<p>Stem cells have the capacity for both self renewal, and to form all cell types in the body. Interestingly, so called neural stem cells (NSCs) are found in the adult human brain, which is of significance both out of a developmental perspective and from a clinical point of view. At the present moment, the regulation of neural stem cell (NSC) proliferation and fate determination is not completely understood.</p><p>The overall aim of this thesis was to study the mechanisms that regulate NSC proliferation and fate determination <i>in vitro</i> and <i>in vivo</i>. In particular, the roles of the female sex hormone estrogen and the testosterone analogue nandrolone, as well as the melanocortin α-melanocyte stimulating hormone (α-MSH), were analyzed in this context. Also, the breast cancer susceptibility gene one (BRCA-1), was studied in the brain with emphasis on regions containing NSCs.</p><p>Our findings show that estrogen and nandrolone have similar effects on NSCs; both decreased NSC proliferation and increased neurogenesis. Estrogen's ability to reduce proliferation was due to increased levels of p21, an inhibitor of cyclin dependent kinases. In contrast, no change in p21 was observed in the case of nandrolone, indicating differential regulation. Adult rats subjected to nandrolone injections had 30% reduced NSC proliferation in the dentate gyrus, indicating profound effects on NSCs <i>in vivo</i>.</p><p>The melanocortin α-MSH acted as a mitogen by increasing levels of cyclinD1 and retinoblastoma protein; as a result NSC proliferation was doubled.</p><p>Finally, BRCA-1 is expressed while NSCs proliferate, but is drastically down regulated upon differentiation, indicating that BRCA-1 could be used as a possible NSC marker.</p><p>In summary, in this thesis estrogen and nandrolone were identified as NSC regulators which decrease proliferation and positively influence neurogenesis. Also, we have identified the hormone α-MSH as a NSC mitogen, and BRCA-1 as a possible NSC marker.</p>

Stem cells have the capacity for both self renewal, and to form all cell types in the body. Interestingly, so called neural stem cells (NSCs) are found in the adult human brain, which is of significance both out of a developmental perspective and from a clinical point of view. At the present moment, the regulation of neural stem cell (NSC) proliferation and fate determination is not completely understood. The overall aim of this thesis was to study the mechanisms that regulate NSC proliferation and fate determination in vitro and in vivo. In particular, the roles of the female sex hormone estrogen and the testosterone analogue nandrolone, as well as the melanocortin α-melanocyte stimulating hormone (α-MSH), were analyzed in this context. Also, the breast cancer susceptibility gene one (BRCA-1), was studied in the brain with emphasis on regions containing NSCs. Our findings show that estrogen and nandrolone have similar effects on NSCs; both decreased NSC proliferation and increased neurogenesis. Estrogen's ability to reduce proliferation was due to increased levels of p21, an inhibitor of cyclin dependent kinases. In contrast, no change in p21 was observed in the case of nandrolone, indicating differential regulation. Adult rats subjected to nandrolone injections had 30% reduced NSC proliferation in the dentate gyrus, indicating profound effects on NSCs in vivo. The melanocortin α-MSH acted as a mitogen by increasing levels of cyclinD1 and retinoblastoma protein; as a result NSC proliferation was doubled. Finally, BRCA-1 is expressed while NSCs proliferate, but is drastically down regulated upon differentiation, indicating that BRCA-1 could be used as a possible NSC marker. In summary, in this thesis estrogen and nandrolone were identified as NSC regulators which decrease proliferation and positively influence neurogenesis. Also, we have identified the hormone α-MSH as a NSC mitogen, and BRCA-1 as a possible NSC marker.

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 drug dependence and aggression, in the male rat brain. Adult male Sprague-Dawley rats received intramuscular injections of nandrolone decanoate (3 or 15 mg/kg) or vehicle once daily for 14 days. Nandrolone decanoate pre-exposure abolished the effect of amphetamine on the 3,4-dihydroxyphenylacetic acid (DOPAC) tissue level in the hypothalamus and on the DOPAC/dopamine ratio in the hypothalamus and the hippocampus. A significant decrease of the basal extracellular DOPAC and homovanillic acid (HVA) levels could be detected in the nucleus accumbens, which remained low during the first hour following the amphetamine challenge. Nandrolone decanoate significantly reduced the activity of both monoamine oxidase A and B (MAO-A and -B) in the caudate putamen and amygdala. The gene transcript levels of MAO-B, and the dopamine D1 and D4 receptors were altered in limbic regions. No changes in transcriptional levels could be detected among the serotonin receptor genes examined. However, the density of the serotonin transporter protein was elevated in a range of aggression-related brain regions. Taken together, subchronic administration of nandrolone decanoate causes dopaminergic and serotonergic dysregulations in distinct brain regions. These areas of the brain are involved in the development of drug dependence and expression of impulsive and aggressive behaviours. These results may contribute to explain some of the behavioural changes often reported in AAS abusers, such as polydrug use and impaired impulse control.

