R. rugosa, steroidogenic enzyme expression starts before sex-determination in the indifferent gonad, and these enzymes become active in both male and female tadpoles. Androgens are produced in the indifferent gonad of male tadpoles at high levels, whereas estrogens are synthesized in females. In this regard, the observed enhanced expression of the hormone-metabolizing genes, CYP19 in the female gonad and CYP17 in males, may be crucial for sex-determination. Moreover, with FSH known to increase estrogen synthesis in the vertebrate ovary, observed upregulation of FSH receptor (FSHR) expression in the indifferent gonad of female tadpoles is intriguing. These data suggest that steroid hormones could be crucial for sex-determination in R. rugosa, with the consequence that upregulation of CYP19 and FSHR expression is necessary for female and CYP17 for male sex-determination.

  4. 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 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...... 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...

  5. Mind Over Matter: Anabolic Steroids

    Science.gov (United States)

    ... Matter Teaching Guide and Series / Anabolic Steroids Print Mind Over Matter: Anabolic Steroids Order Free Publication in: ... how drugs affect the brain and nervous system. Mind Over Matter is produced by the National Institute ...

  6. Severe Cholestasis and Bile Acid Nephropathy From Anabolic Steroids Successfully Treated With Plasmapheresis.

    Science.gov (United States)

    Flores, Avegail; Nustas, Rosemary; Nguyen, Hoang-Lan; Rahimi, Robert S

    2016-01-01

    Severe cholestasis with anabolic androgenic steroids is well-known to cause acute liver injury. Treatment is usually supportive after withdrawal of the offending agent. Acute kidney injury (AKI) frequently occurs in acute liver injury and may complicate management and prognosis. We highlight the use of plasmapheresis resulting in rapid improvement in cholestatic jaundice with resolution of AKI. Plasmapheresis should be considered in special cases in which there is progressive clinical decline despite supportive care. PMID:26958570

  7. Virilizing ovarian steroid cell tumor in a 40 year old South Indian female: a case report

    OpenAIRE

    Salim, Shihas; Shantha, Ghanshyam Palamaner Subash; Patel, Amish Dilip; Kumar, Anita A; Ganeshram, Prasanthi; Mehra, Nikita; Rajan, Anish George; Joseph, Tarun; Sudhakar, Lavangi

    2009-01-01

    Virilism is the masculinization and enhancement of male secondary sexual characteristics in females. The etiology is usually of adrenal or ovarian origin. Here we report a case of virilizing Leydig cell type, steroid cell tumor of the left ovary, in a 40 year old female who presented with clinical signs and symptoms of virilization: deepening of voice, hirsutism (Ferriman-Gallwey score 26), clitoromegaly, and androgenic alopecia. On further evaluation, laboratory investigations revealed hyper...

  8. High-Mobility Group Chromatin Proteins 1 and 2 Functionally Interact with Steroid Hormone Receptors To Enhance Their DNA Binding In Vitro and Transcriptional Activity in Mammalian Cells

    OpenAIRE

    Boonyaratanakornkit, Viroj; Melvin, Vida; Prendergast, Paul; Altmann, Magda; Ronfani, Lorenza; Marco E. Bianchi; Taraseviciene, Laima; Nordeen, Steven K.; Allegretto, Elizabeth A.; Edwards, Dean P.

    1998-01-01

    We previously reported that the chromatin high-mobility group protein 1 (HMG-1) enhances the sequence-specific DNA binding activity of progesterone receptor (PR) in vitro, thus providing the first evidence that HMG-1 may have a coregulatory role in steroid receptor-mediated gene transcription. Here we show that HMG-1 and the highly related HMG-2 stimulate DNA binding by other steroid receptors, including estrogen, androgen, and glucocorticoid receptors, but have no effect on DNA binding by se...

  9. A Novel Mutation in the CYP11B1 Gene Causes Steroid 11β-Hydroxylase Deficient Congenital Adrenal Hyperplasia with Reversible Cardiomyopathy

    OpenAIRE

    Alqahtani, Mohammad A.; Ayed A. Shati; Minjing Zou; Alsuheel, Ali M.; Alhayani, Abdullah A.; Al-Qahtani, Saleh M.; Gilban, Hessa M.; Meyer, Brain F.; Yufei Shi

    2015-01-01

    Congenital adrenal hyperplasia (CAH) due to steroid 11β-hydroxylase deficiency is the second most common form of CAH, resulting from a mutation in the CYP11B1 gene. Steroid 11β-hydroxylase deficiency results in excessive mineralcorticoids and androgen production leading to hypertension, precocious puberty with acne, enlarged penis, and hyperpigmentation of scrotum of genetically male infants. In the present study, we reported 3 male cases from a Saudi family who presented with penile enlargem...

  10. 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)

    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.

  11. Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential

    Science.gov (United States)

    Zimmer, Brenna M.; Howell, Michelle E.; Wei, Qin; Ma, Linlin; Romsdahl, Trevor; Loughman, Eileen G.; Markham, Jonathan E.; Seravalli, Javier; Barycki, Joseph J.; Simpson, Melanie A.

    2016-01-01

    Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and PSA expression, as well as the AR-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch 1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression. PMID:27307252

  12. Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.

    Science.gov (United States)

    Brooke, Greg N; Gamble, Simon C; Hough, Michael A; Begum, Shajna; Dart, D Alwyn; Odontiadis, Michael; Powell, Sue M; Fioretti, Flavia M; Bryan, Rosie A; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L

    2015-05-01

    Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic

  13. High abundance androgen receptor in goldfish brain: characteristics and seasonal changes

    International Nuclear Information System (INIS)

    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 [3H]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

  14. Steroids. A Resource Guide.

    Science.gov (United States)

    New York State Education Dept., Albany. Bureau of School Health Education and Services.

    This guide provides information on steroid use as well as prevention and intervention strategies. It is intended to serve as a supplement to drug abuse education and prevention programs in elementary and secondary schools and as the basis for local curriculum development and instructional activities. The following topics are covered: (1) history…

  15. 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

  16. Laparoscopic gonedectomy in a case of complete androgen insensitivity syndrome

    OpenAIRE

    Bhaskararao, G.; Himabindu, Y.; Samir Ranjan Nayak; Sriharibabu, M.

    2014-01-01

    Complete Androgen insensitivity syndrome is a disorder of hormone resistance characterized by a female phenotype in an individual with an XY karyotype. The pathogenesis of CAIS involves a defective androgen receptor gene located on X-chromosome at Xq11-12and end organ insensitivity to androgens, although androgen concentrations are appropriate for the age of the patient. There are three major types of androgen insensitivity syndrome: Complete androgen insensitivity syndrome, minimal androgen ...

