Master of Science, The Ohio State University, 2022, Health and Rehabilitation Sciences

Background: Testosterone-cortisol ratio (TCR) and free testosterone-cortisol ratio (fTCR) are biochemical values that describe the levels between the respective hormones. These markers are suggested to be potential indicators of an imbalance between training stress and recovery. High bouts of physical activity, coupled with low energy availability, have been suggested to significantly impact hormone function. Endurance athletes have a unique proclivity to experience low energy availability due to the culture and significant metabolic demand of their sport. This predisposition may affect hormone status. Objective: The purpose of this study was to examine TCR and fTCR in male endurance runners and identify correlations between dietary factors and training variables. Methods: This cross-sectional study analyzed data from 41 white male endurance runners between the ages of 20-50 years old, who ran a minimum of 4 days and 40 miles per week for at least two years. Dietary factors were estimated using a self-reported three- day food record. Physical activity was measured via accelerometer concurrent with three consecutive days of food log documentation. Blood was drawn in the morning of an iDXA visit after a 9-hour fast and analyzed for serum variables. Results: Mean TCR and fTCR in this population was 34.35 +/-13.93 and 0.83 +/-0.34 ng:mcg per dL, respectively. Significant and inverse Spearman's correlations were identified between both cortisol ratios and weekly mileage. Dietary factors did not demonstrate significant correlations with TCR and fTCR directly, but exploratory variables, like total testosterone and cortisol, displayed trends for correlation. Conclusion: Training mileage inversely correlates with TCR and fTCR biochemical markers. Sports medicine professionals, including sports dietitians, should investigate athletes training volume and intensity to gain more insight into the signs and symptoms of potential hormonal irregularities associated with overtr (open full item for complete abstract)

Committee: Jackie Buell (Advisor); Jill Clutter (Committee Member); Julie Kennel (Committee Member) Subjects: Nutrition; Sports Medicine

Master of Science in Biological Sciences, Youngstown State University, 1998, Department of Biological Sciences and Chemistry

Purpose: This study was conducted to investigate the role of testosterone in regulating the relaxation of isolated rat corpus cavernosum strips in vitro. Materials and Methods: Male rats were divided into treatment groups of intact, castrate, and castrate with testosterone replacement. Norepinephrine was added to contract each of the tissue strips. Next, sodium nitroprusside, experiment I, or 8-bromo-cGMP, experiment II, was added to relax the cavernosum tissue. Percent relaxations were recorded for each treatment group at each dose level. Results: Sodium nitroprusside was added to the norepinephrine contracted tissues in doses of 10 -4 and 10 -3 M. In this experiment, castration significantly reduced tissue responsiveness to sodium nitroprusside and testosterone replacement restored the response to intact levels. In the second experiment 8-bromo-cGMP was added to the norepinephrine contracted tissues in doses of 10 -5 and 10 -4 M 8-bromo-cGMP 10 -4 M was significantly less effective in relaxing tissue from castrate animals as compared to intact controls. Again, testosterone treatment restored the response to intact levels. Conclusions: Our results show a clear role of testosterone in regulating the ability of corpus cavernosum tissue to relax when treated with sodium nitroprusside or 8-bromo-cGMP in vitro. In addition, the data suggests that testosterone regulates sites distal to the formation of cGMP in this smooth muscle relaxation pathway.

Committee: Robert Leipheimer (Advisor) Subjects:

Bachelor of Arts, Capital University, 2022, Biological and Environmental Science

Polychlorinated biphenyls (PCBs) are synthetic organic chemicals used in various industrial and commercial settings, including electrical equipment. Over many decades PCBs have found their way into the environment and have been shown to cause severe health defects in both animals and humans. Previous research indicates that PCBs have had adverse effects on the reproductive health of many organisms. This study was designed to examine correlations between PCBs and the reproductive health of both men and women. The National Health and Nutrition Examination Survey (NHANES) assesses the health and nutritional status of millions of Americans. It combines interviews and physical examinations of participants on a two-year cycle, beginning in 1999. The NHANES database is being used to statistically analyze the PCB levels in human blood samples over twenty years and compare them to reproductive hormone levels of both sexes. To date, this research has found no significant correlation between the levels of PCBs in the blood and the levels of sex hormones in both men and women. Most individuals have both detectable levels of PCBs and hormones in their blood. But because there is no way to track the results of each person individually, it is difficult to tell if there is a correlation. This ongoing study will provide a further understanding of the impacts of PCBs on public health and help design further research with the NHANES database.

