REGULATION OF OVARIAN FOLLICULAR STEROID PRODUCTION

在卵泡期，排卵前卵泡的能力 产生雄激素和雌二醇大大增加，而黄体酮 分泌量仍然很低。在体内，促黄体生成素/卵泡刺激素激增触发了几个 巨大而重要的变化，包括卵泡/黄体期 类固醇合成的转变。在这一转变过程中，卵泡产生 雌二醇和雄激素水平显著下降，卵泡膜和颗粒细胞 转变为主要生产黄体酮-即转变为 卵泡细胞向黄体细胞转化是启动的。尽管关键的是 卵泡发育的这一阶段对成功的重要性 繁殖，人们对其繁殖机制知之甚少。 卵泡/黄体时相转移完成，可能是因为 变化太快了。催产素(OT)是由卵巢颗粒细胞分泌的。 人类和包括牛在内的许多其他哺乳动物物种。 在当前资助期内进行的实验表明， 黄牛催产素参与了黄体生成素高峰诱导 黄体形成的初始阶段。牛作为一种动物具有独特的优势 一种研究卵泡/黄体时移调节的模型 哺乳动物是因为：它们可以在实验中被诱导开始黄体 退化和新的卵泡期；大量的颗粒和 卵泡膜细胞可以从单个卵泡中获得； 发情可作为黄体生成素/卵泡刺激素高峰时间的标志。因此 牛将被用来确定卵泡/黄体的机制 相移，以深入了解这一重要的发展 过渡，并探讨拟议的新型监管机构OT的作用。 目的1确定促性腺激素与催产素的关系。 增加牛颗粒细胞孕酮的分泌，以测试 假设至少有一部分机制是通过 促性腺激素“黄素化”颗粒细胞是通过增加催产素 制作。目标2是确定黄体素是如何在 Ot和Ot基因在体内和体外的表达 特定的类固醇生成酶。目标3中的实验将集中在 体外自发黄体生成机制的研究 促性腺激素和催产素在体外使细胞“黄体化”。在目标4中， 雌二醇作为黄体化的调节剂将被评估。这个 令人振奋的滤泡微透析新技术将在AIM中使用 5检验有关促黄体生成素和催产素在 体内卵泡/黄体时相转移。 总之，这些实验将为监管提供新的见解 在卵泡发育的这个过渡阶段是如此关键 为了生育。

During the follicular phase the capacity of preovulatory follicles to produce androgens and estradiol increases greatly, whereas progesterone secretion remains low. In vivo the LH/FSH surge triggers several dramatic and important changes, including the follicular/luteal phase shift in steroidogenesis. During this transition, follicular production of estradiol and androgen decrease greatly and theca and granulosa cells shift to primarily progesterone production - i.e., the transformation of follicle cells to luteal cells is initiated. Despite the critical importance of this phase of follicular development to successful reproduction, little is known about the mechanisms by which the follicular/luteal phase shift is accomplished, perhaps because the changes are so rapid. Oxytocin (OT) is produced by granulosa cells from humans and a number of other mammalian species, including cattle. Experiments conducted during the current grant period suggest that in cattle OT is involved in the mechanism by which the LH surge induces the initial stages of luteinization. Cattle offer unique advantages as a model for studying regulation of the follicular/luteal phase shift in mammals because: they can be induced experimentally to initiate luteal regression and a new follicular phase; large numbers of granulosa and theca cells can be obtained from a single follicle; and behavioral estrus serves as marker for the time of the LH/FSH surge. Therefore cattle will be used to determine mechanisms of the follicular/luteal phase shift, to gain insight into this important developmental transition and to explore the role of a proposed novel regulator, OT. Aim 1 is to determine the relationship between gonadotropins and OT in increasing progesterone secretion by bovine granulosa cells, to test the hypothesis that at least part of the mechanism by which the gonadotropins "luteinize" granulosa cells is via an increase in OT production. Aim 2 is to determine how luteinization is accomplished in vivo and in vitro in terms of expression of the genes for OT and specific steroidogenic enzymes. Experiments in Aim 3 will be focused on spontaneous luteinization iv vitro to examine mechanisms by which gonadotropins and OT "luteinize" cells in vitro. In Aim 4 the role of estradiol as a regulator of luteinization will be evaluated. The exciting new technique of follicular microdialysis will be used in Aim 5 to test hypotheses about the roles of LH and OT in the follicular/luteal phase shift in vivo. Together these experiments will provide new insight into the regulation of this transitional stage in follicular development that is so critical for fertility.