  17. Androgen-Responsive MicroRNAs in Mouse Sertoli Cells

    OpenAIRE

    Subbarayalu Panneerdoss; Yao-Fu Chang; Kalyan C Buddavarapu; Hung-I Harry Chen; Gunapala Shetty; Huizhen Wang; Yidong Chen; T Rajendra Kumar; Rao, Manjeet K.

    2012-01-01

    Although decades of research have established that androgen is essential for spermatogenesis, androgen's mechanism of action remains elusive. This is in part because only a few androgen-responsive genes have been definitively identified in the testis. Here, we propose that microRNAs – small, non-coding RNAs – are one class of androgen-regulated trans-acting factors in the testis. Specifically, by using androgen suppression and androgen replacement in mice, we show that androgen regulates the ...

  18. 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…

  19. Synthesis of Steroidal Thiadiazoles from Steroidal Ketones

    Directory of Open Access Journals (Sweden)

    M. Akhtar

    2005-08-01

    Full Text Available Syntheses of steroidal heterocycles containing a five-membered N,S- heterocycle attached at the 6,7 positions of the B ring are reported. 5α-Cholestane-6-one (1, its 3β-acetoxy- (2 and 3β-chloro- (3 analogues reacted with semicarbazide and aqueous sodium acetate in refluxing ethanol to yield 5α-cholestan-6-one-semicarbazone 1a and its 3-β-acetoxy and 3β-chloro derivatives 2a and 3a, respectively. The reactions of 1a, 2a and 3a with thionyl chloride in dichloromethane at low temperature afforded the cyclized thiadiazole 4 and its 3β-acetoxy- and 3β-chloro analogues 5 and 6 in good yields.

  20. β-Catenin Binds to the Activation Function 2 Region of the Androgen Receptor and Modulates the Effects of the N-Terminal Domain and TIF2 on Ligand-Dependent Transcription

    OpenAIRE

    Song, Liang-Nian; Herrell, Roger; Byers, Stephen; Shah, Salimuddin; Wilson, Elizabeth M.; Gelmann, Edward P.

    2003-01-01

    β-Catenin is a multifunctional molecule that is activated by signaling through WNT receptors. β-Catenin can also enhance the transcriptional activity of some steroid hormone receptors such as the androgen receptor and retinoic acid receptor α. Androgens can affect nuclear translocation of β-catenin and influence its subcellular distribution. Using mammalian two-hybrid binding assays, analysis of reporter gene transcription, and coimmunoprecipitation, we now show that β-catenin binds to the an...

  1. Discovery of the selective androgen receptor modulator MK-0773 using a rational development strategy based on differential transcriptional requirements for androgenic anabolism versus reproductive physiology.

    Science.gov (United States)

    Schmidt, Azriel; Kimmel, Donald B; Bai, Chang; Scafonas, Angela; Rutledge, Sujane; Vogel, Robert L; McElwee-Witmer, Sheila; Chen, Fang; Nantermet, Pascale V; Kasparcova, Viera; Leu, Chih-Tai; Zhang, Hai-Zhuan; Duggan, Mark E; Gentile, Michael A; Hodor, Paul; Pennypacker, Brenda; Masarachia, Patricia; Opas, Evan E; Adamski, Sharon A; Cusick, Tara E; Wang, Jiabing; Mitchell, Helen J; Kim, Yuntae; Prueksaritanont, Thomayant; Perkins, James J; Meissner, Robert S; Hartman, George D; Freedman, Leonard P; Harada, Shun-ichi; Ray, William J

    2010-05-28

    Selective androgen receptor modulators (SARMs) are androgen receptor (AR) ligands that induce anabolism while having reduced effects in reproductive tissues. In various experimental contexts SARMs fully activate, partially activate, or even antagonize the AR, but how these complex activities translate into tissue selectivity is not known. Here, we probed receptor function using >1000 synthetic AR ligands. These compounds produced a spectrum of activities in each assay ranging from 0 to 100% of maximal response. By testing different classes of compounds in ovariectomized rats, we established that ligands that transactivated a model promoter 40-80% of an agonist, recruited the coactivator GRIP-1 MK-0773, a 4-aza-steroid that exhibited tissue selectivity in humans. Thus, AR activated to moderate levels due to reduced cofactor recruitment, and N-/C-terminal interactions produce a fully anabolic response, whereas more complete receptor activation is required for reproductive effects. This bimodal activation provides a molecular basis for the development of SARMs. PMID:20356837

  2. Discovery of the Selective Androgen Receptor Modulator MK-0773 Using a Rational Development Strategy Based on Differential Transcriptional Requirements for Androgenic Anabolism Versus Reproductive Physiology*

    Science.gov (United States)

    Schmidt, Azriel; Kimmel, Donald B.; Bai, Chang; Scafonas, Angela; Rutledge, SuJane; Vogel, Robert L.; McElwee-Witmer, Sheila; Chen, Fang; Nantermet, Pascale V.; Kasparcova, Viera; Leu, Chih-tai; Zhang, Hai-Zhuan; Duggan, Mark E.; Gentile, Michael A.; Hodor, Paul; Pennypacker, Brenda; Masarachia, Patricia; Opas, Evan E.; Adamski, Sharon A.; Cusick, Tara E.; Wang, Jiabing; Mitchell, Helen J.; Kim, Yuntae; Prueksaritanont, Thomayant; Perkins, James J.; Meissner, Robert S.; Hartman, George D.; Freedman, Leonard P.; Harada, Shun-ichi; Ray, William J.

    2010-01-01

    Selective androgen receptor modulators (SARMs) are androgen receptor (AR) ligands that induce anabolism while having reduced effects in reproductive tissues. In various experimental contexts SARMs fully activate, partially activate, or even antagonize the AR, but how these complex activities translate into tissue selectivity is not known. Here, we probed receptor function using >1000 synthetic AR ligands. These compounds produced a spectrum of activities in each assay ranging from 0 to 100% of maximal response. By testing different classes of compounds in ovariectomized rats, we established that ligands that transactivated a model promoter 40–80% of an agonist, recruited the coactivator GRIP-1 MK-0773, a 4-aza-steroid that exhibited tissue selectivity in humans. Thus, AR activated to moderate levels due to reduced cofactor recruitment, and N-/C-terminal interactions produce a fully anabolic response, whereas more complete receptor activation is required for reproductive effects. This bimodal activation provides a molecular basis for the development of SARMs. PMID:20356837

  3. Targeting intratumoral androgens: statins and beyond.

    Science.gov (United States)

    Schweizer, Michael T; Yu, Evan Y

    2016-09-01

    While initially effective, androgen deprivation therapy (ADT) is not curative, and nearly all men with advanced prostate cancer will eventually progress to the more resistant, and ultimately lethal form of the disease, so called castration-resistant prostate cancer (CRPC). The maintenance of androgens within the prostate cancer microenvironment likely represents one of the key mechanisms by which this transition from hormone-sensitive to CRPC occurs. This can be accomplished either through intratumoral androgen biosynthesis or the active transport of androgens and androgenic precursors into the tumor microenvironment. More recently, preclinical and clinical data supported therapeutic strategies that seek to target these two mechanisms, either through the use of drugs that impair androgen biosynthesis (e.g. inhibiting the steroidogenic enzymes CYP17 and AKR1C3 with abiraterone and indomethacin, respectively) or drugs that inhibit the SLCO transporters responsible for importing androgens (e.g. statins). PMID:27583031

  4. Anogenital distance as a marker of androgen exposure in humans.

    Science.gov (United States)

    Thankamony, A; Pasterski, V; Ong, K K; Acerini, C L; Hughes, I A

    2016-07-01

    Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a 'testicular dysgenesis syndrome'. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance (AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well-defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate

  5. Analytical approach for the determination of steroid profile of humans by gas chromatography isotope ratio mass spectrometry aimed at distinguishing between endogenous and exogenous steroids.

