REGULATION OF OVARIAN FOLLICULAR STEROID PRODUCTION

描述：(改编自《摘要》)在卵泡期 排卵前卵泡产生雄激素和雌二醇的能力 大量增加，而孕酮分泌仍然很低。在活体内 促黄体生成素/卵泡刺激素激增引发了几个戏剧性和重要的变化，包括 类固醇生成中的卵泡/黄体时相从雄激素/雌二醇到 黄体酮/催产素。人们对这种转变的机制知之甚少。 牛作为研究卵泡/黄体的模型具有独特的优势 移位，因为排卵前卵泡可以在定义的 发育阶段，并提供大量的颗粒细胞和膜细胞 而行为性发情是促黄体生成素/促卵泡刺激素激增的标志。我们有 发现小范围极低剂量的促性腺激素(1-4 ng/ml) 培养的卵泡维持卵泡型激素的分泌 细胞，较高剂量可加速体外黄体化。我们建议 解决低(基本)浓度与高(激增)浓度的问题 相同的激素(促黄体生成素和卵泡刺激素)在 膜细胞和颗粒细胞。具体目标1将检验假设， 在卵泡期，卵泡细胞获得了 黄体化，使它们在体外可以保留卵泡细胞或 黄体生成，取决于提供的荷尔蒙环境。这将是 方法：1)确定是否维持低浓度的促黄体生成素或卵泡刺激素 卵泡型功能和高浓度促进黄体 PKA在牛卵泡膜细胞和颗粒细胞中的不同作用 Vs.PKC途径(具体目标2，3)，2)确定 类固醇生成酶、催产素和 STAR(类固醇生成急性调节蛋白)(特定目标4)。这个 内源性蛋白激酶C抑制物(PKCI)在细胞周期调控中的作用 还将检查卵泡细胞的黄体化(具体目标5)。

DESCRIPTION: (Adapted from Abstract) 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 from androgen/estradiol to progesterone/ oxytocin. Little is known about the mechanisms of this shift. Cattle offer unique advantages as a model for studying the follicular/luteal shift because preovulatory follicles can be obtained at defined developmental stages and provide large numbers of granulosa and theca cells and behavioral estrus serves as a marker for the LH/FSH surge. We have found that a narrow range of very low doses of gonadotropins (1-4 ng/ml) maintains follicular phase-type hormone secretion in cultured follicle cells, higher doses accelerate luteinization in vitro. We propose to address the question of how low (basal) vs. high (surge) concentrations of the same hormones (LH and FSH) elicit dramatically different responses in theca and granulosa cells. Specific Aim 1 will test the hypothesis that, during the follicular phase, follicle cells acquire the competence to luteinize such that in vitro they can retain functions of follicle cells or luteinize, depending on the hormonal milieu provided. This will be approached by : 1) determining if low concentrations of LH or FSH maintain follicular phase-type functions and high concentrations promote luteal functions in bovine theca and granulosa cells via differential use of PKA vs. PKC pathways (Specific Aims 2,3), 2) determining the role of differential expression of mRNA for steroidogenic enzymes, oxytocin, and StAR (steroidogenic acute regulatory protein) (Specific Aim 4). The potential role of an endogenous PKC inhibitor (PKCI) in regulation of luteinization of follicle cells will also be examined (Specific Aim 5).