Browsing by Subject "Estrogen"
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Item Alcohol promotes mammary tumor development through regulation of estrogen signaling(2012-05) Wong, Amy W.; Nuñez, Nomelí P.Breast cancer is the most common malignancy affecting women and the second leading cause of death among women in the United States. Alcohol consumption is one of the few modifiable risk factors for breast cancer development but the mechanism by which it contributes to mammary cancer development and progression remains unclear, although it has been suggested that estrogen is critical for this process. To determine if alcohol promotes mammary tumor development via the estrogen pathway, estrogen receptor alpha-negative (ER[alpha]-negative) MMTV-neu mice were treated with various doses of ethanol and activation of estrogen signaling was measured. Our results showed that alcohol consumption increased estrogen signaling activation, serum estrogen levels and, most interestingly, expression of ER[alpha] in tumor tissue in the ER[alpha]-negative mice. Several lines of evidence in literature suggest that ER[alpha] expression in ER[alpha]-negative cancer cells is inhibited through epigenetic regulation. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than DNA sequence changes. Thus, to determine whether alcohol may regulate ER[alpha] re-expression in ER[alpha]-negative breast cancer cells through epigenetic mechanisms, we examined the effects of ethanol on CpG methylation and histone modifications (acetylation and methylation) of two ER[alpha]-negative breast cancer cell lines, MDA-MB-231 (human) and MMTV-neu (mouse). We also examined whether the epigenetic modifications subsequently affect the recruitment of transcriptional regulation complexes to the ER[alpha] promoter to regulate ER[alpha] transcription. Results showed that alcohol promotes ER[alpha] re-expression in these ER[alpha]-negative cell lines and that this effect was associated with decreased CpG methylation, an overall increase of histone acetylation and decrease of histone methylation, and an alteration in the enrichment of the ER[alpha] transcriptional regulation complexes (pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1) at the ER[alpha] promoter, which may contribute to cancer cell progression. In addition, we found that the inhibition of ER[alpha] by tamoxifen specifically blocks the effects of alcohol on ER[alpha] reactivation. To determine how alcohol promotes cell invasive ability, a critical process for cancer progression, we examined the role of two genes, metastasis suppressor Nm23 and integrin alpha-5 ITGA5, which we identified to be important for alcohol-induced breast cancer cell invasion. It has previously been shown that estrogen may regulate Nm23 expression and that estrogen regulation may be important for ITGA5-mediated cancer progression. Our results showed that alcohol promotes cancer cell invasion through the down-regulation of Nm23, which led to the subsequent increase of ITGA5 and increase of cell invasion. Collectively, data from my research strongly supports and provides evidence that alcohol promotes breast cancer development and progression through the regulation of estrogen signaling.Item Alcohol, obesity, and estrogen regulate mammary tumorigenesis through adiposity and the PI3K/Akt signaling pathway(2010-05) Hong, Jina; Nuñez, Nomelí P.; Ciolino, Henry P.; Hursting, Stephen D.; Mills, Edward M.; Wong, Paul K.Breast cancer is the most common cancer and the second leading cause of cancer deaths among women in the United States. Alcohol consumption increases breast cancer risk in women. It is unclear whether the effects of alcohol on mammary tumorigenesis are modified by body weight or exogenous estrogen. To determine if the effects of alcohol on mammary tumors are modified by body weight, mice of different body weights (lean, overweight, obese) consuming water or alcohol were injected subcutaneously with mammary cancer cells. To determine if the effects of alcohol on mammary tumors are modified by estrogen, pellets delivering estrogen were implanted into female mice, followed by subcutaneous mammary cancer cell injections. Results show that alcohol-consuming mice were more insulin sensitive and developed larger tumors sooner than water-consuming mice (p<0.05). Our data show obese mice developed larger tumors than lean mice. Exogenous estrogen triggered the loss of body fat, induced insulin sensitivity, and suppressed tumor growth. Obese mice had higher levels of insulin, IGF-1, leptin, and VEGF. The only mammary tumor growth factors increased by alcohol consumption were leptin and VEGF (p<0.05). In addition, activation of the PI3K/Akt signaling pathway was induced by alcohol and obesity in mammary tumors. Furthermore, alcohol increased the invasiveness of breast cancer cells in a dose-dependent