    Science.gov (United States)

    Bulska, Ewa; Gorczyca, Damian; Zalewska, Izabela; Pokrywka, Andrzej; Kwiatkowska, Dorota

    2015-03-15

    The contamination of commonly used supplements by unknown steroids as well as their metabolites (parent compounds) become a challenge for the analytical laboratories. Although the determination of steroids profile is not trivial because of the complex matrix and low concentration of single compound, one of the most difficult current problem is to distinguish, during analytical procedure, endogenous androgens such as testosterone, dehydrotestosterone or dehydroepiandrosterone from their synthetic equivalents. The aim of this work was to develop and validate an analytical procedure for determination of the steroid profile in human urine by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) toward distinguishing between endogenous and exogenous steroids. Beside the optimization of the experimental parameters for gas chromatography separation and mass spectrometry, attention was focused on urine sample preparation. Using an optimized sample preparation protocol it was possible to achieve better chromatographic resolutions and better sensitivity enabling the determination of 5 steroids, androsterone, etiocholanolone, testosterone, 5-androstandiol, 11-hydroxyandrdostane, pregnandiol, with the expanded uncertainty (k=2) below 1‰. This enable to evaluate the significant shift of the δ(13)C/(12)C [‰] values for each of examined steroids (excluding ERC). The analytical protocol described in this work was successfully used for the confirmation of positive founding urine by evaluation T/E ratio after GC/C/IRMS analysis. PMID:25498150

  6. 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...

  7. 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)

    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.)

  8. Steroid Use in Sepsis

    Directory of Open Access Journals (Sweden)

    Şerife Mehlika Kuşkonmaz

    2013-12-01

    Full Text Available Sepsis is defined as “systemic signs and symptoms of infection in the presence of infection”. Nearly one fourth of sepsis cases eventually die. Therefore, rapid and correct management of sepsis is important. There is no reliable test to evaluate adrenal insufficiency in sepsis due to the changes in the hypothalamic-pituitary-adrenal axis and intracellular effects of cortisol during the critical illness. Clinical studies reported conflicting results regarding the effects of steroid therapy on mortality and morbidity in sepsis. Contemporary sepsis management guidelines - although not based on strong evidence - suggest consideration of steroid use in septic patients who do not respond to intravenous fluids and vasopressors. Stronger evidence obtained from randomized controlled trials is needed for this suggestion to be certain. Turk Jem 2013; 17: 121-4

  9. 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.

  10. Steroid resistance in leukemia

    OpenAIRE

    Shah, Darshan S; Kumar, Raj

    2013-01-01

    There are several types of leukemia which are characterized by the abnormal growth of cells from the myeloid or lymphoid lineage. Because of their lympholytic actions, glucocorticoids (GCs) are included in many therapeutic regimens for the treatment of various forms of leukemia. Although a significant number of acute lymphoblastic leukemia patients respond well to GC treatment during initial phases; prolonged treatments sometimes results in steroid-resistance. The exact mechanism of this resi...

  11. Steroids facing emotions

    OpenAIRE

    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 are pictures of human facial expressions of emotion. The main interest was in establishing psychoneuronedocrine and psychological motivational predictors of biased processing of angry and fearful f...

  12. A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus.

    Science.gov (United States)

    Simitsidellis, Ioannis; Gibson, Douglas A; Cousins, Fiona L; Esnal-Zufiaurre, Arantza; Saunders, Philippa T K

    2016-05-01

    The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women. PMID:26963473

  13. Modelling the interaction of steroid receptors with endocrine disrupting chemicals

    Directory of Open Access Journals (Sweden)

    Milanesi Luciano

    2005-12-01

    Full Text Available Abstract Background The organic polychlorinated compounds like dichlorodiphenyltrichloroethane with its metabolites and polychlorinated biphenyls are a class of highly persistent environmental contaminants. They have been recognized to have detrimental health effects both on wildlife and humans acting as endocrine disrupters due to their ability of mimicking the action of the steroid hormones, and thus interfering with hormone response. There are several experimental evidences that they bind and activate human steroid receptors. However, despite the growing concern about the toxicological activity of endocrine disrupters, molecular data of the interaction of these compounds with biological targets are still lacking. Results We have used a flexible docking approach to characterize the molecular interaction of seven endocrine disrupting chemicals with estrogen, progesterone and androgen receptors in the ligand-binding domain. All ligands docked in the buried hydrophobic cavity corresponding to the hormone steroid pocket. The interaction was characterized by multiple hydrophobic contacts involving a different number of residues facing the binding pocket, depending on ligands orientation. The EDC ligands did not display a unique binding mode, probably due to their lipophilicity and flexibility, which conferred them a great adaptability into the hydrophobic and large binding pocket of steroid receptors. Conclusion Our results are in agreement with toxicological data on binding and allow to describe a pattern of interactions for a group of ECD to steroid receptors suggesting the requirement of a hydrophobic cavity to accommodate these chlorine carrying compounds. Although the affinity is lower than for hormones, their action can be brought about by a possible synergistic effect.

