Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

Thesis (Ph. D.)--University of Delaware, 2006. / Principal faculty advisor: John T. Koh, Dept. of Chemistry and Biochemistry. Includes bibliographical references.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references (leaves 183-214). Also available in electronic version.

No description available.

published_or_final_version / Zoology / Master / Master of Philosophy

published_or_final_version / abstract / Biological Sciences / Doctoral / Doctor of Philosophy

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy

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. / text

This study was designed to evaluate the possible existence of masked gonadotropin binding sites in the corpus luteum of the rhesus monkey. Pretreatment of macaque luteal particulates and cells with neuraminidase increased LH binding. In vitro exposure to alcohols also enhanced LH binding to these preparations. Ethanol modulation of LH binding was a time- and temperature-dependent process. The optimal concentration of ethanol for enhancing LH uptake was inversely proportional to the incubation temperature. Longer straight-chain alcohols were more potent than ethanol in increasing LH binding. Ethanol and neuraminidase increased the number of binding sites with no affect on affinity. Moreover, the effects of ethanol and NA were additive. Since alcohols and temperature are modulators of membrane fluidity, we examined the hypothesis that the unmasking of gonadotropin binding sites may be related to changes in the fluid state of the lipid bilayer of the luteal membrane. First, membrane fluidity was estimated from the fluorescence polarization of the membrane probe diphenylhexatriene. Conditions which resulted in enhanced gonadotropin binding (1-8% ethanol, increased temperature), increased the fluidity of luteal membranes. Moreover, changes in gonadotropin binding were highly correlated (r = -0.97) with changes in membrane fluidity under these conditions. Pretreatment of luteal particulates with neuraminidase had no apparent effect on membrane fluidity. Second, gonadotropin receptors were removed from the luteal membrane by detergent solubilization, and the effects of ethanol on soluble receptors were compared to those on receptors associated with the lipid bilayer. Solubilization resulted in the recovery of 50% more gonadotropin binding sites than are available in particulate preparations of the corpus luteum; these sites displayed lower affinity for gonadotropin. Moreover, conditions which increase LH binding to luteal particulates (1-8% ethanol at 25C) decreased LH uptake by soluble receptors. The data suggest that two populations of LH binding sites are masked within the membranes of the monkey corpus luteum. The ability of two markedly different agents, alcohol and neuraminidase, to increase LH binding indicates the diverse mechanisms may modulate the masking/unmasking of gonadotropin receptors in target cell membranes. As such, changes in membrane fluidity may play an important role in this response.