manner, but also decreased a metastasis suppressor gene Nm23. Collectively, my dissertation suggests that alcohol consumption, obesity, and estrogen treatment regulate mammary tumorigenesis through hormones associated with adipose tissues and the PI3K/Akt signaling.Item Biodegradation of Estrogenic Steroidal Hormones(2011-10-21) Kim, Sang HyunNatural and synthetic estrogens are some of the most potent hormones detected in the environment. Agriculture fields often release higher concentrations of natural estrogens to the environment, but wastewater treatment plants (WWTPs) commonly release higher concentrations of synthetic estrogens. Estrogens can disrupt endocrine functions in wildlife and humans. Less attention has been paid to the fate and occurrence of estrogens in agricultural operations than WWTPs. Their fate is influenced by major mechanisms such as sorption and biodegradation. Sorption typically accounts for less than 10 percent of estrogen removal in WWTPs. However, biodegradation is a primary method for estrogen loss at high ammonia concentration in the agricultural and municipal operation. Less attention has been paid to the biodegradation kinetics of estrogens in the field application. Therefore, this dissertation focused on the occurrence of estrogens in agricultural fields and their biodegradation by a mixed culture and a pure culture. The estrogens in turkey litter amended fields might be biodegraded to some degree by turkey litter borne bacteria. The estrogen biodegradation by a mixed culture showed different mechanisms for each estrogen. E1 and E2 were easily degraded as a carbon source of the mixed culture. E3 and EE2 were favorable for cometabolic degradation by AOB. EE2 was not readily biodegraded by the mixed culture due to a steric hindrance of enzyme expression and EE2 metabolism in the ethynylgroup of EE2. The cometabolic kinetics of individual estrogen was evaluated by using a pure culture. The cometabolism of estrogen was demonstrated by a reductant model. This model appropriately estimated the cometabolic kinetics of individual estrogens. In addition, the effect of antibiotics on the hormone degradation was investigated in Sequencing Batch Reactors (SBRs). No significant difference was detected for the removal efficiency of target compounds in the SBRs in presence or absence of antibiotics (oxytetracycline and chlortetracycline) during long sludge retention time (SRT). However, the effluent organic matter (EfOM) was less decomposed with the presence of antibiotics, especially causing less degradation of the humic-like substances in EfOM. The results indicated the flux of antibiotics to WWTPs did not affect hormone degradation, but reduced the decomposition of humic-like substance. Finally, the findings from the research provide insight into how biodegradation influences estrogen removal in agricultural fields and municipal WWTPs. The models developed in this research yielded valuable predictive values for engineered systems.Item Characterization and estrogen regulation of uterine growth factor activity(Texas Tech University, 1988-08) Beck, CandaceEstradiol-17B has been shown to stimulate glucose transport, measured by phosphorylation of 2-deoxyglucose, and stimulate DNA synthesis, as measured by 3H-thymidine incorporation, In rat uterus in vivo. Attempts to demonstrate these responses in uterine cells in primary culture and in uterine tumor cells In culture have been unsuccessful. These observations led to the hypothesis that some responses to estradiol are mediated through the local action of peptide factors. Acid extracts of rat, bovine and rabbit uterus stimulated glucose transport and DNA synthesis in uterine tumor cells and in primary cultures of rat uterine cells. The stimulation of glucose transport was of the same magnitude (1.5-to 3.0-fold) and followed the same time course (maximum stimulation at 2-3 h) as estradiol stimulation in vivo. Uteri from estradiol treated rats contained 4 times more glucose transport-stimulating activity as did control rat uteri. The activity was acid and heat stable, was inactivated by trypsin, but not removed by dextran-coated charcoal treatment. The activity eluted in 6-12 kDa range on Sephadex G-50. DNA synthetic activity in rat uterine homogenates was elevated 3-fold within 18-24 h after estradiol injection and remained elevated with subsequent Injections. The growth-promoting activity was acid and heat stable, was reduced by trypsin but not reduced by treatment with dextran-coated charcoal. Gel filtration showed molecular weight heterogeneity with activity eluting at MW 10,000-30,000. The effect of purified growth factors on DNA synthesis in primary cultures of rat uterine cells was examined. