Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function

描述(由申请人提供)：科罗拉多大学安舒茨医学院性别差异研究专业中心(UCAMC SCOR)的首要目标是开发一个跨学科和翻译研究计划，以促进对性腺功能丧失的生物能量和新陈代谢后果的理解。从对实验室动物的研究中有令人信服的证据表明，性腺切除会导致男性和女性的自发体力活动急剧减少30%-80%。更耐人寻味的是，观察到这会导致雌性动物体重增加，内脏脂肪显著增加，并导致代谢障碍，但雄性动物不会。如果这些发现与人类相关，那么与年龄相关的性腺功能下降可能是疾病风险的一个重要独立决定因素。此外，预计这将对女性的健康产生比男性更大的不利影响，因为女性的性腺功能丧失发生在较早的年龄。将有三个SCOR研究项目推进这一领域的新研究：1)项目I(临床)：妇女卵巢功能丧失的生物能量和代谢后果(PI：W Kohrt)；2)项目II(临床前)：既往肥胖对卵巢功能丧失后果的影响(PI：P MacLean)；以及3)项目III(基础)：性激素以不同方式调节不同脂肪细胞群体的产生(PI：D Klemm)。行政核心将通过以下方式为SCOR的成功做出贡献：1)为关于性腺功能丧失的后果的重点转化性和跨学科研究计划提供科学领导；2)监测SCOR研究项目的生产力；3)通过辅助项目计划扩大SCOR的范围；4)通过辅助项目计划扩大研究人员队伍，研究性腺对能量平衡和新陈代谢的调节；5)将SCOR的活动与UCAMC的密切合作项目结合起来，包括老龄中心、BIRCWH、妇女健康研究中心、营养和肥胖研究中心、妇女生殖健康研究职业发展方案以及科罗拉多州临床和翻译科学研究所；6)提供生物统计和数据 为特别委员会的研究项目提供管理支持；以及7)为特别委员会活动的财务监督、监管监督以及时间安排和一般管理提供行政支助。 公共卫生相关性：SCOR与两个必需的总体主题密切相关：1)所有3个项目都涉及性别/性别决定因素，因为它们调查了影响健康的性腺功能丧失的生物学影响；以及2)SCOR是跨学科的，因为 通过对小鼠脂肪细胞谱系的调节的关注(项目III)，证明了 局部雌激素产生对大鼠脂肪和肌肉代谢的影响(项目二)，到性腺功能丧失对女性身体活动和能量平衡的影响(项目一)。

DESCRIPTION (provided by applicant): The overarching objective of the University Of Colorado Anschutz Medical Campus Specialized Center Of Research on Sex Differences (UCAMC SCOR) is to develop an interdisciplinary and translational research program to advance the understanding of the Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function. There is compelling evidence from studies of laboratory animals that gonadectomy causes a dramatic decrease of 30-80% in spontaneous physical activity in males and females. Even more intriguing is the observation that this results in excess weight gain, a marked increase in visceral fat, and metabolic dysfunction in female animals but not males. If such findings are relevant to humans, the age related decline in gonadal function may be an important independent determinant of disease risk. Moreover, this would be expected to have a greater adverse effect on the health of women than men, because the loss of gonadal function occurs at an earlier age in women. There will be three SCOR Research Projects to advance novel research in this area: 1) Project I (clinical): Bioenergetic and Metabolic Consequences of the Loss of Ovarian Function in Women (PI: W Kohrt); 2) Project II (preclinical): Effects of Pre-existing Obesity on Consequences of the Loss of Ovarian Function (PI: P MacLean); and 3) Project III (basic): Sex Hormones Differentially Regulate Production of Distinct Adipocyte Populations (PI: D Klemm). The Administrative Core will contribute to the success of the SCOR by: 1) providing scientific leadership for a focused translational and transdisciplinary research program on the consequences of the loss of gonadal function; 2) monitoring the productivity of SCOR Research Projects; 3) expanding the scope of the SCOR through an Ancillary Projects program; 4) expanding the cadre of investigators conducting research on the gonadal regulation of energy balance and metabolism through the Ancillary Projects program; 5) integrating activities of the SCOR with closely partnered programs at UCAMC, including the Center on Aging, the BIRCWH, the Center for Women's Health Research, the Nutrition and Obesity Research Center, the Women's Reproductive Health Research Career Development program, and the Colorado Clinical and Translational Science Institute; 6) providing biostatistical and data management support for the SCOR research projects; and 7) providing administrative support for financial oversight, regulatory oversight, and scheduling and general management of SCOR activities. PUBLIC HEALTH RELEVANCE: The SCOR is closely aligned with the 2 required overarching themes: 1) all 3 projects address sex/gender determinants because they investigate biological effects of the loss of gonadal function that impact heath; and 2) the SCOR is interdisciplinary, as evidenced by the focus on the regulation of the lineage of adipocytes in mice (Project III), to the impact of local estradiol production on fat and muscle metabolism in rats (Project II), to the effect of the loss of gonadal function on physical activity and energy balance in women (Project I).