Rapid Metabolic Control of the HPG System

描述（由申请人提供）：这种多学科的国际合作将扩大我们对不孕症和相关并发症的理解（例如，骨质疏松症），由于营养不足，节食，过度运动，神经性厌食症，肥胖症和糖尿病。 下丘脑-垂体-性腺（HPG）系统依赖于代谢燃料的可用性，但代谢刺激的位置和性质尚不清楚。 食物限制（FR）抑制发情周期和黄体生成素（LH）的脉冲式分泌，这些作用在再喂养后数小时内逆转。 FR导致激素、神经肽和代谢事件的变化。 再喂养的快速效应将使我们能够精确定位那些发生得足够快的神经内分泌事件，以解释再喂养的影响，并忽略那些服务于生殖以外功能的较慢的变化。 放射免疫分析、免疫细胞化学、原位杂交和推挽灌注将用于测量循环激素（胰岛素、瘦素、生长激素、生长激素释放肽）和脑神经肽（例如，神经肽Y和促肾上腺皮质激素释放激素）的仓鼠和绵羊中，所述仓鼠和绵羊被随意饲喂、FR饲喂或FR饲喂然后再饲喂。 此外，FR仓鼠和绵羊将用各种大量营养素和燃料重新喂养，以确定对HPG功能快速恢复至关重要的代谢刺激。 仓鼠的四天发情周期是一致的，易于监测，这使得在阐明发情周期的某些基本要求方面取得了快速进展（Schneider实验室，美国）。 母羊较大的血液供应将使我们能够测量脉冲LH分泌沿着大量其他激素和代谢底物，以阐明LH分泌初始刺激的急性事件（Clarke实验室，澳大利亚）。 来自两个不同分类群的物种的比较将检验结论的普遍性。

DESCRIPTION (provided by applicant): This multidisciplinary, international collaboration will broaden our understanding of infertility and related complications (e.g., osteoporosis) due to undernutrition, dieting, excessive exercise, anorexia nervosa, obesity and diabetes. The hypothalamic-pituitary-gonadal (HPG) system is dependent upon the availability of metabolic fuels, but the location and nature of the metabolic stimuli are unknown. Food restriction (FR) inhibits estrous cycles and pulsatile secretion of luteinizing hormone (LH), and these effects are reversed within hours after refeeding. FR leads to changes in a staggeringly long list of hormones, neuropeptides and metabolic events. The rapid effects of refeeding will allow us to pinpoint those neuroendocrine events that occur rapidly enough to account for the effects of refeeding, and to discount slower changes that serve functions other than reproduction. Radioimmunoassy, immunocytochemistry, in situ hybridization and pushpull perfusion will be used to measure circulating hormones (insulin, leptin, growth hormone, ghrelin) and brain neuropeptides (e.g., neuropeptide Y and corticotropin releasing hormone) in hamsters and sheep that have been either fed ad libitum, FR, or FR and then refed. In addition, FR hamsters and sheep will be refed with various macronutrients and fuels to determine the metabolic stimuli that are critical for rapid restoration of HPG function. The hamster's consistent, easily monitored four-day estrous cycle enables rapid progress in elucidating certain basic requirements for estrous cyclicity (Schneider laboratory, USA). The larger blood supply of the ewe will allow us to measure pulsatile LH secretion along with a wide array of other hormones and metabolic substrates in order to elucidate the acute events that underlie the initial stimulation of LH secretion (Clarke laboratory, Australia). Comparisons of species from two different taxa will test the generality of the conclusions.