Prenatal ethanol (E) exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. E rats show HPA hyperresponsiveness to stressors and altered reproductive function in adulthood. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that gonadal hormones play a role in mediating ethanol effects on HPA function. To address this possibility, two studies were conducted to test the hypothesis that the differential alterations in HPA activity observed in E compared to control males are mediated, at least in part, by ethanol-induced changes in HPG effects on HPA regulation. The first study compared the effects of gonadectomy (GDX) on HPA and HPG activity in adult male offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) dams. There were no differences among groups in basal testosterone levels under intact conditions. However, E males showed increased adrenocorticotropin but blunted testosterone and luteinizing hormone (LH) responses to restraint stress compared to PF and/or C rats, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels. GDX eliminated these differences among groups. The second study explored dose-related effects of testosterone on HPA regulation. Testosterone had less of an inhibitory effect on stress-induced CORT and LH increases in E than in PF and C males. Furthermore, testosterone had a reduced effect on central corticotropin-releasing hormone pathways, but an increased effect on central AVP pathways in E compared to PF and/or C males. Importantly, reduced androgen receptor (AR) mRNA levels, possibly reflecting downregulation of AR in key brain areas, may counteract the increased inhibitory AVP signals upstream from the paraventricular nucleus, and thus contribute to the HPA hyperresponsiveness seen in E males. Together these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure. The capacity of testosterone to regulate HPA activity is altered in E males, with some effects mediated by the nutritional effects of ethanol. These changes would impair the ability to maintain homeostasis in E animals and have implications for the development of secondary disabilities in children with Fetal Alcohol Spectrum Disorder. / Medicine, Faculty of / Graduate

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Modulation of the male reproductive system occurs as a result of exposure to endocrine disrupting compounds (EDCs) in different life stages. The effects of EDCs on the male reproductive system include infertility, decreased sperm count, function and morphology, abnormal development of secondary sex characteristics, reproductive function and sexual behavior, as well as decreased libido. Phytochemicals are naturally occurring, biologically active chemical compounds in plants. They are divided into different groups. Isoflavonoids and lignans, are the two major groups of phytoestrogens. Phytoestrogens of teas, coffee and buchu have many beneficial effects on body systems such as antimutagenic, antidiabetic, anti-inflammatory, antibacterial and antiviral properties. They also elicit many adverse events, for example, heavy consumption of green and black tea may cause liver damage and added unwanted effects when combined with other herbal beverages. Chronic heavy consumption of coffee is positively correlated to acute myocardial infarction and can elevate serum cholesterol levels. Rooibos tea decreases steroidogenesis by steroid secreting cell lines.This study investigated the effects of these beverages on the male reproductive system, using a minced testes method for determination of cell viability and hormone (testosterone) production. The first objective of this study was to optimize protein supplement for in vitro testosterone production using human serum albumin (HSA) and foetal bovine serum (FBS). Testicular cultures were prepared and exposed overnight to different concentrations of both sera and then incubated for 4 hours with or without luteinizing hormone (LH). The results showed that addition of protein supplements (HSA or FBS) did not have a significant effect on testosterone production. The second objective of this study was to investigate the effects of green tea, black tea, rooibos tea, coffee and buchu on cell viability of testicular cultures. Cells were treated overnight with varying concentrations of the plant extracts followed by incubation with/without LH for 4 hours. The effects of the plant beverages on cellular protein production were determined by the Bradford assay. The results showed that treatment of cells with varying concentrations of the plant extracts (with/without LH-treatment) had no significant effect on total cellular protein. The third objective of this study was to investigate the effects of black, green and rooibos teas, coffee and buchu on testosterone production by testicular cultures. The results obtained from these experiments showed that rooibos tea and buchu did not affect testosterone production in the presence or absence of LH. The results also indicated that green tea, black tea and coffee inhibited testosterone production by mouse testis cultures in the presence of LH, but not in the absence of LH. Black tea was the most potent inhibitor of testosterone synthesis by mouse testis cultures (IC50= 48 μg/ml), followed by coffee (IC50= 64 μg/ml) and green tea (IC50= 173 μg/ml). Green tea, black tea and coffee inhibited LH-stimulated testosterone synthesis, suggesting that these beverages may impair testicular steroidogenesis in mice. Thus, in spite of their acclaimed beneficial effects, consumption of these beverages in high doses raises concerns for their inhibitory effects on male reproductive function. Further in vitro and in vivo studies are warranted to determine their exact mechanisms of action on the male reproductive system in general and testicular function in particular.

This thesis focuses on women's competition in female basketball players and their hormonal responses to winning and losing. We tested saliva samples of 29 female players for testosterone and cortisol which were collected in three phases: baseline samples, pregame samples and after game samples. In every collection phase we also inquired about the emotional state of mind of the respondents. Players completed a survey examining their subjective evaluation of the match result. We also used statistical data from every match, which provided an objective evidence on the players' usefulness. All the aforementioned variables were examined in relation to the testosterone and cortisol levels. The results have revealed that the cortisol levels are responsive to the match results, whereas the losing players display a significant rise of the stress hormone level after the match. The winners display only a slight increase in the cortisol levels. Testosterone levels did not prove to react to the match results. However, it was discovered that the winners exhibited higher levels of testosterone in all collection phases than their competitors. Nevertheless, the difference between the winners and the losers was not significant in any of the cases. The winners felt more positive after the match than the losers. The correlation...

