Altered physiology resulting in large follicular cysts.

描述(申请人提供)：在包括人类在内的许多哺乳动物物种中都发现了卵泡囊的发育，这表明这种生殖异常可能是由于哺乳动物中相当普遍的潜在生理途径所致。这项建议中的研究重点放在大型滤泡囊肿发生的生理基础上。奶牛被选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，在以前的研究中已经得到了广泛的描述。此外，牛是单排卵物种，是了解卵泡发育的有用动物模型，特别是因为关键的卵泡事件(卵泡选择、排卵)在人类和奶牛的卵泡直径相似的情况下发生。这项建议中的研究测试了一个工作模型，该模型基于先前的科学研究，以及我们最近对毛囊囊肿发展基础上的生理学研究。该模型预测，在每个发情周期中，正常的雌二醇峰会导致一种类似于导致卵泡囊肿的生理状态。然而，这种“生理损伤”是通过排卵后循环孕酮的增加而消除的。这个模型非常吸引人，因为它为大卵泡囊肿的发展提供了一个普遍的生理学解释。它还可以解释导致卵泡囊肿发展的不同临床、环境和实验情况，并为这种疾病的治疗提供理论基础。然而，在广泛研究这种疾病背后的特定细胞和分子机制或将这种工作模式外推到奶牛以外的物种之前，谨慎的做法是测试这种生理模型是否具有实验有效性。因此，我们提出了两个具体的目标，将使用牛动物模型来测试正常的内源性雌二醇峰是否会导致假设的生理状况。具体目标I。如果用促性腺激素释放激素拮抗剂阻断促黄体生成素和促性腺激素释放激素的激增，确定内源性雌二醇和促性腺激素释放激素的激增是否会导致卵泡囊肿的形成。特定目标II。确定如果去除新鲜排卵的卵泡(血肿)，是否会在内源性雌二醇、促性腺激素释放激素和促黄体生成素激增后形成卵泡囊肿。

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.