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-B (TGFB) had no effect on 3H-thymidine incorporation under optimal conditions of incorporation. Relaxin and multiplication stimulating activity (MSA) demonstrated a stimulatory effect only at high concentrations, 207% of control at 100 |ag/ml and 175% of control at 100 ng/ml, respectively. Insulin stimulated incorporation 350% at 100 ng/ml, insulinlike growth factor-l (IGF-I) stimulated incorporation 300-400% at 10-100 g/ml, and platelet-derived growth factor (PDGF)stimulated incorporation 450% at 3 units/ml. When the positive effectors (insulin, IGF-I, MSA, and PDGF) were analyzed either combined or individually in the presence of uterine extract, the level of stimulation was greater than the maximum stimulation bserved with extract alone and approached that seen with 10% serum. Uterine extracts from estradiol treated and control rats were analyzed for IGF-I by radioimmunoassay. IGF-I was elevated 500-1000% in estradiol treated extracts relative to control levels. In summary, estradiol increases the growthpromoting activity and glucose transport-stimulating activity of uterine extracts. IGF-I was a positive stimulator of DNA synthesis in primary uterine cultures and was elevated in uterine extracts. This growth factor may be involved in the stimulation of DNA synthesis In rat uterus by estradiol.Item Development of testing systems to analyze strength of hormonally treated ligaments and stability of fixation devices(Texas Tech University, 2000-08) Ngo, KhaiThis thesis presents the results of two distinct research projects. The first project involved an investigation into the causes of injuries to anterior cruciate ligaments (ACL), while the second study dealt with the methods for treating hip fractures. Both studies involved developing a methodology for experimental testing, which included the design of the test apparatus, the test parameters, and the data acquisition system. The methodologies were designed to accurately simulate the physiological behavior of bones and ligaments. In the first project, the objective was to develop a method to analyze whether estrogen had a detrimental effect on the strength of the ACL. This would help to explain why female athletes are 3 to 10 times more likely to injure their ACL than their male counterparts. Initially, strain rates of 117%/s, 273%/s, and 490%/s were utilized to determine the strength of the ACL. It was determined that the strength tended to decrease with irrcreasing strain rate; however, only strain rates of 117%/s and 490%/s showed a statistical significance in strength reduction of 28.8%. More importantly, a comparison of an estrogen treated group to a control group showed a statistically significant decrease of 37.7% in the strength of the ACL. In addition, the study showed that the implants used to treat the specimens with estrogen had no significant effect on the properties of the ACL. Furthermore, the modes of ACL failure were consistent with the cases observed in clinical studies. That is, all specimens in the strain rate study underwent ligamentous tears and/or bone-ligament interface tears, as did 83% of the estrogen controlled specimens. The second project involved the development of the methodology to quantify the stability of fixation devices used to treat reverse obliquity intertrochanteric hip fractures. Determination of the optimal implant design to treat these types of fractures might help to decrease the high rate of unsuccessful recovery typically seen with these types of injuries. The objective of this research was to design a test apparatus and procedure to simulate the physiological behavior of human femurs. In addition, a data acquisition system for recording displacements and strains experienced by the femur was developed.Item Energy Restriction Effects on Estrogen Status and the Skeletal Response to Loading(2011-10-21) Swift, Sibyl NicholeModerate energy restriction in young, exercising women attenuates the positive effects of exercise on bone density. Studies have shown that in the absence of adequate levels of circulating estrogen, there may not be enough functional estrogen receptor-a (ER-a) to respond adequately to loading. The experiment described in this document is significant because this model has not been explored under conditions of energy restriction (EnR) which are known to reduce circulating estrogen levels; it has been tested only in ovariectomized animals. The central hypothesis of this research is that reductions in estrogen due to EnR limit the ability of bone to respond to mechanical loading (LOAD) through a down-regulation of ER-a. Study one determined which nutrient?s (calcium or energy) restriction (-40 percent) had the greatest negative effects on the skeletal integrity of exercising female rats and whether exercise (EX) could mitigate these deleterious changes. EnR caused detrimental effects in many of the structural properties of bone; however EX attenuated losses in cancellous