Committee: Kerry Cheesman (Advisor) Subjects: Biology; Health

PHD, Kent State University, 2019, College of Education, Health and Human Services / School of Lifespan Development and Educational Sciences

This phenomenological qualitative study explored men over the age of 40 years old using medically monitored testosterone therapy. Eight participants were purposefully sampled and interviewed to gain a better understanding of their experiences of masculinity. Data were analyzed and two overarching themes emerged: (a) masculinity is correlated to performance, and (b) masculinity is related to quality of life. Each participant's lived experience showed these emergent and often overlapping themes that create a better framework to engage men in counseling by better understanding their locus of motivation. The findings of this study revealed themes that men use to define themselves as men and how they perceive their social, occupational, and familial roles. Additional research further exploring these roles and the motivations influencing them is warranted. A new sample using an alternate qualitative methodology such as narrative, case study, or ethnography can add to a deeper, richer understanding of the phenomenon.

Committee: MARTIN JENCIUS PHD (Committee Co-Chair); JASON MCGLOTHLIN PHD (Committee Co-Chair); DALE CURRY PHD (Committee Member); MAUREEN BLANKEMEYER PHD (Other) Subjects: Counseling Education; Counseling Psychology

Doctor of Philosophy (PhD), Ohio University, 2017, Clinical Psychology (Arts and Sciences)

While there is considerable evidence for neurobiological and neuropsychological impairments in clinical or incarcerated psychopaths, there is less research examining these domains among nonincarcerated adults with high levels of psychopathic traits (i.e., subclinical psychopaths). The present study examined differences in neuroendocrine and autonomic functioning, affective processing, and self-reported and behavioral aggression in young adult males with high levels of subclinical psychopathy, compared to young adult males with low levels of psychopathic characteristics. Participants completed self- report questionnaires assessing psychopathic traits, aggression, drug and alcohol use, and other demographic information. They provided salivary cortisol samples before and 25 minutes after participating in a social stressor. Participants completed an affective processing task, during which their skin conductance reactivity was measured. They also engaged in a behavioral aggression task. Contrary to hypotheses, no differences between psychopathic groups were found in basal cortisol levels or cortisol reactivity following a social stressor, skin conductance reactivity while viewing negative pictures, valence ratings while viewing negative pictures, or aggression during a laboratory aggression task. Consistent with hypotheses, males with higher levels of psychopathic traits reported engaging in more physical and verbal aggression compared to the group with lower levels of psychopathic traits. Exploratory analyses suggested differential relationships between psychopathy subtype factors and outcome variables, with the factor associated with the secondary psychopathy subtype positively and consistently related to all self-reported aggression. The results suggest there is a need to control for and examine the characteristics associated with the two subtypes of psychopathy in studies of the psychopathy construct, particularly as they relate to various forms of aggression.

Committee: Julie Suhr PhD (Advisor) Subjects: Clinical Psychology; Personality Psychology; Psychology

Doctor of Philosophy, The Ohio State University, 1975, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1974, Graduate School

Committee: Not Provided (Other) Subjects: Agriculture

Doctor of Philosophy, The Ohio State University, 1972, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1965, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1966, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1955, Graduate School

Committee: Not Provided (Other) Subjects: Biology

PHD, Kent State University, 2016, College of Arts and Sciences / Department of Biological Sciences

Circadian rhythms of physiology and behavior are driven by a circadian clock located in the suprachiasmatic nucleus of the hypothalamus. This clock is synchronized to environmental day/night cycles by photic input, which is dependent on the presence of mature brain-derived neurotrophic factor (BDNF) in the SCN. Mature BDNF is produced by the enzyme plasmin, which is converted from plasminogen by the enzyme tissue plasminogen activator (tPA). In this study, we evaluate circadian function in mice lacking functional tPA. KO mice have normal circadian periods, but show an increased proportion of daily wheel-running activity during the day and a slightly reduced overall level of wheel-running activity. When placed on daily cycles of restricted food availability, the difference between activity level disappears. Despite the increased wheel-running activity in KO mice, neither they nor wild type mice entrain to 24-hour cycles of restricted food availability in constant darkness. When daily restricted feeding occurs with the animals housed in a skeleton photoperiod (15 min of light at the beginning and end of the day only), some though not all of the difference between genotypes is eliminated. These data suggest that tPA plays a fundamental role in regulating the response of circadian clocks to both photic and feeding signals. In addition, female mice exhibit significantly less FAA than males, and we sought to investigate the mechanism for this difference. Females showed no daily changes in FAA that might correspond to the estrous cycle, suggesting that variation in estrogen levels are not responsible for the difference between males and females. Therefore we hypothesized that testosterone might be responsible for sex differences in FAA. Male and female mice were randomly selected for gonadectomy (GDX) and sham procedures. Following surgical procedures mice were individually housed in 12:12 LD and placed on 4-hr daily restricted feeding. In males, orchiectomy sign (open full item for complete abstract)

