REGULATION OF OVARIAN FOLLICULAR ESTRADIOL PRODUCTION

本提案的目的是确定下列因素和条件： 调节卵泡中雌二醇的合成。 埃克塞特是 排卵前卵泡发育的主要类固醇产物， 雌二醇分泌是卵泡达到排卵状态所必需的。 最近在几个物种中的调查导致了两个物种的形成。 细胞，两种促性腺激素调节雌二醇产生的模型。 根据这个模型，LH刺激卵泡膜细胞产生雄激素， FSH刺激颗粒细胞将雄激素芳香化为雌激素。 这 该提案旨在进一步研究 促性腺激素和卵泡细胞之间的相互作用， 促进卵泡雄激素和雌激素产生的颗粒细胞。 具体地说，我们将确定何时以及为什么LH和FSH是必不可少的， 通过体外和体内实验相结合的方式发育卵泡。 卵泡不同阶段分离的卵泡膜细胞和颗粒细胞 开发将在体外测试类固醇生成能力， 对LH和/或FSH的反应和牛卵泡将被剥夺LH或 在发情周期的特定时间内体内FSH刺激。 因为它 据信在体内促性腺激素从垂体释放， 脉冲，第二个和相关的问题，将解决的是效果 LH脉冲对离体牛卵泡膜和颗粒类固醇合成的影响 细胞和体外灌注的整个牛卵巢。 第三，我们将测试 雌二醇合成的雄激素前体是 通过Delta 5途径合成。 来自大鼠和奶牛的卵泡膜细胞将被 与外源性雄激素前体和抑制剂 类固醇生成酶和对雄激素产生的影响将是 评估。 最后，研究了牛的类固醇合成能力， 囊性卵泡将继续通过实验，其中囊肿将 通过实验诱导，并评估其类固醇生成能力， 体外 拟议的实验将提供一个更好的理解 激素控制卵泡发育，因此，可能最终导致 开发更好的诱导排卵和治疗方法 不孕

The objective of this proposal is to identify factors and conditions that regulate estradiol synthesis in ovarian follicles. Estradiol is the dominant steroid product of developing preovulatory follicles and continued estradiol secretion is essential for follicles to reach ovulatory status. Recent investigations in several species have led to formulation of a two cell, two gonadotropin model of the regulation of estradiol production. According to this model, LH stimulates theca cells to produce androgen and FSH stimulates granulosa cells to aromatize androgen to estradiol. This proposal is designed to investigate further interactions between gonadotropins and follicle cells and interactions between theca and granulosa cells that promote follicular androgen and estrogen production. Specifically, we will determine when and why LH and FSH are essential for developing follicles by a combination of experiments in vitro and in vivo. Theca and granulosa cells isolated at different stages of follicular development will be tested in vitro for steroidogenic capabilities and responses to LH and/or FSH and bovine follicles will be deprived of LH or FSH stimulation in vivo at specific times of the estrous cycle. Since it is believed that in vivo gonadotropins are released from the pituitary in pulses, a second and related question that will be addressed is the effect of pulses of LH on steroidogenesis by isolated bovine theca and granulosa cells and by whole bovine ovaries perfused in vitro. Third, we will test the hypothesis that the androgen precursor for estradiol synthesis is synthesized via the Delta5 pathway. Theca cells from rats and cows will be cultured with exogenous androgen precursors and with inhibitors of steroidogenic enzymes and the effects on androgen production will be assessed. Finally, studies on the steroidogenic capabilities of bovine cystic follicles will be continued through experiments in which cysts will be induced experimentally and their steroidogenic capabilities assessed in vitro. The proposed experiments will provide a better understanding of the hormonal control of follicular development and thus, may eventually lead to the development of better methods of inducing ovulation and treating infertility.