bone. Study two ascertained whether EX maintained cancellous bone mass in female rats subjected to graded EnR (-20 or -40 percent) and whether changes in endocrine factors were related. EX preserved cancellous bone volume and osteoblast activity under both levels of EnR, in addition to total body lean mass and bone mineral content. A similar maintenance of serum insulin-like growth factor and estradiol occurred in the EX EnR(40 percent) group suggesting that these changes may be related to the protective effects of EX. Study three determined the effects of 40 percent EnR on bone formation rate to LOAD in young adult female rats and tracked alterations in ovarian function (estradiol). Although higher than non-loaded animals, the response of bone to LOAD in EnR animals was dampened in comparison to energy-replete animals. The experiments described in this document are significant because these are the first experiments to explore the relationship between EnR and estrogen levels on cancellous bone response to LOAD. This is particularly important for physically active, energy restricted women because cancellous bone in these women will not experience the same effects of loading which can increase their risk for developing osteoporosis.Item Estrogen and the aging brain of male rats(2016-12) Nutsch, Victoria Lynn; Dominguez, Juan M.; Gore, Andrea C., 1964-; Hofmann, Hans; Cummings, Molly; Gonzales, RuebenGonadal steroid hormones exert an influence on many aspects of neurobiology in men, including memory, learning and sexual dysfunction. Though testosterone is the main circulating gonadal steroid hormone in males, estradiol is also important, and together these hormones play complementary roles. While the specific roles of estrogen have been studied to some extent in young adults, little is known during aging, when sexual behavior can become impaired. I used a rodent model to examine estradiol’s role in sexual behavior and gene expression in 3 regions, selected for their importance in behavioral neuroendocrine functions and high concentrations of estrogen receptors: the medial preoptic area (mPOA), medial amygdala (MeA), and bed nucleus of the stria terminalis (BnST). My studies focused first on how age and sexual experience affects expression and activation of estrogen receptor α (ERα) and androgen receptor (AR) after sexual behavior in aging intact males. Quantification of neurons expressing hormone receptors in the mPOA revealed that neither ERα nor androgen receptor (AR) showed an age-related change in expression in the mPOA. While both ERα and AR were activated after copulation, the age-related changes were specific to ERα in the central mPOA. There were only mild deficits in sexual behavior. Serum estradiol was also elevated in both aged and copulating animals, but estradiol concentrations only correlated with sexual behavior in aged animals. In a second study, I determined how hormone deprivation (castration) and replacement with estradiol caused changes to gene expression in the mPOA, BnST and MeA. Each region had unique patterns of gene expression in response to aging and estradiol treatment. The mPOA only had changes in expression as a result of hormone administration, while the BnST had primarily age-related changes. The MeA had the greatest number of affected genes, mainly interactions between estradiol treatment and aging. These studies emphasize the importance of estradiol in aging males, and the need for continued study on its role in neuroendocrine and sexual function.Item Estrogen modulates adiposity and protects against obesity-associated inflammation, oxidative stress, and insulin resistance(2012-05) Stubbins, Renee Elaine; Núñez, Nomelí P.; Berrigan, David; Comuzzie, Anthony; deGraffenried, Linda; Hursting, Stephen D.Obesity is associated with numerous co-morbidities, such as chronic low-grade inflammation, oxidative stress, insulin resistance, cardiovascular disease, and some cancers. However, the role of estrogen in the susceptibility to obesity and its co-morbidities is not clear. To determine the role of estrogen in the above morbidities, we used C57BL/6J mice (15/group): 1)males 2)nonovariectomized females (novx) 3)ovariectomized females (ovx) and 4) ovariectomized females supplemented with estrogen (ovx-E), which were randomized to receive a 30% calorie-restricted, low-fat or high-fat diet. Our results showed that male and ovx-female mice were more susceptible to obesity compared to novx-female and ovx-female+E mice. Specifically, we observed that estrogen protected novx-female and ovx-female+E mice from adiposity and glucose intolerance by decreasing adipocyte size and key adipogenic and lipogenic mRNA expression levels. Further experimentation established that estrogen decreased abdominal adiposity by decreasing the number of large adipocytes. Our findings implied that estrogen stimulated lipolysis in novx-female and ovx-female+E mice. Additionally, the enlarged adipocytes observed in the male and ovx-female mice were accompanied with crown-like structures surrounding necrotic adipocytes and F480+ macrophages and elevated mRNA expression levels of CD68, IL6, and TNF[alpha]. Lastly, male and ovx-female mice exhibited liver steatosis, elevated serum ALT levels, and increased insulin resistance. To determine if there were sex differences in oxidative stress, we showed that estrogen protected the novx-female and ovx-female+E mice from adipose tissue oxidative stress as evidenced by fewer γH2AX stained nuclei and lower iNOS, P47x, GP90x, but higher catalase mRNA levels. In order to further understand the role of estrogen in adipocyte inflammation, we differentiated 3t3L1 pre-adipocytes in charcoal-stripped FBS +/- 1nM estrogen. Our findings mimicked our in vivo results; the presence of estrogen significantly decreased adipogenesis and down regulated IL6, TNF[alpha], and GP90x in 3t3L1 adipocytes. Additionally, using 4-hydroxytamoxifen, we demonstrated that the protective effects of estrogen on IL6 and TNF[alpha] mRNA expression were blocked; suggesting that estrogen could mediate its anti-inflammatory effects through ERα. In conclusion, this dissertation demonstrates that estrogen protects female mice from obesity-associated inflammation, oxidative stress, and insulin resistance by altering adipocyte morphology possibly through ER[alpha].Item Estrogen Receptor Beta and p53 Play Integral Roles in Estradiol Mediated Protection against Colon Tumor Development(2012-10-19) Weige, CharlesHormone replacement therapy and estrogen replacement therapy have shown the ability to reduce risk of colon cancer development in clinical and animal studies, but in vitro research has been unable to reproduce an estradiol (E2) induced response in colon cancer cell lines. We demonstrated that young adult mouse colonocytes (YAMC, non-malignant colonocytes) exhibit an anti-proliferative response to E2 treatment. These cells demonstrate reduced cell culture growth and increased apoptosis in response to E2. YAMC cells containing an activated Ras mutation are considered to be malignantly transformed, and lose the ability to respond to E2 treatment. Fulvestrant (ICI) was used as an estrogen receptor antagonist to determine that these results were estrogen receptor mediated. Furthermore, this effect was demonstrated to require the presence of ER? through the use of a transgenic ERbeta knockout mouse. In these mice, the presence of E2 significantly reduced the formation of azoxymethane induced premalignant lesions. Since YAMC cells exhibit an anti-proliferative response to E2 treatment, we utilized isogenic YAMC cell lines with and without a dominant negative p53 mutation to demonstrate that this E2 induced action involves p53 activity. E2 treatment results in increased p53 transcriptional activity and a pro-apoptotic change in expression of p53 downstream targets. Presence of the dominant negative p53 mutant nullifies these effects of E2 treatment. The involvement of p53 in the previously described protection against AOM induced premalignant lesions, was investigated using wild type and heterozygous p53 knockout (Het p53KO) mice. The reduction in p53 protein corresponded to reduced effectiveness of E2 treatment on the prevention of premalignant lesion formation in Het p53KO mice. In summary, our data indicate that E2 treatment induces anti-proliferative responses in non-malignant colonocytes and protects against the formation of carcinogen-induced premalignant lesions. These effects require the presence of functional ER? and p53. Further studies are required to more thoroughly elucidate the specific interactions and downstream effects of ER? and p53 in response to E2 stimulation.Item Mechanisms of transcriptional activation of estrogen responsive genes in breast cancer cells(2009-06-02) Chen, Chien-ChengEstrogen receptor (ER) acts as a ligand-activated transcription factor that regulates the expression of genes. The genomic mechanisms of ER action include ligand-induced dimerization of ER which binds estrogen responsive elements (EREs) in the promoters of target genes. There are also nongenomic mechanisms of ER action which are associated with membrane bound or cytosol ER-dependent activation of various protein-kinase cascades which also influence expression of target genes. Egr-1 is an immediate-early gene induced by 17?