Committee: Eric Mintz PHD (Committee Chair); Colleen Novak PHD (Committee Member); John Johnson PHD (Committee Member); Mary Ann Raghanti PHD (Committee Member); Stephen Fountain PHD (Committee Member) Subjects: Behavioral Sciences; Biology; Neurosciences

PHD, Kent State University, 2016, College of Arts and Sciences / Department of Psychological Sciences

Anxiety disorders are the most common mental disorder with nearly 30% of individuals meeting criteria for an anxiety disorder over the course of their lifetime, generating significant personal, financial and emotional burden. Additionally, women are 60% more likely than men to be diagnosed with an anxiety disorder, such as PTSD. Inappropriate fear that occurs in normally safe environments, or fear generalization, is a key symptom of many anxiety disorders. The current set experiments explores sex differences in the generalization of fear and identifies mechanisms by which estradiol affects fear generalization. Results demonstrate that females generalize fear at a faster rate than males, and this process is driven, in part, by estradiol. However, in males, estradiol acts to attenuate generalization rather than to induce generalization. In fact, testosterone also attenuates generalization in gonadectomized males and does so through conversion into estradiol via aromatase. Estradiol impacts generalization through effects on memory retrieval rather than memory acquisition/consolidation. In females, estradiol acts through activation of cytosolic ERß within the dorsal CA1 region of the hippocampus and the anterior cingulate cortex (ACC), but not the ventral CA1 region of the hippocampus. Finally, estradiol-induced generalization in females appears to be a result of augmented glutamatergic signaling within the dorsal CA1 and ACC; blocking glutamate receptor activation attenuates estradiol-induced generalization. These mechanisms can help explain the discrepancies in prevalence rates for anxiety disorders between males and females, and are also crucial for development of more effective, and potentially sex-specific, treatments for anxiety disorders such as PTSD.

Committee: Aaron Jasnow Ph.D (Advisor); David Riccio Ph.D (Advisor); Stephen Fountain Ph.D (Committee Member); Karin Coifman Ph.D (Committee Member); John Johnson Ph.D (Committee Member); Heather Caldwell Ph.D (Committee Chair) Subjects: Animals; Behavioral Psychology; Biology; Endocrinology; Experimental Psychology; Neurobiology; Pharmacology

Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2016, Biomedical Sciences (Orthopaedic Sciences)

Bone marrow adipose tissue (BMAT) is an endocrine organ and heterogenic adipose depot that is located throughout the body in the marrow of bones. BMAT has the potential to modulate bone microenvironment. Recent studies have found that it is region-specific and species specific under various metabolic pathophysiological conditions such as aging, caloric restriction, diabetes, and sex steroid deficiency. Previously, our lab concluded that BMAT has phenotypic characteristics of white adipose tissue (WAT), brown adipose tissue (BAT), and brown-like or beige adipose tissue. This project investigated whether sex steroids control the bone morphology and phenotype of bone marrow adipose tissue in male and female animals. Results indicate that there are significant differences in bone mass and fat deposition of the tibia of adult male and female mice. However, sexual dimorphism in the expression of those adipose tissue markers in the BMAT was not observed in the qRT-PCR analysis of the proximal tibia of OVX and ORX animals.

Committee: BEATA LECKA-CZERNIK (Advisor); MARTIN SKIE (Committee Chair); A CHAMPA JAYASURIYA (Committee Member); EDWIN SANCHEZ (Committee Member); JENNIFER HILL (Committee Member) Subjects: Biomedical Research; Endocrinology

