Altered physiology resulting in large follicular cysts.

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检测到卵泡囊肿的发育，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所致。本提案中的研究重点是大滤泡囊肿发育的生理学基础。奶牛被选为研究这种异常的动物模型，因为卵泡囊肿在该物种中相当常见，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，并且一直是用于理解卵泡发育的有用动物模型，特别是因为关键卵泡事件（卵泡选择、排卵）在人类和奶牛中以相似的卵泡直径发生。本提案中的研究测试了基于先前科学研究的工作模型，以及我们最近对卵泡囊肿发展的生理学研究。该模型预测，在每个发情周期中，正常的雌二醇激增诱导类似于导致卵泡囊肿的条件的生理条件。然而，这种“生理性损伤”通过排卵后循环孕酮的增加而消除。这个模型是非常有吸引力的，因为它提供了一个广义的生理学解释大卵泡囊肿的发展。它还可以为导致卵泡囊肿发展的各种临床，环境和实验情况提供解释，并为治疗这种疾病提供理论基础。然而，在对这种疾病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，将使用牛动物模型，以测试是否正常的内源性雌二醇激增将导致假设的生理条件。具体目标一。确定如果LH峰被GnRH拮抗剂阻断，内源性雌二醇和GnRH峰后是否会发生卵泡囊肿。具体目标二。确定如果去除新鲜排卵的卵泡（出血体），内源性雌二醇、GnRH和LH峰后是否会发生卵泡囊肿。

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.