The purpose of this thesis has been to investigate elements of racism in two court documents from The Court of Arbitration for Sports (CAS). The court documents deal with two regulations from the International Athletics Federation (IAAF) and the implementation of these regulations, which aim to assess womens’ participation in elite running. These regulations are based on measurements of female athletes’ testosterone levels to assess who is considered eligible to compete in the female category in elite running. The regulations have been criticized by UN Human Rights Council, which states that the regulations include racial discrimination, since the regulations are primarily aimed at women from the global South as they to a greater extent demonstrate higher levels of testosterone. The thesis has analysed whether racist discourses can be discerned in the court documents by examining statements from the IAAF and CAS when it discusses the implementation of these regulations in elite running for women.  The analysis of the court documents is based on a method of critical discourse analysis. which intends to shed light on uneven power structures due to, among other things, race. In the court documents, the content of the texts was examined according to the method. The thesis examines how women who produce higher levels of testosterone are described in relation to women who produce testosterone within the “normal” range. The thesis also examines which discourses have the most space in the court documents. The analysis is supplemented with Sara Ahmed´s theory of the phenomenology of whiteness, and Sandra Fredman´s theory of the concept of equality. The results of the thesis show that women from the global South are considered abnormal due to a socially constructed norm based on white Western ideals. Female athletes who show a higher level of testosterone come mainly from the global South. Since these athletes are more affected by the IAAF:s regulations than those from the West, it can be interpreted that these women are restricted in their freedom of movement within elite running compared to white female athletes.

Female sheep exposed to excess testosterone (T) in utero display symptoms similar to those observed in women with polycystic ovarian syndrome (PCOS). Prenatal T-treated ewes display masculinized sexual behavior and increased food-reward seeking behavior. A neural substrate critical for these goal-directed behaviors is the dopaminergic system in the ventral tegmental area. We have recently shown that in adult ewes dopamine expression in the VTA is increased by prenatal T exposure. In this thesis, I tested the hypothesis that alterations of the VTA dopamine system by prenatal-T are caused via activation of androgen (AR) and/or insulin receptors (IR). Analysis of immunohistochemical staining shows an increase of tyrosine hydroxylase (TH) expression, AR, or IR, along with changes in co-expression of AR/TH and IR/TH. These changes were blocked or reversed by prenatal treatments with flutamide or rosiglitazone, or postnatal treatments with rosiglitazone or metformin, implicating AR and IR in alterations of the VTA

The effects of testosterone (T) extend beyond reproductive behavior to the areas of cognitive and emotional functioning. While T effects on cognition have been extensively investigated, less is known about the role of T in the processing of emotional stimuli. Considering the role that T plays in aggressive behavior and dominance status, it is of particular interest to determine whether T modulates the processing of social threat. Due to their similarities to humans in brain organization, reproductive endocrinology and affective regulation, rhesus monkeys (macaca mulatta) provide an excellent model to investigate this relationship. In a within-subjects design, six male rhesus monkeys underwent treatment to suppress endogenous T and received either T or oil replacement. Tests of anxiety, attention and memory for social and non-social emotional stimuli, and risk-taking were administered to animals during both treatments. Data analyses indicate that T treatment resulted in faster response times, but had no effect on anxiety, attention or memory for emotional stimuli, or on risk-taking behavior. There are several limitations to this study that may account for the lack of effect of T and therefore, further investigation of the relationship between T and emotional processing is warranted.

Prior studies of lipid and lipoprotein levels alterations associated with the administration of danazol, a testosterone derivative, in patients treated for endometriosis have been conflicting. We administered danazol to 7 normal menstruating women and measured plasma lipid and lipoprotein cholesterol levels prior to and 2 months after treatment. Small, non-significant decreases in total plasma cholesterol and triglyceride levels were seen, largely due to a dramatic decline in one woman with type IV hyperlipoproteinemia. No significant change in low density or very low density lipoprotein cholesterol levels was seen. However, a marked (40%) reduction of high density lipoprotein cholesterol level in the mean was found. These findings have implications for the atherogenic potential of danazol, the treatment of hyperlipidemia, and the relationship between gonadal hormones and lipoprotein levels.

Recently, comparisons of "periodized" strength training methods have become a focus of sport science. Daily undulating periodization (DUP), using daily alterations in repetitions, has been developed and touted as a superior method of training. The purpose of this study is to compare traditional periodization (TRA) to DUP in Division I track and field athletes. Thirty-one athletes were assigned to either a TRA or the DUP group training programs based on sex, year, and event. Training lasted 10 weeks. There were 4 testing sessions focusing on strength characteristics. Although, trends favored the TRA group for strength and rate of force development, no significant differences were found between the groups. Significant differences (p≤0.05) in volume and the amount of improvement per volume load were found to be significantly different (p≤0.05) between the TRA and DUP groups. These data indicate that TRA is more efficient in producing strength gains than DUP.