  14. Reproductive steroid receptors and actions in the locus coeruleus of male macaques: Part of an aggression circuit?

    Science.gov (United States)

    Bethea, Cynthia L; Belikova, Yelena; Phu, Kenny; Mammerella, Grace

    2016-11-01

    This study was initiated to determine whether the noradrenergic (NE) neurons of the locus coeruleus (LC) could mediate the stimulatory action of androgens on serotonin-related gene expression in male macaques. These experiments follow our observations that serotonin neurons lack androgen receptors (ARs), and yet respond to androgens. Male Japanese macaques (Macaca fuscata) were castrated for 5-7months and then treated for 3months with [1] placebo, [2] T (testosterone), [3] DHT (dihydrotestosterone; non-aromatizable androgen) plus ATD (steroidal aromatase inhibitor), or [4] FLUT (Flutamide; androgen antagonist) plus ATD (n=5/group). The noradrenergic (NE) innervation of the raphe was determined with immunolabeling of axons with an antibody to dopamine-β-hydroxylase (DBH). Immunolabeling of tyrosine hydroxylase (TH) dendrites and corticotropin releasing hormone (CRH) axons innervating the LC was also determined. Due to the longer treatment period employed, the expression of the cognate nuclear receptors was sought. Androgen receptor (AR), estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) immunostaining was accomplished. Quantitative image analysis was applied and immunopositive neurons or axons with boutons were measured. Double-label of NE neurons for each receptor plus TH determined whether the receptors were localized in NE neurons. Androgens with or without aromatase activity significantly stimulated DBH axon density in the raphe (ANOVA, p=0.006), and LC dendritic TH (ANOVA, p80% of LC NE neurons contained ERα or ERβ. In conclusion, the LC NE neurons may transduce the stimulatory effect of androgens on serotonin-related gene expression. Since LC NE neurons lack AR, the androgenic stimulation of dendritic TH and axonal DBH may be indirectly mediated by other neurons. Estrogen, either from metabolism of T or from de novo synthesis, appears necessary for robust CRH innervation of the LC, which differs from female macaques. PMID:27083854

  15. School Sports and Adolescent Steroid Use: National Trends and Race-Ethnic Variations

    Science.gov (United States)

    Hua, Lv; Braddock, Jomills Henry, II

    2008-01-01

    In the United States, it has been reported that 4% to 12% of male adolescents and 0.5% to 2.9% of female adolescents have used anabolic steroids to enhance sports performance or favorably alter body size. Although medical, legal, and ethical issues related to the nonmedical use of anabolic steroids have been widely publicized, a growing number of…

  16. 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…

  17. Oncogenic herpesvirus HHV-8 promotes androgen-independent prostate cancer growth.

    Science.gov (United States)

    Mygatt, Justin G; Singhal, Adit; Sukumar, Gauthaman; Dalgard, Clifton L; Kaleeba, Johnan A R

    2013-09-15

    Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)-mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer. PMID:24005834

  18. Steroid signaling activation and intracellular localization of sex steroid receptors

    OpenAIRE

    Giraldi, Tiziana; Giovannelli, Pia; Di Donato, Marzia; Castoria, Gabriella; Migliaccio, Antimo; Auricchio, Ferdinando

    2010-01-01

    In addition to stimulating gene transcription, sex steroids trigger rapid, non-genomic responses in the extra-nuclear compartment of target cells. These events take place within seconds or minutes after hormone administration and do not require transcriptional activity of sex steroid receptors. Depending on cell systems, activation of extra-nuclear signaling pathways by sex steroids fosters cell cycle progression, prevents apoptosis, leads to epigenetic modifications and increases cell migrat...

  19. The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens.

    Science.gov (United States)

    Rendon, Nikki M; Rudolph, Lauren M; Sengelaub, Dale R; Demas, Gregory E

    2015-11-22

    Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short 'winter-like' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a 'seasonal switch' from gonadal to adrenal regulation of aggression by direct action on the adrenal glands.

  20. 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.

  1. Androgen Receptor in Macrophages of Male Rat is Greater Than in Female

    Directory of Open Access Journals (Sweden)

    Kazem Ahmadi

    2005-01-01

    Full Text Available he presence and possible sex differences of androgen receptor in peritoneal macrophages was investigated using immunomagnetic beads. Macrophages were incubated with different concentrations of [3H]-5αDHT in the presence or absence of a 100 fold excess of unlabelled 5α-DHT. Labelled cells were separated from unbound steroid by immunomagnetic beads coated with anti-rat macrophage antibody. The binding identified in the rat macrophages was highly selective towards androgenic compounds. The dissociation constant (kd value for the receptor was calculated to be 3.3X10-9M and 5X10-9M for macrophages of male and female rat respectively. The number of receptors in each cell was 792±3 and 120±1 for male and female respectively. Indicating a sex differences in androgen receptor (p<0.001. Taken together it can be concluded that part of sex differences in immune responses and also auto-immune disease could be related to sex differences in androgen receptor in macrophages.

  2. Cloning and expression analysis of androgen receptor gene in chicken embryogenesis.

    Science.gov (United States)

    Katoh, Hironori; Ogino, Yukiko; Yamada, Gen

    2006-03-01

    We cloned a full-length androgen receptor (AR) cDNA from chicken (Gallus gallus) gonads. The cDNA sequence has an open reading frame of 2109 bp encoding 703 amino acids. The chicken AR (cAR) shares high homology with ARs from other species in its amino acid sequences, in particular DNA binding domain (DBD) and ligand binding domain (LBD). RT-PCR analysis revealed that cAR mRNA is expressed in several embryonic tissues of both sexes, and relatively higher expression was observed in left ovary compared with testis. The immunoreactive signal of AR was co-localized within the ovarian cell nucleus, while such nuclear localization was not detected in those of testis. To get insight on the possible role of androgen-AR signaling during gonadal development, non-steroidal AR antagonist, flutamide, was administrated in ovo. The treatment induced the disorganization of sex cords in ovarian cortex at day 12 of incubation. The effect was restored by testosterone co-treatment, implying the possibility that AR mediated signaling may be involved in ovarian morphogenesis. Furthermore, co-treatment of flutamide with estradiol-17beta (E2) also restored the phenotype, suggesting androgen-AR signaling might activate aromatase expression that is necessary for estrogen synthesis. These findings suggest androgen-AR signaling might contribute to chicken embryonic ovarian development. PMID:16480982

  3. Androgen Deprivation-Induced Senescence Promotes Outgrowth of Androgen-Refractory Prostate Cancer Cells

    OpenAIRE

    Burton, Dominick G. A.; Giribaldi, Maria G.; Anisleidys Munoz; Katherine Halvorsen; Asmita Patel; Merce Jorda; Carlos Perez-Stable; Priyamvada Rai

    2013-01-01

    Androgen deprivation (AD) is an effective method for initially suppressing prostate cancer (PC) progression. However, androgen-refractory PC cells inevitably emerge from the androgen-responsive tumor, leading to incurable disease. Recent studies have shown AD induces cellular senescence, a phenomenon that is cell-autonomously tumor-suppressive but which confers tumor-promoting adaptations that can facilitate the advent of senescence-resistant malignant cell populations. Because androgen-refra...

  4. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion

    OpenAIRE

    Harris, William P.; Mostaghel, Elahe A.; Peter S Nelson; Montgomery, Bruce

    2009-01-01

    Androgen deprivation therapy remains a critical component of treatment for men with advanced prostate cancer, and data supports its use in metastatic disease and in conjunction with surgery or radiation in specific settings. Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit. Current androgen deprivation strategies seem to incompletely suppress...