Strength training is widely used to increase performance in sports with high physical demands. The use of drugs such as anabolic steroids among athletes is a wellknown phenomenon, and the effects of these drugs on physical performance documented. The studies presented in this thesis focused on the mechanisms of muscle fiber hypertrophy in the vastus lateralis and the trapezius muscles of strength trained elite athletes. The main hypothesis was that the muscle adaptations to strength training and anabolic steroids are muscle specific. Biopsies were obtained from the trapezius and the vastus lateralis from three groups of elite power lifters. Nine used drugs, ten did not and seven had previously used drugs. Six sedentary males served as controls. The biopsies were frozen and cut in serial cross sections. Histological and immunohistochemical staining techniques were used to analyze muscle fiber morphology and pathology. Fiber type distribution, fiber area, myonuclei number and distribution, satellite cell number and proportion of split fibers were counted and compared for the two muscles within and between the groups. The main findings were that: a) Muscle fiber hypertrophy by strength training is further increased by anabolic steroids. b) The number of nuclei per muscle fiber is higher in power lifters using anabolic steroids compared to non-steroids using lifters. c) Among power lifters who have withdrawn from anabolic steroid usage and training for several years, the number of myonuclei, both subsarcolemmal and internal, remains high. d) In active power lifters, anabolic steroids have no further effect on the number of satellite cells per fiber. e) Power lifters have a high proportion of split fibers. High intensity resistance training increases muscle strength and banned substances such as testosterone and anabolic steroids can enhance the training effects. The studies on muscle cell morphology presented in this thesis reveals that anabolic steroids and testosterone increases muscle fiber size and adds more nuclei to the muscle cell. Based on the morphological appearance of muscle sections from doped and nondoped power lifters, we conclude that testosterone and anabolic steroids enhances the hypertrophic effects of training without adding new features. The addition of myonuclei by training and doping appears to be longer lasting in some muscles than in others. The high proportion of split fibers in power lifter is probably due to high mechanical stress. The findings and conclusions in this thesis raise questions regarding relevant suspension times for athletes caught with banned substances in the body.

Abstract Title: Anabolic Androgenic Steroids – An analysis of how AAS is portrayed in Swedish media. Author: Jens Sundén Tutor: Philip Lalander Keywords: AAS, Anabolic steroids, social problems, media, drug abuse, gender The purpose of this study was to investigate how Anabolic Androgenic Steroids (AAS) are portrayed and described in the media, how AAS is constructed as a social problem, and how society in a social context uses knowledge and power for disciplinary and educational means. The study is based on the perception of AAS as a constructed social problem and analyzes the discourses surrounding AAS depicted in three Swedish newspapers. The sample was prepared on the basis that it represents different aspects of daily Swedish press. The method used in the paper is a discourse analysis with social constructivism and gender as theoretical tools used to analyze the sample material. An important conclusion of the analysis is that the use of AAS is a socially constructed problem, which incorporates both a stereotyped, aggressive male individual who desires an ideal body, and the use of AAS defined as an illegitimate abuse by society. Another important aspect of the analysis is how gender roles are highlighted in the sample and how these from a gender perspective are used to perpetuate male superiority and female subordination in society.

This is a study about gym training young men (age 18-20) and their attitude against anabolic androgenic steroids, AAS. In our study we examine if the muscular ideal in our society have any effect on young men and the young men’s attitude against their body and their training. We want to find out what attitude gym training young men have against AAS, and also what has had the influence to this attitude.          The study contains six qualitative performed interviews with young men who are training at the gym, which are based on relevant information about their training habits, nutritional supplement, influence, the muscular ideal, the gym culture and medias effect on young men when it comes to body ideals.            The young men’s attitudes is connected and compared to prior research about gym-training young men and what affects them to have a certain attitude against AAS, body and training. In our study we also use a theory by Giddens about social interaction and the late modern society we live in.           The conclusions of the result and analysis is that young men who trains at the gym for the purpose of getting bigger and in relation to the training takes nutritional supplements, have a more liberal attitude against AAS compared to those young men who doesn’t. Media, friends, equals at the gym and the gym culture are all factors that affect young men in their positive attitude in opposition to AAS.

Denna kvalitativa studie handlar om några behandlares upplevelser och erfarenheter kring vilka personer som hamnar i missbruk av anabola androgena steroider(AAS). Den belyser även vilken behanding som finns för problematiken. För att erhålla empiri används semistrukturerade intervjuer på fyra personer som arbetar med behandling av AAS. Resultatet visar att man kan kategorisera AAS-användare i tre olika grupper. När klienter kommer till behandling är det viktigt att man ser till helhetsbilden och att man ser varje individ för sig. Metoder som finns är terapi för det sjuka kroppsidealet, hjälp med träningsmissbruket, läkemedelsassisterad behandling samt annan psykosocial terapi. En intressant slutsats är att det finns hjälp att få vid AAS-missbruk, men tyvärr finns det inte resurser att hjälpa alla. Det finns fortfarande mycket kvar att lära inom ämnet och man behöver forska kring fler och bättre behandlingsmetoder som kan passa vid detta missbruk.

