Browsing by Subject "Hormone receptors"
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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 Synthetic selective and differential receptors for the recognition of bioanalytes(2006) Wright, Aaron Todd; Anslyn, Eric V.This dissertation consists of five chapters. The first chapter provides an in-depth background of supramolecular chemistry and differential recognition. The first chapter also elaborates upon the necessary requirements for successful application of chemosensor assays and arrays. Additionally, sensing mechanisms and chemometric pattern recognition is described for clarification of the research conducted in chapters 2- 5. Chapter 2 discusses the synthesis and employment of a metalated receptor for the selective recognition of the tripeptide His-Lys-Lys. A receptor was synthesized with two peptide arms emanating outward from a metal ligand core using both solution and solid phase chemistry. UV/Vis titrations were used to determine binding constants for various amino acids and tripeptides to the synthetic receptor:Cu(II) complex. The receptor:Cu(II) complex was found to be selective for His-Lys-Lys over other tripeptides, amino acids, and protected amino acids. viii Chapter 3 describes the synthesis and application of a fluorescent chemosensor for the recognition of unfractionated and low-molecular weight heparin. Heparin is a commonly used clinical anticoagulant for surgical situations and post-operative outpatient care. Due to the high selectivity of the receptor for heparin, studies in crude serum were attempted. It was found that the receptor was selective for heparin in serum. Therefore, fluorescent calibration charts were prepared for quantifying heparin at clinical concentrations using the synthetic receptor. This research is one of very few to be published regarding the creation of synthetic receptors with sufficient selectivity for activity in biological media. Chapter 4 describes the combinatorial synthesis of two resin-bound receptor libraries for use in differential recognition studies. The two libraries, in conjunction with an indicator-uptake assay, were used for the detection and discrimination of three proteins and two glycoproteins as well as four tripeptides and three tripeptide mixtures using pattern recognition protocols. Chapter 5 discusses the preparation and screening of a metalated receptor library. A colorimetric mimic of a tachykinin hormone, α-neurokinin, was created and used to screen the receptor library. Seven selective receptors were identified and subsequently sequenced to determine their molecular architecture. The receptors were resynthesized and employed in solution phase binding studies with α-neurokinin.