Indiana University-Purdue University Indianapolis (IUPUI) / Enteric viruses are infectious human pathogens that initiate infection in the gastrointestinal tract. They follow a fecal-oral route of transmission and are spread by contamination of food, water, or contact between individuals. Furthermore, enteric viruses also cause significant morbidity, mortality, and economic burdens yearly. Coxsackievirus (CV) is commonly isolated among enteric viruses and is an etiological agent of hand, foot, and mouth disease, hemorrhagic conjunctivitis, and myocarditis. The virus predominantly infects infants and young children and accounts for 11% of the fatality rate in neonates. Despite CV’s impact on human health, there are no treatments or vaccines for CV infections. Using a mouse model to study a key CV, Coxsackievirus B3 (CVB3), our laboratory has found two critical factors that impact CVB3 replication and pathogenesis. First, we have demonstrated that intestinal bacteria enhance intestinal CVB3 replication. We found that certain specific bacteria (Salmonella enterica) and its cell wall components, like lipopolysaccharides (LPS), enhanced CVB3 stability and infectivity in vitro. Additionally, we found that particular constituents of LPS are required for stability to occur. These data suggest that specific bacteria may be integral in maintaining CVB3 infectivity in the intestine. Besides virus-microbiome interaction, CVB3 is also impacted by sex hormones. Using castrated mice models, we observed a sex bias to CVB3 infection, with male mice succumbing to CVB3-induced disease at an increased rate compared to female mice. Our data suggest that testosterone, a predominant male sex hormone, enhanced CVB3 intestinal replication and viral dissemination to organs in male and female mice, but lethality only in male mice. Moreover, testosterone also affected the immune response by reducing the activation of the CD8+ T cells. CD8+ T cells are required to clear the viral infection and are integral in vaccine development. In contrast, we found an enhanced CD8+ T cell response in female mice to CVB3 infection, suggesting a sex-dependent T cell response that may underlie the sex bias in disease. Overall, these data represent an essential advancement in the CV field and will help develop future therapeutics and aid in vaccine design to limit CV infections.

An organism’s spatial ecology allows for access to essential resources such as food, mates, and escape from predators. Home range size, or the total area an organism inhabits, varies in relation to numerous factors including seasonality. During the breeding season, home range size increases in males across taxa. In addition, males usually also have larger home range sizes than females. This implicates testosterone (T) as a possible mediator of this relationship. Indeed, T causes an increase in home range size of males in numerous species of lizards. In addition to T causing an increase in home range size, it also causes an increase in coloration, which is used as a signal to deter or elicit aggressive behaviors in lizards. Potentially, contests are less common in natural settings than in the lab due to this signaling despite increased frequency overlap of home ranges in males. The larger the home range size of males, mediated through an increase in T, the more overlap with conspecifics. With this increase in spatial demand, or home range size, there is often a corresponding increase in spatially related brain regions. In reptiles, these brain regions are the medial and dorsal cortices (MC and DC respectively). The increase in cortical brain region size due to an increase in spatial demand may be mediated by an increase in neurogenesis. Proliferation of neurons occurs along the ventricles and radiate to numerous regions in the brain including the MC. With respect to the MC, immature neurons, which express the protein doublecortin (DCX), migrate from the ventricles, through the inner plexiform layer and are integrated into the cell layer. Because DCX is only expressed in recently born, migrating neurons, it can be used to measure neurogenesis. In mammals and birds, neurogenesis and growth of certain brain regions is affected by steroid hormones, including T. Here we tested two hypotheses: (1) T affects the home range size of Sceloporus occidentalis and (2) cortical brain region volumes are related to home range size and/or T which is mediated through changes in rates of neurogenesis. We surgically castrated individuals and implanted subjects with either a T-filled implant or blank implant and then released them at their initial capture sites. In addition to these castrated individuals, subjects not subjected to castration served as unmanipulated controls. Home range size of individuals in the field was quantified using a global positioning system (GPS) unit and later delineating those GPS points using minimum convex polygons (MCPs). We predicted that (1) castrated, T-treated lizards and unmanipulated control lizards would have larger home range sizes than castrated, control lizards c and (2) MC and DC cortices would be larger in volume and contain more DCX-immunoreactive cells in the lizards with the highest circulating T levels and with the largest home range sizes. We found that increased T caused an increase in the number of blue abdominal scales. We found no differences in home range size relating to T. Likewise, T did not affect MC volumes. However, we did observe a decrease in DC volume with increasing plasma levels of T. Because T did not affect home range size, it follows that we did not find an effect of T on MC volume. However, the significant result of T causing a decrease in DC volume implies a possible trade off with regards to energetics and the maintenance of brain region volumes as prior research indicates that T in increases energy expenditure and decreases foraging efforts.