The Primate Corpus Luteum: Functional Regression and Cardiovascular Impacts

灵长类动物黄体：功能退化和心血管影响

• 批准号: 8549776
• 负责人: Randy L Bogan
• 金额: $ 16.31万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549776
• 关键词: Address; Affect; Aging; Blood specimen; Cardiovascular Diseases; Cardiovascular system; Cell Culture Techniques; Cholesterol; Contraceptive Agents; Coronary heart disease; Diabetes Mellitus; Estradiol; Future; Gene Expression; Gene Targeting; Heart Diseases; Hormonal Oral Contraceptives; Hormones; Hour; Injection of therapeutic agent; Instruction; Intervention; Lipids; Lipoprotein Receptor; Lipoproteins; Liver; Longevity; Luteal Phase; Luteolysis; Mediating; Menopause; Menstrual cycle; Modeling; Molecular; Obesity; Ovarian; Ovary; Phase; Physiological; Placebos; Pregnancy; Pregnancy loss; Premenopause; Primates; Progesterone; Prostaglandins; Protein Isoforms; Reproductive Process; Research; Risk; Risk Factors; Sheep; Steroids; Testing; Tissues; Woman; assisted reproduction; cardiovascular disorder risk; corpus luteum; extracellular; heart disease risk; improved; lipoprotein triglyceride; novel; prevent; receptor; receptor-mediated signaling; reverse cholesterol transport; uptake

PROJECT SUMMARY (See InstnjcUons): The long-term objectives of this application are to understand and reduce the large numbers of pregnancies that are lost because of inappropriate regression of the primate corpus luteum (CL) at the end of the menstrual cycle, and to contribute to better management of cardiovascular disease (CVD) risk in wromen by determining how reproductive processes influence CVD risk factors. The research plan will address the novel hypothesis that cholesterol uptake and efflux activities, regulated by liver x receptor (LXR) a and/or p,determine luteal steroidogenic lifespan and reduce the risk of developing CVD. To test this hypothesis, the first aim will determine whether LXR signaling mediates prostaglandin F2a (PGF2a)-induced luteolysis in non-primate species. Sheep will receive either placebo or PGF2a during the mid-luteal phase with serial blood samples collected to verify reduced progesterone (P4) levels indicative of luteolysis. Corpora lutea will be collected at 12, 24, or 48 hours after injection and expression of known LXR target genes and lipoprotein receptors will be determined, as well as differences in cholesterol efflux and extracellular lipoprotein uptake in cell cultures derived from freshly isolated tissue. This will test the hypothesis that the LXRs mediate PGF2a-induced luteolysis, and will determine the utility of a PGF2a-induced luteolytic model for future studies on the functional importance of the LXRs in luteal function. The second specific aim will differentiate direct ovarian contributions from systemic estradiol (E2) and P4 effects on circulating lipids during the normal menstrual cycle and hormonal oral contraceptive cycles. Circulating lipid levels will be determined in healthy, premenopausal women during their normal menstrual cycle, after having ovarian activity temporarily stopped to mimic menopause, while receiving E2 and P4 replacement during induced menopause, and during a monophasic combined hormonal oral contraceptive cycle. This aim will better our understanding of the mechanisms underlying premenopausal protection from heart disease and guide future studies to determine how physiologic conditions (e.g. aging, obesity, diabetes) and pharmacologic interventions (e.g. contraceptives) affect these premenopausal protective factors.

项目总结（见InstnjcUons）：