Doctor of Philosophy, The Ohio State University, 2015, Kinesiology

Men that engage in high volumes of long distance running have been previously shown to demonstrate low testosterone concentrations. However, both the cause and the consequences of the condition remain undetermined. The purpose of this study was to identify the pathogenesis of the condition as well as to determine whether symptoms that are typically seen in other populations with reduced testosterone are present. 9 men (Age: 36.3 ± 9.2 years; Height: 180.0 ± 8.8 cm; Weight: 77.2 ± 6.8 kg) performing an average of 81 ± 14 km per week of running for the past 12 months (EHMC) were compared to 8 men who served as control (CONT) subjects (Age: 30.8 ± 6.3 years; Height: 176.9 ± 5.2; Weight: 77.3 ± 10.7 kg) performing no regular exercise for the past 12 months. Blood samples were taken every 15 minutes beginning at 08:00 and continuing until 12:00, for a total of 17 blood draws. Blood was analyzed for testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) and cortisol (C). Subjects underwent a dual x-ray absorptiometry (DEXA) scan to assess bone density and body composition. Subjects also completed the Aging Male Symptoms (AMS) questionnaire and a Food Frequency Questionnaire (FFQ). As expected, T concentrations were significantly (P = 0.05) reduced in the EHMC group compared with CONT at all time points. There were no differences in LH. The EHMC group demonstrated significantly (P = 0.05) higher AMS scores (EHMC: 26.0 ± 7.1 vs CONT: 21.7 ± 5.5). There were no differences in body composition or bone density. There were no differences in energy intake (EHMC: 2710.6 ± 800.1 vs CONT: 2742.8 ± 969.0 kcal), but there was a significantly (P = 0.05) higher contribution from carbohydrate in the EHMC group (EHMC: 48.6 ± 3.8 vs CONT: 36.5 ± 9.0 %). This study was the first to document that reduced T concentrations resulting from high volumes of long distance running leads to the demonstration of hypogonadal symptoms. This study also revealed that despite runni (open full item for complete abstract)

Committee: William Kraemer Ph.D. (Advisor); Carl Maresh Ph.D. (Committee Member); Jeff Volek Ph.D. (Committee Member); Brian Focht Ph.D. (Committee Member) Subjects: Endocrinology; Kinesiology; Physiology

MA, Kent State University, 2015, College of Arts and Sciences / Department of Psychological Sciences

Periadolescence is a critical developmental period during which stress reactivity is exacerbated, and when the experience of stress can severely compromise appropriate adult stress responsiveness. However, studies of stress responsiveness tend to focus on adults, overlooking the importance of early life experiences that shape adult physiology and behavior. The current study utilizes social defeat stress and observes the immediate and long-term impact on subsequent social interaction. Initially, periadolescent mice are resistant to mild social defeat stress, resulting in social interaction similar to non-defeated controls. When the same mice are tested again throughout puberty and into adulthood, a phenotypic split is observed, where a portion of animals are susceptible to the defeat stress, resulting in significantly lower social interaction. This developmental shift seems to be mediated, in part, by the presence of testosterone but testes weights do not seem to predict differences in phenotype. Furthermore, susceptible and resistant mice have increased corticosterone following the first social defeat stress, but only mice that remain resistant into adulthood show elevated corticosterone following periadolescent social interaction. However, CRH level within the PVN increased in both stable resistant and latent susceptible groups in adulthood. Future experiments will identify mechanisms underlying the difference between phenotypes in response to early life social stress. Ultimately, these experiments will help pinpoint why only a portion of individuals develop disorders following social trauma, and how early life social stress differentially influences brain development and susceptibility adulthood.

Committee: Aaron Jasnow M (Advisor) Subjects: Endocrinology; Neurobiology; Neurosciences; Psychobiology; Psychology

Master of Science (MS), Wright State University, 2012, Biochemistry and Molecular Biology

p53 activation through different cellular senescence pathways can trigger cell cycle arrest via regulation of p53 target genes. One such target gene is YPEL3 which is expressed upon binding of tumor suppressor protein p53 at its p53 binding sites (Kelley, 2010). The ability of p53 to induce YPEL3 gene expression led to the discovery that YPEL3 is one of several p53 target genes which induce cellular senescence (Kelley, 2010). Additionally YPEL3 can be regulated independently of p53 by estrogen signaling through estrogen receptor α (Tuttle, 2011). The loss of estrogen receptor α or removal of estrogen induces YPEL3 gene expression and leads to cellular senescence, indicating that estrogen bound to estrogen receptor α represses YPEL3 gene expression (Tuttle, 2011). Although YPEL3 induction results in cellular senescence the mechanism by which YPEL3 elicits cellular senescence is not well understood. It is also unknown if other steroid hormones, such as testosterone play a role in regulating YPEL3 gene expression To further understand hormone regulation of YPEL3 the first part of this thesis tested if testosterone regulates YPEL3 gene expression in MCF7 breast cancer cells and LnCAP prostate cancer cells. Like MCF7 breast cancer cells, LnCAPs cultured in the absence of steroid hormones induced YPEL3 expression indicating that YPEL3 gene expression in LnCAPs is repressed by steroid hormones. This induction of YPEL3 expression was blocked by the addition of testosterone to LnCAP cells. In contrast the addition of testosterone to steroid deprived MCF7 cells resulted in YPEL3 induction. Based on the results in LnCAP prostate cancer cells and MCF7 breast cancer cells it appears that testosterones effect on YPEL3 gene expression is tissue specific. In part two of this thesis MCF7 and IMR90 cells were employed to determine if over expression of YPEL3 leads to increased reactive oxygen species (ROS) levels. First an optimized method for detecting reactive oxygen species leve (open full item for complete abstract)

