POLYAMINE REGULATION OF PROGESTERONE BIOSYNTHESIS

黄体是一个短暂的内分泌腺，在排卵部位形成于卵巢上。黄体合成和分泌类固醇激素孕酮是女性建立正常生殖周期和维持妊娠所必需的。我们有令人信服的数据表明，被称为多胺的脂肪族有机阳离子影响黄体分泌孕酮。多胺广泛存在于哺乳动物细胞中，参与多种细胞功能，包括细胞增殖、转录、翻译、激素受体-配体结合、第二信使水平和酶活性。除了多胺在正常细胞功能中的作用外，多胺代谢增加也与恶性细胞增殖有关。虽然多胺在正常和异常的细胞功能中起着关键作用，但它们在卵巢调节，特别是黄体类固醇合成中的作用还没有被评估。这项研究的总体目标是确定多胺在黄体孕酮合成和分泌中的作用。我们的近期目标是确定多胺是否1)影响类固醇合成酶的mRNA的积累，2)影响参与胆固醇运输的蛋白质的mRNA的积累，3)改变编码氧化应激反应酶的mRNA的水平，以及4)影响前列腺素F/2α信号转导通路。这些实验将提供有关控制卵巢内类固醇生成机制的细胞内机制的信息。通过进行这些实验，我们期望对了解多胺在卵巢类固醇生成中的作用做出重大贡献。通过利用分子方法进行体内和体外实验，我们相信这些目标将会实现，并为控制类固醇生成的卵巢机制提供新的见解。

The corpus luteum is a transient endocrine gland, which forms on the ovary at the site of ovulation. Synthesis and secretion of the steroid hormone, progesterone, by the corpus luteum is requisite for the establishment of normal reproductive cycles and maintenance of pregnancy in females. We have convincing data suggesting that the aliphatic organic cations known as polyamines, effect progesterone secretion by the corpus luteum. Polyamines are ubiquitously are ubiquitously distributed throughout mammalian cells where they are involved in a multitude of cellular functions include cell proliferation, transcription, translation, hormone receptor-ligand binding, second messenger levels and enzymatic activities. In addition to the roles of polyamines in normal cellular functions, increased polyamine metabolism is associated with malignant cell proliferation. Although polyamines play pivotal roles in normal and abnormal cellular function, their role in ovarian regulation, specifically corpus luteum steroidogenesis has not been evaluated. The overall goal of this investigation is to determine the role of polyamines in progesterone synthesis and secretion by the corpus luteum. Our immediate aims are to determine if polyamines 1) influence accumulation of mRNA for steroidogenic enzymes, 2) influence accumulation of mRNA for proteins involved in cholesterol transport, 3) alter levels of mRNA encoding oxidative stress response enzymes, and 4) effect prostaglandin F/2alpha signal transduction pathways. These experiments will provide information regarding intracellular mechanisms which govern steroidogenic mechanisms within the ovary. By conducting these experiments, we anticipate making significant contributions toward understanding the role of polyamines in ovarian steroidogenesis. By conducting both in vivo and in vitro experiments which utilizes molecular methodologies we are confident these aims will be accomplished and provide new insight into ovarian mechanisms that control steroidogenesis.