  5. A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells

    OpenAIRE

    Li, Tzu-Huey; Zhao, Hongjuan; Peng, Yue; Beliakoff, Jason; James D Brooks; Sun, Zijie

    2007-01-01

    Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive...

  6. Human androgen deficiency: insights gained from androgen receptor knockout mouse models

    OpenAIRE

    Kesha Rana; Davey, Rachel A; Zajac, Jeffrey D

    2014-01-01

    The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor (AR) through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout (ARKO) models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immu...

  7. Genotype versus phenotype in families with androgen insensitivity syndrome

    NARCIS (Netherlands)

    Boehmer, ALM; Bruggenwirth, H; Van Assendelft, C; Otten, BJ; Verleun-Mooijman, MCT; Niermeijer, MF; Brunner, HG; Rouwe, CW; Waelkens, JJ; Oostdijk, W; Kleijer, WJ; Van der Kwast, TH; De Vroede, MA; Drop, SLS

    2001-01-01

    Androgen insensitivity syndrome encompasses a wide range of phenotypes, which are caused by numerous different mutations in the AR gene. Detailed information on the genotype/ phenotype relationship in androgen insensitivity syndrome is important for sex assignment, treatment of androgen insensitivit

  8. The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.

    Science.gov (United States)

    Capper, Cameron P; Rae, James M; Auchus, Richard J

    2016-06-01

    Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research. PMID:26969590

  9. Steroid Cell Tumor of the Ovary in an Adolescent: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Gokhan Boyraz

    2013-01-01

    Full Text Available Steroid cell tumors (SCTs of the ovary are a rare subgroup of sex cord tumors, account for less than 0.1% of all ovarian tumors, and also will present at any age. These tumors can produce steroids, especially testosterone, and may give symptoms like hirsutism, hair loss, amenorrhea, or oligomenorrhea. For the evaluation of androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S are the first laboratory tests to be measured. A pelvic ultrasound and a magnetic resonance imaging are useful radiologic imaging techniques. Although steroid cell tumors are generally benign, there is a risk of malignant transformation and clinical malignant formation. Surgery is the most important and hallmark treatment.

  10. Transsynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity

    Science.gov (United States)

    Brenowitz, Eliot A.

    2014-01-01

    The avian song control system provides an excellent model for studying transsynaptic trophic effects of steroid sex hormones. Seasonal changes in systemic testosterone (T) and its metabolites regulate plasticity of this system. Steroids interact with the neurotrophin brain-derived neurotrophic factor (BDNF) to influence cellular processes of plasticity in nucleus HVC of adult birds, including the addition of newborn neurons. This interaction may also occur transsynpatically; T increases the synthesis of BDNF in HVC, and BDNF protein is then released by HVC neurons on to postsynaptic cells in nucleus RA where it has trophic effects on activity and morphology. Androgen action on RA neurons increases their activity and this has a retrograde trophic effect on the addition of new neurons to HVC. The functional linkage of sex steroids to BDNF may be of adaptive value in regulating the trophic effects of the neurotrophin and coordinating circuit function in reproductively relevant contexts. PMID:25285401

  11. Multiple steroid radioimmunoassays and automation. Versatile techniques for reproductive endocrinology

    International Nuclear Information System (INIS)

    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)

  12. Impaired Physical Performance and Clinical Responses after a Recreational Bodybuilder's Self-Administration of Steroids: A Case Report.

    Science.gov (United States)

    Veras, Katherine; Silva-Junior, Fernando Lopes; Lima-Silva, Adriano Eduardo; De-Oliveira, Fernando Roberto; Pires, Flávio Oliveira

    2015-12-01

    We reported clinical and physical responses to 7 weeks of anabolic-androgenic steroid (AAS) self-administration in a male recreational bodybuilder. He was self-administrating a total of 3,250 mg of testosterone when his previous and current clinical and physical trials records were revisited. Body shape, performance, and biochemistry results were clustered into three phases labeled PRE (before the self-use), POST I (immediately at the cessation of the 7-week administration), and POST II (12 weeks after the cessation). Elevated testosterone and estradiol levels were observed in the POST I phase, while hepatic and renal functions remained altered in the POST II phase. Body mass and body fat percentages increased throughout the three phases. When adjusted according to body mass, drops in aerobic and anaerobic power and capacity (2.1% to 12.9%) were observed across the phases. This case report shows that overall performance decreased when a bodybuilding practitioner self-administered AAS. PMID:26770942

  13. The effect of anabolic steroids on the gastrointestinal system, kidneys, and adrenal glands.

    Science.gov (United States)

    Modlinski, Ryan; Fields, Karl B

    2006-04-01

    Over the past several decades we have seen an increase in the prevalence of anabolic steroid use by athletes. Because use of anabolic steroids is illicit, much of our knowledge of their side effects is derived from case reports, retrospective studies, or comparisons with studies in other similar patient groups. It has been shown that high-dose anabolic steroids have an effect on lowering high-density lipoprotein, increasing low-density lipoprotein, and increasing the atherogenic-promoting apolipoprotein A. Steroid abuse can also be hepatotoxic, promoting disturbances such as biliary stasis, peliosis hepatis, and even hepatomas, which are all usually reversible upon discontinuation. Suppression of the hypothalamic adrenal axis can also lead to profound adrenal changes that are also reversible with time. Although rare, renal side effects have also been documented, leading to acute renal failure and even Wilms' tumors in isolated cases. Much of our knowledge of these potentially severe but usually limited side effects is confounded by use of combinations of different steroid preparations and by the concomitant use with other substances. Physicians must target their efforts at counseling adolescents and other athletes about the potential harms of androgenic anabolic steroids and the legal options to improve strength and performance.

  14. Androgens and erythropoiesis: past and present.

    Science.gov (United States)

    Shahani, S; Braga-Basaria, M; Maggio, M; Basaria, S

    2009-09-01

    Association between androgens and erythropoiesis has been known for more than seven decades. Androgens stimulate hematopoietic system by various mechanisms. These include stimulation of erythropoietin release, increasing bone marrow activity and iron incorporation into the red cells. Before the discovery of recombinant erythropoietin (rhEpo), androgens were used in the treatment of anemia associated with renal disease, bone marrow suppression, and hypopituitarism. Anabolism is an additional advantage of androgen therapy. Furthermore, in light of recent reports regarding adverse effects of rhEpo, the role of androgen therapy in various types of anemias should be readdressed. Polycythemia remains a known side effect of androgen therapy. In this review, we will briefly discuss the initial animal and human studies which demonstrated the role of androgens in the treatment of anemia, their mechanism of action, a detailed account of the efficacy of androgens in the treatment of various anemias, the erythropoietic side effects of androgens and finally, the relationship between hematocrit levels and cardiovascular disease. PMID:19494706

  15. Structural basis for androgen specificity and oestrogen synthesis in human aromatase

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Debashis; Griswold, Jennifer; Erman, Mary; Pangborn, Walter; (HWMRI)

    2009-03-06

    Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens. Aromatase inhibitors therefore constitute a frontline therapy for oestrogen-dependent breast cancer. In a three-step process, each step requiring 1 mol of O{sub 2}, 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16{alpha}-hydroxytestosterone to oestrone, 17{beta}-oestradiol and 17{beta},16{alpha}-oestriol, respectively. The first two steps are C19-methyl hydroxylation steps, and the third involves the aromatization of the steroid A-ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full-length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme's androgenic specificity and unique catalytic mechanism can be used for developing next-generation aromatase inhibitors.