Committee: Steven Berberich PhD (Advisor); Gerald Alter PhD (Committee Member); Michael Markey PhD (Committee Member) Subjects: Biochemistry

Master of Science (MS), Wright State University, 2008, Biological Sciences

The purpose of this study was to determine the effects of a nutritional supplement, Mass FX, on muscular strength, body composition, and blood chemistries in resistance-trained adult males. Eight subjects, mean age 25 +/- 3.02 years, were randomly assigned to two groups (n=4). Each group was given either Mass FX or a Placebo in a double-blind manner to be taken orally for six weeks (4caps/day regardless of bodyweight). For the duration of the study, both groups were following the same training program and a diet customized to each subject's bodyweight in conjunction to the supplementation. Data were analyzed using Analysis of Covariance (ANCOVA) with a Bonferroni correction resulting in a family-wise level of significance of α = 0.05, to avoid inflation of the Type I error. To confirm results, an independent samples t-test using a Bonferroni correction with a family-wise level of significance of α=0.05 was performed. Using ANCOVA, the groups were significantly different for the Bench Press outcome; whereas using the independent samples t-test, the two groups were significantly different for Bench Press and Free Testosterone. The results of this study indicate that supplementation with Mass FX induced better improvements than Placebo in muscular strength as measured by the bench press (p<0.05). Other measures in muscular strength, body composition, and free testosterone showed improvements, but were not statistically significant (p>0.05). No adverse effects on selected clinical health markers: complete blood count with differential, hepatic (AST, ALP, ALT), lipids (TC, TGs, LDL, VLDL), and renal (creatinine, BUN) were observed from Mass FX supplementation (Group significance p>0.05). Mean difference (Post-Pre) in total and free testosterone concentrations exhibited apparent increases in the Mass FX group, in contrast to Placebo in which reductions in both mean difference total and free testosterone concentrations were observed. Lack of significance in the remaining v (open full item for complete abstract)

Committee: Roberta Pohlman PhD (Advisor); Mark Mamrack PhD (Committee Member); David Goldstein PhD (Committee Member) Subjects: Biology; Nutrition; Sports Medicine

Doctor of Philosophy, The Ohio State University, 2005, Pharmacy

There is an urgent need to develop new forms of contraception that men are willing to use. Currently, testosterone-based hormonal contraceptives represent the most promising approach. However, testosterone demonstrates little activity after oral administration due to rapid hepatic elimination, precluding its use in oral contraceptives for men. The long-term safety of testosterone, as it relates to psychological function, cardiovascular disease, and prostate disease, is also of concern. Non-steroidal selective androgen receptor modulators (SARMs) may provide an alternative to the use of testosterone, with the advantages of oral bioavailability, tissue selectivity, lack of influence on lipoproteins, and androgen receptor (AR) specificity. We hypothesized that SARMs would mimic the pharmacologic activity of testosterone in vivo and can safely replace testosterone as a component of hormonal male contraceptives. SARMs discovered previously demonstrated potential applications in the treatment of muscle wasting, osteoporosis, and benign prostate hyperplasia in animal models. However, low or no CNS effects were observed, which precluded their use for hormonal male contraception as a single regimen. Novel AR ligands were designed and synthesized using integrated knowledge of molecular modeling, structure-activity-relationships, and pharmacokinetics and metabolism of known SARMs. In the current studies, the abilities of these compounds to bind AR and to stimulate (agonist) or inhibit (antagonist) AR-mediated transcriptional activation (Chapter 2) were determined. Compounds with high AR binding affinity and potent stimulatory activity in transcriptional assays were further investigated in castrated rats (Chapter 3) for their pharmacologic effects. Key in vitro and in vivo structure-activity-relationships of these ligands were identified. Differences in the pharmacokinetics and metabolism between SARMs resulted in a contradiction between the in vitro and in vivo pharmacologic a (open full item for complete abstract)

Committee: James Dalton (Advisor) Subjects: