Altered physiology resulting in large follicular cysts.

生理学改变导致大的卵泡囊肿。

• 批准号: 6788111
• 负责人: MILO C WILTBANK
• 金额: $ 7.28万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-06 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6788111
• 关键词: corpus luteum; cow; estradiol; gonadotropin releasing factor; graafian follicles; hormone metabolism; hormone regulation /control mechanism; luteinizing hormone; physiology; reproduction; reproductive system disorder

DESCRIPTION (provided by applicant): The development of follicular cysts has been detected in numerous mammalian species, including humans, suggesting that this reproductive abnormality may be due to an underlying physiological pathway that is fairly ubiquitous in mammals. The research in this proposal focuses on the physiology that underlies the development of large follicular cysts. The cow has been chosen as the animal model for studies of this abnormality because follicular cysts are fairly common in this species and have been extensively described in previous research. In addition, the cow is a mono-ovulatory species and has been a useful animal model for understanding follicular development particularly because key follicular events (follicular selection, ovulation) occur at similar follicular diameters in humans and cows. The studies in this proposal test a working model based on previous scientific research, as well as our recent studies on the physiology that underlies the development of follicular cysts. This model predicts that during each estrous cycle, the normal estradiol surge induces a physiological condition that resembles the condition that results in follicular cysts. However, this "physiological lesion" is removed by the increase in circulating progesterone following ovulation. This model is very appealing because it provides a generalized physiological explanation for the development of large follicular cysts. It may also provide an explanation for the varied clinical, environmental, and experimental situations that result in the development of follicular cysts as well as provide a rationale basis for the treatment of this disorder. However, it is prudent to test whether this physiological model has experimental validity prior to extensive studies on the specific cellular and molecular mechanisms that underlie this disorder or extrapolation of this working model into species other than the cow. Therefore, we propose two specific objectives that will use the bovine animal model to test whether a normal endogenous estradiol surge will result in the postulated physiological condition. Specific Objective I. Determine whether follicular cysts will develop following an endogenous estradiol and GnRH surge if the LH surge is blocked with a GnRH antagonist. Specific Objective II. Determine whether follicular cysts will develop following an endogenous estradiol, GnRH, and LH surge if the freshly ovulated follicle (corpus hemmoragicum) is removed.

描述（由申请人提供）：在包括人类在内的许多哺乳动物物种中都检测到卵泡囊肿的发育，这表明这种生殖异常可能是由于哺乳动物中普遍存在的潜在生理途径。本提案的研究重点是大滤泡囊肿发展的生理学基础。奶牛被选择作为研究这种异常的动物模型，因为卵泡囊肿在这种物种中相当常见，并且在以前的研究中已被广泛描述。此外，奶牛是单排卵物种，是了解卵泡发育的有用动物模型，特别是因为人类和奶牛的关键卵泡事件（卵泡选择、排卵）发生在相似的卵泡直径上。本提案中的研究基于以往的科学研究，以及我们最近对卵泡囊肿发展的生理学研究，测试了一个工作模型。该模型预测，在每个发情周期中，正常雌二醇的激增会引发一种类似于导致卵泡囊肿的生理状况。然而，这种“生理损伤”被排卵后循环黄体酮的增加所消除。这个模型非常有吸引力，因为它为大滤泡囊肿的发展提供了一个广义的生理解释。它还可以解释导致卵泡囊肿发展的各种临床、环境和实验情况，并为这种疾病的治疗提供理论基础。然而，在对这种疾病背后的特定细胞和分子机制进行广泛研究或将这种工作模型外推到奶牛以外的物种之前，测试这种生理模型是否具有实验有效性是谨慎的。因此，我们提出了两个具体的目标，即使用牛动物模型来测试正常的内源性雌二醇激增是否会导致假设的生理状况。具体目的1 .确定内源性雌二醇和GnRH激增后，如果使用GnRH拮抗剂阻断LH激增，是否会发生卵泡囊肿。具体目标如果刚排卵的卵泡（血库）被切除，确定是否会在内源性雌二醇、GnRH和LH激增后发展卵泡囊肿。