-estradiol (E2) in the rodent uterus and breast cancer cells. Deletion analysis of the Egr-1 promoter identified a minimal E2-responsive region that contained serum response element (SRE3) which bound Elk-1 and serum response factor (SRF) in gel mobility shift assays. Hormone-responsiveness of Egr-1 in MCF-7 cells was specifically inhibited by PD98059, a MAPKK inhibitor, but not by LY294002, an inhibitor of PI3-K. These results contrasted with the hormone-dependent activation of the SRE in the c-fos promoter, which was inhibited by both PD98059 and LY294002, suggesting that Egr-1, like c-fos, is activated through non-genomic pathways of estrogen action but through activation of different kinases. COUP-TFs are orphan nuclear receptors expressed in a variety of tissues where they regulate biological functions and organogenesis. In this study, we investigated coactivation of ER? by COUP-TF1 in cell lines transiently cotransfected with the pERE3 construct. COUP-TFI coactivated ER?-mediated transactivation, but unlike many other coactivators, COUP-TFI also enhanced transactivation of ER? when cells were cotransfected with the TAF1-ER? mutant or the 19c-ER? mutant. These data indicate that helix 12 of ER? is not required for coactivation by COUP-TFI when AF-1 of ER? is intact. However, when the AF-1 of ER? is deleted, the intact AF-2 function is required for coactivation by COUP-TFI. Analysis of multiple COUP-TFI deletion mutants showed that the DNA-binding domain and C-terminal region of COUP-TFI were important for coactivation of ER?. Point mutations of the DNA-binding domain of COUP-TFI resulted in loss of interactions with ER?, suggesting that the DNA-binding domain of COUP-TFI is important for its coactivation activity facilitating interactions with ER?. These results demonstrate that COUP-TFI coactivated ER? through a non-classical LXXLL-independent pathway.Item Nervous system differences between the sexes and across the menstrual cycle(2014-12) Tenan, Matthew Sheridan; Griffin, Lisa; Hackney, Anthony C; Brothers, Robert M; Marti, Carl N; Dingwell, JonathanSex hormones have in vitro effects on the nervous system. Furthermore, the effects of estradiol and progesterone metabolites have neurologic responses on the motor system, evidenced by transcranial magnetic stimulation studies. Sex hormone effects on the nervous system may underlie some of the sex discrepancies seen in athletic performance, injury and cardiovascular events. Investigating sex differences is often complicated by hormonal oscillations across the menstrual cycle; therefore, the aims of this research were to investigate sex and menstrual cycle effects on the motor and cardiovascular systems and the interaction of these two systems. In study 1, motor unit (MU) recruitment patterns of the vastus medialis (VM) and vastus medialis oblique (VMO) were examined in males and females at five menstrual cycle phases. Initial discharge rate between the VM and VMO were different only in females. This VM/VMO discharge discrepancy was only evident in females during the ovulatory and mid luteal menstrual phases. Study 2 examined the frequency domain relationship of the VM and VMO MUs between the sexes and across the menstrual cycle. Males have 256% to 741% greater odds of having coherent MU oscillations in the common drive band than females, indicating a greater common rate modulation. Further evidence indicated MU pairs from the VMO and VM/VMO have 228% and 212% greater odds of having beta band oscillations than the VM, indicating control of those muscle groups has a common cortical modulation. Study 3 looked at changes in the autonomic nervous system across the menstrual cycle via heart rate variability analysis. Heart rate variability decreases from the follicular to the luteal phases of the menstrual cycle, indicating a decrease in parasympathetic control. In study 4, the time and frequency domain relationship between electrocardiogram and MU discharge timing was examined between the sexes and across the menstrual cycle. The time domain relationship indicated that both males and females have MU time lag centered between 20-25 milliseconds, with an apparent modulation of this relationship across the menstrual cycle. The findings from this series of studies indicate that there are differences between the sexes which are often modified by the menstrual cycle in females.Item Reproductive aging & long-term hormone replacement therapy in the rhesus macaque(2014-08) Naugle, Michelle Marie; Gore, Andrea C., 1964-Menopause is a natural transition heralded by the cessation of menstrual cycles and ovulation, and it occurs in all women at an average of about 50 years of age. While not a disease, menopause is often accompanied by symptoms that interfere with the quality of life and these symptoms are due to the relatively abrupt deprivation of E2 and P4 experienced during reproductive aging. Reproductive aging consists of changes in the synthesis and release of hormones from the hypothalamus, pituitary and gonad, which make up the HPG axis. Because gonadal hormones play critical roles in many systems throughout the body and brain, not just reproduction, treatment of menopausal symptoms to date largely involves hormone replacement