Browsing by Subject "Hormones"
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Item Synergy 2008: Annual Research Report(2008-01-01)Item THE ASSOCIATION BETWEEN AGGRESSION AND DHEA-S(2013-04-12) Marshall, HayleyPurpose: The purpose was to assess the association between aggression, including the subcategories of physical, verbal, anger, and hostility aggression, with serum DHEA-S levels in non-Hispanic Caucasian (NHC), non-Hispanic African American (AA), and Hispanic (H) women, aged 20-40 years. Methods: Data were obtained from the Racial/Ethnic Differences in Stress Age Among Women Study. This study included women 20 - 40 years of age who were not pregnant and not taking glucocorticoids. Participants also did not have cancer; endocrine disorders (e.g. Diabetes Mellitus); thyroid, parathyroid, or adrenal gland disorders; or immunologic disease (e.g. HIV, AIDS, Lupus). Participants completed self-reported questionnaires including the Aggression Questionnaire. DHEA-S levels were measured via a blood draw. Five simple linear regression models were analyzed with each category of aggression as the independent variable and DHEA-S as the dependent variable. Multiple linear regressions included the aggression category, age, and race/ethnicity. Log-transformed DHEA-S was utilized to achieve normality. Statistical significance was assessed at alphad0.05. Results: A total of 70 women with mean age of 29.4(sd=5.4) were included. There were 23 NHC, 21 AA, and 27 H participants. In crude analysis, an increase in total(p=0.019) and verbal aggression (p=0.008) was associated with a decrease in logDHEA-S. The association for physical aggression approached significance (p=0.059). After controlling for age and race/ethnicity, an increase in verbal aggression (p=0.021) was associated with a decrease in logDHEA-S. A borderline association was observed for total aggression (p=0.054). Compared to NHC, being AA was associated with a decrease in logDHEA-S in models with total, physical, and anger aggression. The association approached significance in the models for verbal and hostility aggression. An increase in age was associated with a decrease in logDHEA-S in all models. Conclusions: Results indicate there is interplay between the psychosocial factors of physical, verbal, and total aggression (the first two being physical manifestations of aggression) with DHEA-S levels. Since DHEA-S is associated with many (non)physiological processes, it is important that future clinicians understand how these biopsychosocial aspects of life can influence each patient individually. If clinicians can understand these relationships, then they can work with their patients towards a goal of both physical and psychosocial well-being.Item THE EFFECTS OF ANDROGENS ON CASPASE-1 MEDIATED SIGNALING IN OXIDATIVE STRESSED DOPAMINE NEURONS(2014-03) Holmes, Shaletha S.; Su, Chang; Singh, Meharvan; Cunningham, RebeccaParkinson’s disease (PD), a neurodegenerative disorder characterized by oxidative stress and the loss of dopamine neurons in the midbrain, affects the aging population. In fact, males have a higher risk for PD than females. While the mechanisms remain elusive, one possibility may be that androgens, such as testosterone, play a potential role. Our studies suggest that androgens can increase the expression of Caspase-1, an enzyme whose activity increases with oxidative stress and can result in mitochondrial collapse, ubiquitination, alpha-synuclein–positive lewy body accumulation, inflammation and apoptosis. Therefore, we hypothesize that in oxidative stress conditions, androgens suppress KLF4, a negative regulator of caspase-1, resulting in the increase of Caspase-1 to promote toxic protein accumulation, inflammation, and apoptotic neuronal cell death. This study is related to the role of testosterone in high levels of oxidative stress associated with aging. Purpose (a): Oxidative stress and an extensive loss of dopamine neurons in the nigrostriatal pathway are hallmarks of Parkinson’s disease (PD), a neurodegenerative disorder affecting millions of people. Males have a higher risk for PD than females. While the mechanisms remain elusive, one possibility may be that androgens, such as testosterone, play a potential role. Our studies suggest that androgens can increase the expression of Caspase-1, an enzyme whose activity increases with oxidative stress and can result in mitochondrial collapse, ubiquitination, alpha-synuclein–positive lewy body accumulation, inflammation and apoptosis. We hypothesize that in oxidative stress conditions, androgens suppress KLF4, a negative regulator of caspase-1, resulting in overexpression of Caspase-1 leading to toxic protein accumulation, inflammation, and apoptosis. Methods (b): We exposed a dopaminergic cell line (N27 cells) to a sublethal concentration of the pro-oxidant, tert-butyl hydrogen peroxide (H2O2) for 24 hrs and assessed cell viability in the presence or absence of testosterone. Results (c): Physiologically relevant concentrations of testosterone (0, 1, 10, 100 nM) failed to compromise cell viability in non-oxidatively stressed cells1. In contrast, testosterone did promote cell death in the H2O2 pre-treated cells. In H202 treated cells, testosterone increased caspase-1 expression and activation, as evidenced by an increase in cleaved caspase-1. In addition, KLF4 expression was decreased by testosterone in H2O2 treated cells. The role of KLF4 as a negative regulator of caspase-1 was confirmed in experiments showing that siRNA-mediated knockdown of KLF4 increased caspase-1 levels in H2O2 treated cells. Testosterone increased H202 mediated expression of COX2 signaling, a protein associated with inflammation. Also, testosterone decreased H2O2-induced ubiquitin expression resulting in the accumulation of toxic proteins. Further, testosterone increased H202 induced in apoptosis. Conclusions (d): Overall, these results indicate that androgens such as testosterone exert negative effects under oxidative stress conditions through the suppression of KLF4 and activation of caspase-1 signaling pathways leading to cell death. Thus, supporting a role for androgens for the gender bias observed in PD.