  16. Prolonged androgen deprivation leads to downregulation of androgen receptor and prostate-specific membrane antigen in prostate cancer cells

    OpenAIRE

    Liu, Tiancheng; Wu, Lisa Y.; Fulton, Melody D.; JOHNSON, JACQUELINE M.; Berkman, Clifford E.

    2012-01-01

    Emergence of androgen-independent cancer cells during androgen deprivation therapy presents a significant challenge to successful treatment outcomes in prostate cancer. Elucidating the role of androgen deprivation in the transition from an androgen-dependent to an androgen-independent state may enable the development of more effective therapeutic strategies against prostate cancer. Herein, we describe an in vitro model for assessing the effects of continuous androgen-deprivation on prostate c...

  17. Neuroactive steroids and their role in epilepsy

    Directory of Open Access Journals (Sweden)

    Chetan Y. Patil

    2012-06-01

    Full Text Available Neuroactive steroids are the certain steroids that alter neuronal excitability via the cell surface through interaction with certain neurotransmitter receptors. Neuroactive steroids regulate physiological functions of the central nervous system and have possible therapeutic potential in neurological diseases. They have been shown to affect neuronal excitability via their interaction with the ligand-gated ion channel family, such as the GABAA receptor by acting genomically as well as nongenomically. Positive modulators of GABAA receptor have anticonvulsant action as they enhance GABAergic transmission thereby increasing the seizure threshold. By virtue of these properties, neurosteroids appear to be relevant to pathophysiology and pharmacological treatment of many neurological diseases including catamenial epilepsy, stress induced epilepsy, temporal lobe epilepsy, alcohol withdrawal seizures, infantile spasm and status epilepticus. So far, only synthetic neurosteroid, ganaxolone has been tried in treatment of epilepsy and has shown good efficacy and tolerability. But, human data of trials are limited and hence, large double-blinded, placebo-controlled, randomized clinical trials are required before their use. The paper reviews the biosynthesis and GABAA receptor modulation of neurosteroids and their potential role in epilepsy. [Int J Basic Clin Pharmacol 2012; 1(3.000: 150-159

  18. The role of androgens and polymorphisms in the androgen receptor in the epidemiology of breast cancer

    International Nuclear Information System (INIS)

    Testosterone binds to the androgen receptor in target tissue to mediate its effects. Variations in testosterone levels and androgen receptor activity may play a role in the etiology of breast cancer. Here, we review the epidemiologic evidence linking endogenous testosterone to breast cancer risk. Paradoxically, results from observational studies that have examined polymorphisms in the androgen receptor suggest that the low-activity androgen receptor increases breast cancer risk. We review the quality of this evidence and conclude with a discussion of how the androgen receptor and testosterone results coincide

  19. Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis.

    Science.gov (United States)

    Handa, R J; Burgess, L H; Kerr, J E; O'Keefe, J A

    1994-12-01

    The rapid activation of stress-responsive neuroendocrine systems is a basic reaction of animals to perturbations in their environment. One well-established response is that of the hypothalamo-pituitary-adrenal (HPA) axis. In rats, corticosterone is the major adrenal steroid secreted and is released in direct response to adrenocorticotropin (ACTH) secreted from the anterior pituitary gland. ACTH in turn is regulated by the hypothalamic factor, corticotropin-releasing hormone. A sex difference exists in the response of the HPA axis to stress, with females reacting more robustly than males. It has been demonstrated that in both sexes, products of the HPA axis inhibit reproductive function. Conversely, the sex differences in HPA function are in part due to differences in the circulating gonadal steroid hormone milieu. It appears that testosterone can act to inhibit HPA function, whereas estrogen can enhance HPA function. One mechanism by which androgens and estrogens modulate stress responses is through the binding to their cognate receptors in the central nervous system. The distribution and regulation of androgen and estrogen receptors within the CNS suggest possible sites and mechanisms by which gonadal steroid hormones can influence stress responses. In the case of androgens, data suggest that the control of the hypothalamic paraventricular nucleus is mediated trans-synaptically. For estrogen, modulation of the HPA axis may be due to changes in glucocorticoid receptor-mediated negative feedback mechanisms. The results of a variety of studies suggest that gonadal steroid hormones, particularly testosterone, modulate HPA activity in an attempt to prevent the deleterious effects of HPA activation on reproductive function. PMID:7729815

  20. 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

  1. Teens and Steroids: A Dangerous Combo

    Science.gov (United States)

    ... warns teens and parents about the dangers of steroid use. Q: What are anabolic steroids and how many ... but the truth is that the frequency of steroid use in this age group is far greater than ...

  2. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    OpenAIRE

    MOMOZONO, HIROYUKI; Miyake, Hideaki; TEI, HIROMOTO; Harada, Ken-ichi; Fujisawa, Masato

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With...

  3. Role of Steroids in COPD

    OpenAIRE

    Vishnu Sharma

    2002-01-01

    There has been a lot of debate regarding the role of steroids in the management of Chronic Obstructive Pulmonary Disease. Now with a better understanding of the pathophysiology of COPD, the role of steroids in the management of COPD has become clearer.

  4. Roles of Steroids in Nematodes

    Science.gov (United States)

    The inability of nematodes to biosynthesize steroids de novo and the resulting dependence of parasitic nematodes upon their hosts have enhanced the importance of elucidating the metabolism of sterols and the hormonal and other functions of steroids in nematodes. Biochemical research has revealed th...

  5. [Longterm effects of steroid therapy].