therapy (HRT) with E2, P4 or their combination. While not intended to treat other neurobiological symptoms beyond hot flushes, HRT has the potential to exert widespread actions due to the abundance of hormone receptors throughout the nervous system. Thus, a fuller understanding of the neurobiology of menopause is badly needed. Although much of the research into the mechanisms that underlie reproductive aging focuses on ovarian failure and follicular atresia (cell death), there is evidence that there are significant alterations in the function of the neuroendocrine levels - the hypothalamus and pituitary - that also contribute to this process. As the mean age of the population increases, the number of post-menopausal women continues to grow with broad economic, healthcare and social costs. It is increasingly important to understand the complex mechanisms underlying reproductive aging and the effects of HRT. In this dissertation, I focus on the question of how the female non-human primate hypothalamus changes both with aging and in response to steroid hormone treatments.Item Sex steroid hormones regulate responses to social challenge and opportunity in the convict cichlid, Amatitliana nigrofasciata(2011-05) Sessa, Anna Kristina; Hofmann, Hans A.Steroid hormones play an important role in modulating behavioral responses to various social stimuli. However, relatively little is known about how hormones respond to social stimuli and their modulation of subsequent behavior. Variation in the hormonal regulation of behavior across species has complicated the overall understanding of the hormone-behavior dynamic. In order to further elucidate the interplay of hormones and behavior in social situations, we exposed males of the monogamous convict cichlid Amatitliana nigrofasciata to three social stimuli: gravid female, intruder male and nonsocial neutral stimulus. We used a repeated exposure paradigm to create behavioral profiles and explore how sex steroid hormones respond to and regulate social behavior. Results show clear behavioral profiles in different social situations with 11-KT acting as the active androgen, increasing in response to social stimuli. Pharmacological manipulations using androgen and estrogen receptor agonists and antagonists exposed complex control over digging behavior based on social context, showed a unique decrease in aggressive behavior due to blocking the androgen receptors and a ubiquitous drug effect on vertical display. Results create well defined context-specific behavior profiles and extends our understanding of particular social behavior and how sex steroid hormones are involved in social situations and the behavioral response.Item The chemical behavior of estrone and 17beta-estradiol in the environment(Texas A&M University, 2007-09-17) Ullman, Jeffrey LaytonThe endogenous hormones estrone and 17????-estradiol support vertebrate growth and development, but slight increases above ambient concentrations may paradoxically induce endocrine disruption, leading to increased frequencies of reproductive disorders and cancer in humans and wildlife. Livestock excrete estrogenic compounds which can lead to surface and groundwater contamination. Limited information exists concerning estrogen fate and transport, as exposure concerns have recently arisen. This study examined the chemical behavior of estrone and 17????-estradiol with the goal of elucidating manure management principles applicable to animal feeding operations (AFOs). Both compounds indicated that they are susceptible to physicochemical and biological decomposition. Photolysis yielded 27- and 35-day half-lives for estrone and 17????-estradiol at pH 7, respectively, based on test conditions. 17????-estradiol photolysis exhibited a slight pH-dependent behavior. Mineralization produced half-lives ranging from 7 to 15 days for estrone and 3 to 7 days for 17????-estradiol. Indigenous microbial populations did not demonstrate a lag phase and therefore appeared to have been well acclimated to degrading these compounds. Anaerobic lagoon supplements did not affect mineralization rates. The compounds had partition coefficients ranging from 2 to 4.4 mL g-1, depending on soil characteristics. Estrone and 17????-estradiol had a higher absorptivity to soils with greater clay content and organic matter. Once sorbed, binding appeared largely irreversible with minimal desorption. Column experiments detected no estrone in the leachate for the finer textured soils, while estrone had completely migrated through the loamy fine sand after 7 pore volumes. Hypothetical scenarios, simulated using HYDRUS-1D, evaluated the combined effects of soil texture and the values obtained for sorption and mineralization on leaching. Model results indicated rapid leaching in loamy sand, while sandy clay loam and clay yielded significantly slower estrone and 17????