Syftet med föreliggande uppsats är att undersöka hur patienter och behandlare ser på vad som leder till ett bruk alternativt missbruk av anabola androgena steroider, AAS. Uppsatsen har en kvalitativ, fenomenografisk ansats. Ostrukturerade intervjuer genomfördes med fem patienter och tre behandlare vid Beroendecentrum i Örebro. Materialet analyserades med hjälp av tematisk analys. Sju teman utkristalliserade sig som resultat; Samhälle, Uppväxt, Socialt umgänge, Psykologiska sårbarheter, Attityder, Kroppsbild och Övrigt. Det omfattande resultatet kan anses visa på en komplexitet i förklaringen till vad som leder till att en individ börjar bruka eller missbruka AAS. / This study aims to examine how patients and clinicians look at what leads to the use or abuse of anabolic androgenic steroids, AAS. The study uses a qualitative phenomenographic method. The research data was collected with unstructured interviews with five patients and three clinicians at Beroendecentrum in Örebro. The research data was analyzed through the use of a thematic analysis. The results were the seven themes that emerged; Society, Childhood, Social relations, Psychological vulnerabilities, Attitudes, Body image and Other. The extensive results can be looked upon as showing the complexity in the explanation of what leads to an individuals use or abuse of AAS.

The purpose of this study was to increase understanding of factors associated with nonmedical anabolic steroid use among males ages 18-30 who do not participate in intercollegiate athletics. The Behavioral Intentions and Ergogenic Aid/Performance Enhancer use among non-intercollegiate athlete males survey instrument was developed, reviewed for content validity by a jury of experts, and pilot tested. The pilot testing results (n=25) demonstrated acceptable reliability (Cronbach’s alpha= 0.74). The final version of the Behavioral Intentions and Ergogenic Aid/Performance Enhancer use among non-intercollegiate athlete males survey instrument was administered at two distribution sites which included Ford’s Fitness Center in Lexington, Kentucky and the Johnson Center on the University of Kentucky’s campus to non-intercollegiate athlete men between the ages of 18-30 (n=121). The final version of the survey instrument was also found to be reliable (Cronbach’s alpha= 0.86).Of the 121 respondents, 7 (5.9%) reported using nonmedical anabolic steroids at least 1-2 days a week or more. A total of 9 (7.4%) men reported intending to use nonmedical anabolic steroids within the next year. Age was found to have a statistically significant association with intention to use nonmedical anabolic steroids (p=.037).Perceived behavioral control (p=.029) was found to be the strongest predictor variable of study participants’ intention to use nonmedical anabolic steroids. Muscle mass builder use (p=.011) and muscle mass builder use in combination with multivitamin use (p=.000) were found to be significant predictors of actual nonmedical anabolic steroid use. Study participants were more likely to use nonmedical anabolic steroids if they were currently using a muscle mass builder or using a muscle mass builder in combination with a multivitamin. No decision about the effectiveness of the components of perceived behavioral control (self-efficacy and control) as a one or two part construct was possible because of the small number of study participants. Two additional demographic predictor variables were found to be statistically significant with predicting the intention to use nonmedical anabolic steroids. Being a competitive bodybuilder (p=.001) was positively correlated and being satisfied with body image (p=.025) was negatively correlated with the intention to use nonmedical anabolic steroids.

Los agentes anabolizantes prohibidos por la Comisión Médica del Comité Olímpico Internacional (COI) deben estar ausentes en las muestras de orina objeto de análisis. El límite de detección está condicionado por la sensibilidad del instrumento y la relación señal/ruido debida al material biológico coextraído junto con los analitos de interés. Las nuevas exigencias de sensibilidad del COI como la detección de nuevas sustancias utilizadas en dosis sensiblemente inferiores, obliga al replanteamiento de la estrategia analítica utilizada. El objetivo general de esta tesis es: desarrollar nuevas técnicas analíticas de alta sensibilidad para la detección de esteroides y otros anabolizantes en orina humana mediante: 1.- Estudio de la cromatografía liquida capilar para la cuantificación de las concentraciones de testosterona y epitestosterona en orina humana. 2.- Estudio de la purificación de la muestra previa al análisis instrumental. - Estudio del uso de la cormatografía de inmunoafinidad (IAC) en la purificación selectiva dela muestra. - Desarrollo de procedimientos mediante cromatografía líquida de alta resolución para la purificación de fracciones en los análisis de confirmación. 3.- Incremento de la sensibilidad en el análisis instrumental. - Estudio de la formación de tert-butildimetilsilil derivados como alternativa a los trimestilsilil derivados habitualmente utilizados. - Estudio de la utilización de nueva instrumentación basada en la espectrometría de masas de trampa de iones y en tándem (MS/MS) para alcanzar la sensibilidad y selectividad requerida por los nuevos estánderes impuestos por las organizaciones internacionales del área de la salud, en particular en el deporte.