    Science.gov (United States)

    Kuna, P

    1998-01-01

    Asthma is a chronic inflammatory disease of the airways play. Anti-inflammatory drugs the fundamental role in the treatment of asthma and among them steroids are the most important. However, oral steroids may cause many serious side effects. A major breakthrough in the treatment of asthma was introducing inhaled steroids. Inhaled steroids have much less side effects than oral steroids, although they have the same anti-inflammatory activity. Long term effect of inhaled steroids can be divided into wanted and unwanted outcome. The desirable anti-inflammatory effect of steroids is reflected by lowering of bronchial hyperresponsiveness and a better control of asthma symptoms. Inhaled corticosteroid may have systemic side effects similar to those observed with oral steroids such as 1) adrenal suppression, 2) effect on bone metabolism, 3) growth suppression in children, 4) impaired skin collagen synthesis, 5) cataract, 6) metabolic disturbances, 7) effect on central nervous system. Topical side effects of inhaled corticosteroid such as oral candidiasis, dysphonia and cough effect about 10 to 30% of patients taking those drugs. Summing up it is advisable to use inhaled corticosteroid in the lower effective dose. PMID:9610231

  6. Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are anti-androgenic in the rat foetal testis

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Lesné, L.; Fol, V. Le;

    2012-01-01

    analgesics exert potent anti-androgenic effects in the male rat and several endocrine-disrupting compounds, known to alter masculinization, have also been shown to be potent inhibitors of prostaglandin (PG) synthesis similar to mild analgesics. Using a 3-day ex vivo organotypic model system based...... of indomethacin were correlated. We conclude that mild analgesics exert direct and specific anti-androgenic effects in rat foetal testis in our experimental setup and that the mechanism of action is probably uncoupled from the inhibition of PG synthesis....

  7. The rat androgen receptor gene promoter

    NARCIS (Netherlands)

    W.M. Baarends (Willy); A.P.N. Themmen (Axel); L.J. Blok (Leen); P. Mackenbach (Petra); A.O. Brinkmann (Albert); D.N. Meijer (Dies); P.W. Faber; J. Trapman (Jan); J.A. Grootegoed (Anton)

    1990-01-01

    markdownabstractAbstract The androgen receptor (AR) is activated upon binding of testosterone or dihydrotestosterone and exerts regulatory effects on gene expression in androgen target cells. To study transcriptional regulation of the rat AR gene itself, the 5' genomic region of this gene was clon

  8. Conserved steroid hormone homology converges on nuclear factor κB to modulate inflammation in asthma.

    Science.gov (United States)

    Payne, Asha S; Freishtat, Robert J

    2012-01-01

    Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity, yet it has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing (Pediatr Pulmonol Suppl. 1997;15:9-12). Despite the complex pathogenesis of asthma, steroid hormones (eg, glucocorticoids) are ubiquitous in the short-term and long-term management of all types of asthma. Overall, steroid hormones are a class of widely relevant, biologically active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they use rapid, nongenomic actions to affect cellular products. Steroid hormones comprise several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggests that each of these is part of a dynamic system of hormone interaction, likely involving an overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these 3 groups of steroid hormones (ie, glucocorticoids, sex steroid hormones, and secosteroids), identifying nuclear factor κB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (eg, glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be a better understanding of the interplay of classic, nonclassic, and nongenomic steroid hormone functions. However, clues from the conserved homology steroid hormone structure and function and signaling pathways offer

  9. 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

  10. The Influence of Age of Onset and Acute Anabolic Steroid Exposure on Cognitive Performance, Impulsivity, and Aggression in Men

    OpenAIRE

    Hildebrandt, Tom; Langenbucher, James W.; Flores, Adrianne; Harty, Seth; Berlin, Heather A.

    2014-01-01

    A growing translational literature suggests that adolescent exposure to anabolic-androgenic steroids (AASs) leads to increased aggression and impulsivity. However, little is known about the cognitive effects of AASs among AAS users or the differences between adolescent and adult onset users. This study provides a test of the effects of acute naturalistic AAS use and age of onset (adolescent vs. adult) on measures of inhibitory control, planning and attention, and decision makin...

  11. Androgen receptor gene mutation, rearrangement, polymorphism.

    Science.gov (United States)

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E; Wang, Zhou

    2013-09-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.

  12. Factors affecting the enterohepatic circulation of oral contraceptive steroids.

    Science.gov (United States)

    Orme, M L; Back, D J

    1990-12-01

    Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol. PMID:2256523

  13. Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Henningsson, Susanne; Pinborg, Anja;

    2016-01-01

    Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women...... to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to...

  14. Identification of anabolic selective androgen receptor modulators with reduced activities in reproductive tissues and sebaceous glands.

    Science.gov (United States)

    Schmidt, Azriel; Harada, Shun-Ichi; Kimmel, Donald B; Bai, Chang; Chen, Fang; Rutledge, Su Jane; Vogel, Robert L; Scafonas, Angela; Gentile, Michael A; Nantermet, Pascale V; McElwee-Witmer, Sheila; Pennypacker, Brenda; Masarachia, Patricia; Sahoo, Soumya P; Kim, Yuntae; Meissner, Robert S; Hartman, George D; Duggan, Mark E; Rodan, Gideon A; Towler, Dwight A; Ray, William J

    2009-12-25

    Androgen replacement therapy is a promising strategy for the treatment of frailty; however, androgens pose risks for unwanted effects including virilization and hypertrophy of reproductive organs. Selective Androgen Receptor Modulators (SARMs) retain the anabolic properties of androgens in bone and muscle while having reduced effects in other tissues. We describe two structurally similar 4-aza-steroidal androgen receptor (AR) ligands, Cl-4AS-1, a full agonist, and TFM-4AS-1, which is a SARM. TFM-4AS-1 is a potent AR ligand (IC(50), 38 nm) that partially activates an AR-dependent MMTV promoter (55% of maximal response) while antagonizing the N-terminal/C-terminal interaction within AR that is required for full receptor activation. Microarray analyses of MDA-MB-453 cells show that whereas Cl-4AS-1 behaves like 5alpha-dihydrotestosterone (DHT), TFM-4AS-1 acts as a gene-selective agonist, inducing some genes as effectively as DHT and others to a lesser extent or not at all. This gene-selective agonism manifests as tissue-selectivity: in ovariectomized rats, Cl-4AS-1 mimics DHT while TFM-4AS-1 promotes the accrual of bone and muscle mass while having reduced effects on reproductive organs and sebaceous glands. Moreover, TFM-4AS-1 does not promote prostate growth and antagonizes DHT in seminal vesicles. To confirm that the biochemical properties of TFM-4AS-1 confer tissue selectivity, we identified a structurally unrelated compound, FTBU-1, with partial agonist activity coupled with antagonism of the N-terminal/C-terminal interaction and found that it also behaves as a SARM. TFM-4AS-1 and FTBU-1 represent two new classes of SARMs and will allow for comparative studies aimed at understanding the biophysical and physiological basis of tissue-selective effects of nuclear receptor ligands.

  15. Yolk androgens reduce offspring survival.

    OpenAIRE

    Sockman, K W; Schwabl, H

    2000-01-01

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those ...