-estradiol movement with concentrations 1 to 3 orders of magnitude lower. Data suggest that estrogens applied to sandy soil may leach and contaminate groundwater, especially in the presence of shallow water tables. Sandy clay loam and clay likely present minimal risk for subsurface mobility, but simulated accumulation near the soil surface may promote transport via overland flow. Sound manure management practices will likely reduce off-site transport of estrogens originating from AFOs.Item The effects of estrogen on the intestinal nutrient uptake in channel catfish(Texas Tech University, 2000-05) Tipton, Holly AnnOver the past two decades, a number of researchers have found that the gastrointestinal absorption of a diverse group of sugars, amino acids and ions can be modulated by the actions of specific hormones. Because steroids have also been found to increase the growth and food conversion efficiency in animals, interest in this area has grown. In this study, both the in-vitro (short-term) and in-vivo (long-term) effects of estrogen (E2) were studied on the intestinal transport of channel catfish. In conjunction with this overall experimental objective, a number of related projects ensued. The first of these, the discovery of putative Eo receptors (ER) in catfish intestine by immunocytochemistry, prompted the initial study of the effects of Ej on intestinal transport. Secondly, nutrient transport was characterized by assessing any differences seen between sexes using the everted sleeve technique. A tissue viability smdy was also performed to examine how long intestinal tissue remained viable in the in-vitro test system. Since catfish in this study varied in age from young (< 1 year) to three years of age, seasonal and developmental changes in the transport of the amino acid of interest, L-alanine, were followed. The results indicate that short-term (min-to-hours) and long-term (hours-todays) E2 treatments regulate nutrient uptake of the amino acid, L-alanine, in specific gut regions. Taken together, all the results indicate that age, endogenous E2 levels and E2 receptor expression may interact to determine E2's regulation of the channel catfish intestinal transport.Item The role of estrogen receptors in the contribution of constrictor prostanoids to aortic coarctation-induced hypertension(2009-05-15) Sellers, Minga MiownThis study investigated the effects of selective estrogen receptor (ER) agonists on constrictor prostanoid (CP) function and on the development of mean arterial pressure (MAP) in aortic coarctation-induced hypertension (ACIH). Female Sprague-Dawley rats were divided randomly into four groups: intact (INT), ovariectomized (OVX), OVX + ER? selective agonist (4, 4?, 4?-(4-Propyl-[1H]-pyrazole-1, 3, 5-triyl)trisphenol; OVX+PPT), or OVX + ER? selective agonist (2,3-bis(4-Hydroxyphenyl)-propionitrile; OVX+DPN). Rats were then subjected to abdominal aortic coarctation (hypertensive, HT) or sham surgery (normotensive, NT). PPT, DPN or vehicle treatments were given daily as a subcutaneous injection. MAP was measured every other day at 2-14 days after coarctation. Mesenteric arterioles were harvested 12-14 days after coarctation for isometric tension studies to examine concentration-responses to VP. Basal and VP-stimulated prostanoid release and mRNA and protein levels of ER? and ER? (using real time RT-PCR and immunoblotting) were measured in separate groups of arterioles. MAP was higher in INT-HT, OVX+PPT-HT and OVX+DPN-HT than in OVX-HT after 12 days. Vascular reactivity to VP was greater in OVX+PPT-NT rats than in other groups. There were no significant differences in vascular reactivity to VP in HT groups. Blockade of thromboxane receptor (TP) with SQ 29,548 (TP receptor antagonist) did not have a significant effect in any groups. Inhibition of intracellular calcium release with simvastatin (blocker of IP3 mediated calcium release) was greater in NT than in HT groups, and greater in OVX- and DPN-treated groups than in INT and PPT-treated groups. VP-stimulated release of thromboxane (TXA2) and prostacyclin (PGI2) were highest in INT-HT and OVX+PPT-HT rats. Neither mRNA nor protein expression of ERs changed significantly in response to selective ER agonist treatment or during hypertension. Selective ER? stimulation with PPT during development of ACIH resulted in similar effects to those seen in INT rats for CP release, VP reactivity of mesenteric arterioles and MAP, while selective stimulation of ER? only increased MAP. While ER? is capable of modulating most of the effects of estrogen on the vasculature, ER? has stimulatory effects on MAP during the development of ACIH that merit further investigation. Further studies of the vascular actions of ER? and ER? may lead to better hormonal therapies that successfully prevent and/or treat cardiovascular disease in post-menopausal women.