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Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal

Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal women, such as FemhrtTM (Simon et al., 2003). Thus, EE is prescribed clinically to women at ages ranging from puberty through reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young, female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection. For these studies, the low and medium doses correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to the range of doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. For each study, cognition was evaluated with a battery of maze tasks tapping several domains of spatial learning and memory. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; this was seen for both cyclic and tonic regimens. Cyclic and tonic delivery of low EE, a dose that corresponds to doses used in the clinic today, resulted in transient and null impairments, respectively, on cognition.
ContributorsMennenga, Sarah E (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Baxter, Leslie C. (Committee member) / Olive, Michael F. (Committee member) / Arizona State University (Publisher)
Created2012
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Description
For animals that experience annual cycles of gonad development, the seasonal timing (phenology) of gonad growth is a major adaptation to local environmental conditions. To optimally time seasonal gonad growth, animals use environmental cues that forecast future conditions. The availability of food is one such environmental cue. Although the importance

For animals that experience annual cycles of gonad development, the seasonal timing (phenology) of gonad growth is a major adaptation to local environmental conditions. To optimally time seasonal gonad growth, animals use environmental cues that forecast future conditions. The availability of food is one such environmental cue. Although the importance of food availability has been appreciated for decades, the physiological mechanisms underlying the modulation of seasonal gonad growth by this environmental factor remain poorly understood.

Urbanization is characterized by profound environmental changes, and urban animals must adjust to an environment vastly different from that of their non-urban conspecifics. Evidence suggests that birds adjust to urban areas by advancing the timing of seasonal breeding and gonad development, compared to their non-urban conspecifics. A leading hypothesis to account for this phenomenon is that food availability is elevated in urban areas, which improves the energetic status of urban birds and enables them to initiate gonad development earlier than their non-urban conspecifics. However, this hypothesis remains largely untested.

My dissertation dovetailed comparative studies and experimental approaches conducted in field and captive settings to examine the physiological mechanisms by which food availability modulates gonad growth and to investigate whether elevated food availability in urban areas advances the phenology of gonad growth in urban birds. My captive study demonstrated that energetic status modulates reproductive hormone secretion, but not gonad growth. By contrast, free-ranging urban and non-urban birds did not differ in energetic status or plasma levels of reproductive hormones either in years in which urban birds had advanced phenology of gonad growth or in a year that had no habitat-related disparity in seasonal gonad growth. Therefore, my dissertation provides no support for the hypothesis that urban birds begin seasonal gonad growth because they are in better energetic status and increase the secretion of reproductive hormones earlier than non-urban birds. My studies do suggest, however, that the phenology of key food items and the endocrine responsiveness of the reproductive system may contribute to habitat-related disparities in the phenology of gonad growth.
ContributorsDavies, Scott (Author) / Deviche, Pierre (Thesis advisor) / Sweazea, Karen (Committee member) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Warren, Paige (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Though for most of the twentieth century, dogma held that the adult brain was post-mitotic, it is now known that adult neurogenesis is widespread among vertebrates, from fish, amphibians, reptiles and birds to mammals including humans. Seasonal changes in adult neurogenesis are well characterized in the song control system of

Though for most of the twentieth century, dogma held that the adult brain was post-mitotic, it is now known that adult neurogenesis is widespread among vertebrates, from fish, amphibians, reptiles and birds to mammals including humans. Seasonal changes in adult neurogenesis are well characterized in the song control system of song birds, and have been found in seasonally breeding mammals as well. In contrast to more derived vertebrates, such as mammals, where adult neurogenesis is restricted primarily to the olfactory bulb and the dentate gyrus of the hippocampus, neurogenesis is widespread along the ventricles of adult amphibians. I hypothesized that seasonal changes in adult amphibian brain cell proliferation and survival are a potential regulator of reproductive neuroendocrine function. Adult, male American bullfrogs (Rana catesbeiana; aka Lithobates catesbeianus), were maintained in captivity for up to a year under season-appropriate photoperiod. Analysis of hormone levels indicated seasonal changes in plasma testosterone concentration consistent with field studies. Using the thymidine analogue 5-bromo-2-deoxyuridine (BrdU) as a marker for newly generated cells, two differentially regulated aspects of brain cell neogenesis were tracked; that is, proliferation and survival. Seasonal differences were found in BrdU labeling in several brain areas, including the olfactory bulb, medial pallium, nucleus accumbens and the infundibular hypothalamus. Clear seasonal differences were also found in the pars distalis region of the pituitary gland, an important component of neuroendocrine pathways. BrdU labeling was also examined in relation to two neuropeptides important for amphibian reproduction: arginine vasotocin and gonadotropin releasing hormone. No cells co-localized with BrdU and either neuropeptide, but new born cells were found in close proximity to neuropeptide-containing neurons. These data suggest that seasonal differences in brain and pituitary gland cell neogenesis are a potential neuroendocrine regulatory mechanism.
ContributorsMumaw, Luke (Author) / Orchinik, Miles (Thesis advisor) / Deviche, Pierre (Committee member) / Chandler, Douglas (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is

Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is the primary environmental cue regulating reproductive development, but must be integrated with supplementary cues relating to local energetic conditions. Photoperiodic regulation of the reproductive neuroendocrine system is well described in seasonally breeding birds, but the mechanisms that these animals use to integrate supplementary cues remain unclear. I hypothesized that (a) environmental cues that negatively affect energy balance inhibit reproductive development by acting at multiple levels along the reproductive endocrine axis including the hypothalamus (b) that the availability of metabolic fuels conveys alterations in energy balance to the reproductive system. I investigated these hypotheses in male house finches, Haemorhous mexicanus, caught in the wild and brought into captivity. I first experimentally reduced body condition through food restriction and found that gonadal development and function are inhibited and these changes are associated with changes in hypothalamic gonadotropin-releasing hormone (GnRH). I then investigated this neuroendocrine integration and found that finches maintain reproductive flexibility through modifying the release of accumulated GnRH stores in response to energetic conditions. Lastly, I investigated the role of metabolic fuels in coordinating reproductive responses under two different models of negative energy balance, decreased energy intake (food restriction) and increased energy expenditure (high temperatures). Exposure to high temperatures lowered body condition and reduced food intake. Reproductive development was inhibited under both energy challenges, and occurred with decreased gonadal gene expression of enzymes involved in steroid synthesis. Minor changes in fuel utilization occurred under food restriction but not high temperatures. My results support the hypothesis that negative energy balance inhibits reproductive development through multilevel effects on the hypothalamus and gonads. These studies are among the first to demonstrate a negative effect of high temperatures on reproductive development in a wild bird. Overall, the above findings provide important foundations for investigations into adaptive responses of breeding in energetically variable environments.
ContributorsValle, Shelley (Author) / Deviche, Pierre (Thesis advisor) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Propper, Catherine (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2018
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Description
In wild birds, the stress response can inhibit the activity of the innate immune system, which serves as the first line of defense against pathogens. By elucidating the mechanisms which regulate the interaction between stress and innate immunity, researchers may be able to predict when birds experience increased susceptibility to

In wild birds, the stress response can inhibit the activity of the innate immune system, which serves as the first line of defense against pathogens. By elucidating the mechanisms which regulate the interaction between stress and innate immunity, researchers may be able to predict when birds experience increased susceptibility to infections and can target specific mediators to mitigate stress-induced suppression of innate immune activity. Such elucidation is especially important for urban birds, such as the House Sparrow (Passer domesticus), because these birds experience higher pathogen prevalence and transmission when compared to birds in rural regions. I investigated the role of corticosterone (CORT) in stress-induced suppression of two measures of innate immune activity (complement- and natural antibody-mediated activity) in male House Sparrows. Corticosterone, the primary avian glucocorticoid, is elevated during the stress response and high levels of this hormone induce effects through the activation of cytosolic and membrane-bound glucocorticoid receptors (GR). My results demonstrate that CORT is necessary and sufficient for stress-induced suppression of complement-mediated activity, and that this relationship is consistent between years. Corticosterone, however, does not inhibit complement-mediated activity through cytosolic GR, and additional research is needed to confirm the involvement of membrane-bound GR. The role of CORT in stress-induced inhibition of natural antibody-mediated activity, however, remains puzzling. Stress-induced elevation of CORT can suppress natural antibody-mediated activity through the activation of cytosolic GR, but the necessity of this mechanism varies inter-annually. In other words, both CORT-dependent and CORT-independent mechanisms may inhibit natural antibody-mediated activity during stress in certain years, but the causes of this inter-annual variation are not known. Previous studies have indicated that changes in the pathogen environment or food availability can alter regulation of innate immunity, but further research is needed to test these hypotheses. Overall, my dissertation demonstrates that stress inhibits innate immunity through several mechanisms, but environmental pressures may influence this inhibitory relationship.
ContributorsGao, Sisi (Author) / Deviche, Pierre (Thesis advisor) / DeNardo, Dale (Committee member) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Moore, Michael C. (Committee member) / Arizona State University (Publisher)
Created2017
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Description
The impact of urbanization on wildlife is becoming an important topic in conservation. However little is known concerning the proximate mechanisms involved which enable some species to persist in cities, while others perish. Adapting to novel city environments requires individuals to maintain a functional physiological response to stressful stimuli, while

The impact of urbanization on wildlife is becoming an important topic in conservation. However little is known concerning the proximate mechanisms involved which enable some species to persist in cities, while others perish. Adapting to novel city environments requires individuals to maintain a functional physiological response to stressful stimuli, while concurrently using the necessary resources (food) needed to persist. A primary function of the stress response is the mobilization of intrinsic energy resources, and thus both requirements (energy and stress) are explicably linked. This dissertation investigates the interaction of energetic reserves and the physiological stress response in a native bird species, the Curve-billed Thrasher, within the context of this species' colonization of Phoenix, Arizona. This research uses a combination of comparative studies, statistical modeling, and experimental approaches conducted in field and captive settings to demonstrate how urban and desert populations of these species differ in energetic state and stress physiology. These studies reveal that the current energetic status of an individual bird influences the secretion of glucocorticoids (primary stress hormones) and can alter how energy reserves are used for gluconeogenesis to produce energy during acute stress. In addition, this research also identifies how differing levels of a hypothalamic neuropeptide (vasotocin) may play a role in mediating differences in stress physiology between populations. The quantity of food available and even temporal variability in its abundance may alter how native birds respond to stress. Increased body condition offsets the costs of maintaining the stress response in urban areas.
ContributorsFokidis, Haralambos Bobby (Author) / Deviche, Pierre (Thesis advisor) / Arizona State University (Publisher)
Created2010