  16. Sex Steroids Do Not Modulate TRPM2-Mediated Injury in Females following Middle Cerebral Artery Occlusion(1,2,3).

    Science.gov (United States)

    Quillinan, Nidia; Grewal, Himmat; Klawitter, Jelena; Herson, Paco S

    2014-01-01

    Calcium-permeable transient receptor potential M2 (TRPM2) ion channel activation contributes to cerebral ischemic injury specifically in males. In male mice, circulating androgens are required for TRPM2 inhibition with clotrimazole (CTZ) to provide protection following experimental stroke. Sufficient levels of circulating androgens are necessary to support ischemia-induced activation of poly ADP ribose polymerase (PARP) and consequent activation of TRPM2 channels. In this study, we tested whether differences in sex steroids contribute to the lack of CTZ neuroprotection in females. Middle cerebral artery occlusion (MCAO) was performed using adult female mice that were hormonally intact, ovariectomized (OVX) or dihydrotestosterone (DHT) treated. CTZ or vehicle was administered at the time of reperfusion, animals were euthanized 24 h later and brains and serum were collected. Infarct analysis revealed no effect of CTZ in intact females or females lacking endogenous sex steroids (OVX). Interestingly, treatment of female mice with the potent androgen receptor agonist DHT had no effect on ischemic injury and did not permit CTZ neuroprotection. Similarly, DHT-treated females did not exhibit increased levels of ADPribose, the TRPM2 ligand generated by PARP, following ischemia. No differences in TRPM2 or androgen receptor expression were observed between males and females. These data suggest that the lack of TRPM2 activation in females following experimental stroke is not due to the presence of estrogen or the absence of androgens. In conclusion, our data demonstrate that while circulating androgens are necessary for PARP-mediated TRPM2 injury in males, they are not sufficient to produce TRPM2 activation in females. PMID:26464961

  17. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis.

    Science.gov (United States)

    Handa, Robert J; Weiser, Michael J

    2014-04-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, prior to generating an appropriate response is the animal's reproductive status. Thus, PVN neurons express androgen and estrogen receptors and receive input from sites that also express these receptors. Consequently, changes in reproduction and gonadal steroid levels modulate the stress response and this underlies sex differences in HPA axis function. This review examines the make up of the HPA axis and hypothalamo-pituitary-gonadal (HPG) axis and the interactions between the two that should be considered when exploring normal and pathological responses to environmental stressors. PMID:24246855

  18. [Steroid hormones and the activity of the central nervous system].

    Science.gov (United States)

    Szukalski, B; Wieniawska-Szewczyk, E; Lipska, B

    1979-01-01

    Steroid hormones, i.e., corticosteroids, estrogens, androgens and progestogens are formed in the adrenal cortex, male gonads, and the female placenta. Relatively little is known of their influence on behavior and their neuroendocrine function. On the cellular level, the rate of increase of RNA message to produce albumen and avidin is directly proportionate to the presence of steroids and their amount. Corticosteroid receptors are found in the thymus, liver, spleen and heart. The brain has receptors both for the corticosteroids and the sex hormones. These receptors are scattered throughout different regions of the brain, but the synthetic glucocorticoid dexamethasome is found only in the pituitary which accounts for its role in stopping the secretion of ACTH. Testosterone undergoes metabolic changes in the brain, affecting behavior. The A chain undergoes an enzyme reduction to 5aDHT and androstandiol. Following enzyme changes, the A chain of male testosterone can become female estradiol. Laboratory tests prove that sexual behavior in males is affected only by those androgens that can convert to estrogens, while in females it is dependent on the conversion of testosterone to estrogen. Lately psychiatrists have become very interested in the catechol estrogens, fairly new metabolites of estradiol which are produced in the hypothalamus and contain 2 hydroxyl groups (as compared with the 1 hydroxyl in estrogens). Catechol estrogens block estradiol receptors, behaving like antiestrogens. Researchers are investigating the possibility of signaling the desired neural messages without the concomitant effects that estrogen produces, through using catechol estrogens. They are examining this natural derivative of estradiol which may affect among others: sexual behavior, maturity, depression, migraines, and epileptic seizures.

  19. Anabolic steroids and male infertility: a comprehensive review.

    Science.gov (United States)

    de Souza, Guilherme Leme; Hallak, Jorge

    2011-12-01

    What's known on the subject? and What does the study add? The negative impact of AAS abuse on male fertility is well known by urologists. The secondary hypogonadotropic hypogonadism is often highlighted when AAS and fertility are being discussed. On the other hand, the patterns of use, mechanisms of action and direct effects over the testicle are usually overseen. The present study reviews the vast formal and "underground" culture of AAS, as well as their overall implications. Specific considerations about their impact on the male reproductive system are made, with special attention to the recent data on direct damage to the testicle. To our knowledge this kind of overview is absolutely unique, offering a distinguished set of information to the day-by-day urologists. For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. Initially, these substances were restricted to professional bodybuilders, becoming gradually more popular among recreational power athletes. Currently, as many as 3 million anabolic-androgenic steroids (AAS) users have been reported in the United States, and considering its increasing prevalence, it has become an issue of major concern. Infertility is defined as the failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse, with male factor being present in up to 50% of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS, specially oriented to urologists, is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient axial inhibition, and the more recent experimental reports

  20. Fate of endogenous steroid hormones in steer feedlots under simulated rainfall-induced runoff.

    Science.gov (United States)

    Mansell, D Scott; Bryson, Reid J; Harter, Thomas; Webster, Jackson P; Kolodziej, Edward P; Sedlak, David L

    2011-10-15

    Steroid hormones pose potential risks to fish and other aquatic organisms at extremely low concentrations. To assess the factors affecting the release of endogenous estrogenic and androgenic steroids from feedlots during rainfall, runoff, and soil samples were collected after simulated rainfall on a 14-steer feedlot under different rainfall rates and aging periods and analyzed for six steroid hormones. While only 17α-estradiol, testosterone, and progesterone were detected in fresh manure, 17β-estradiol, estrone, and androstenedione were present in the surficial soil after two weeks. In the feedlot surficial soil, concentrations of 17α-estradiol decreased by approximately 25% accompanied by an equivalent increase in estrone and 17β-estradiol. Aging of the feedlot soils for an additional 7 days had no effect on estrogen and testosterone concentrations, but androstenedione concentrations decreased substantially, and progesterone concentrations increased. Androstenedione and progesterone concentrations in the surficial soil were much higher than could be accounted for by excretion or conversion from testosterone, suggesting that other potential precursors, such as sterols, were converted after excretion. The concentration of androgens and progesterone in the soil were approximately 85% lower after simulated rainfall, but the estrogen concentrations remained approximately constant. The decreased masses could not be accounted for by runoff, suggesting the possibility of rapid microbial transformation upon wetting. All six steroids in the runoff, with the exception of 17β-estradiol, were detected in both the filtered and particle-associated phases at concentrations well above thresholds for biological responses. Runoff from the aged plots contained less 17α-estradiol and testosterone, but more estrone, androstenedione, and progesterone relative to the runoff from the unaged plots, and most of the steroids had a lower particle-associated fraction.