UTERINE METAB & BODY TEMP IN DECIDUALIZED PSEUDOPREG: DEX REPRODUCT THERAPY: RAT

子宫代谢检查

• 批准号: 6122958
• 负责人: FITZGERALD SPENCER
• 金额: $ 9.16万
• 依托单位: SOUTHERN UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6122958
• 关键词: Mammalia; biomaterials; carbohydrates; clinical research; drug /agent; endocrine gland /system; hormones; minority institution research support; proteins; reproductive system; surgery; women's health

The mechanism whereby the glucocorticoids can promote resistance to the stimulatory effects of growth factors in target tissues remain unknown and generally confined to uncertainty. In this regard, studies conducted by Rabin et al., 1990 have indicated that such mechanisms may function by the production of intracellular proteins which regulate the steps involved in signal transduction form the growth factor receptors. Hence the specific aim of the project will be to investigate whether there are possible broad avenues through which the synthetic glucocorticoid (DEX) could be involved in the inhibition of cellular and biological functions during reproduction. The proposed investigation will incorporate two aspects: 1. the more specific uterine metabolism during decidualized pseudopregnancy (DCPG); and 2. the more general body temperature rhythm during this reproductive tenure. While employing the albino rat as a mammalian model, the studies will be focused on the post-implantational period (Days 5-12 DCPG) which is critical for embryonic development and fetal organogenesis. Also the time-dependent administration of DEX will also be studied. This will help to clarify the circadian effectiveness of the treatment. Consequently, the hypotheses to be tested are as follows: Firstly, whether DEX, a synthetic glucocorticoid, can adversely influence DCPG (a possible anti-deciduogenic action). This will be accomplished by studying the growth of the decidualized uterus following its stimulation on Day 4 DCPG. In this regard the levels of uterine protein and glycogen will be employed as endpoints for the possible antagonistic activity of DEX on uterine growth. Uterine progesterone content, plus cytosolic and nuclear progesterone and estrogen receptor measurements should shed some light on uptake/receptor interactive involvement. Secondly, whether DEX can negatively interrupt the more general body temperature function during DCPG will also be ascertained. The endpoints to be tested whether the time-related treatment (a possible chronotoxic effect) with DEX is of any importance in biological responsiveness and/or sensitivity will constitute a point which will also be tested.

糖皮质激素促进耐药性的机制 对靶组织中生长因子的刺激作用尚存 未知的，通常局限于不确定性。在这方面， 拉宾等人于1990年进行的研究表明， 机制可能是通过产生细胞内蛋白来发挥作用。 它们调节信号转导过程中涉及的步骤 生长因子受体。因此，该项目的具体目标将是 是要调查是否有可能通过 其中合成的糖皮质激素(DEX)可能参与了 在生殖过程中抑制细胞和生物功能。 拟议的调查将包括两个方面：1.更多 蜕膜化假孕特殊的子宫代谢 (DCPG)；以及2.在此期间更普遍的体温节律 生育终身制。同时利用白化大鼠作为哺乳动物 模型，研究将集中在种植后阶段。 (DCPG 5-12天)，这对胚胎发育和胎儿 器官发生。此外，依赖时间的DEX管理也将 也有待研究。这将有助于澄清昼夜节律 治疗效果。 因此，需要检验的假设如下：第一， 地塞米松，一种合成的糖皮质激素，是否会对DCPG产生不利影响 (可能是一种抗蜕膜生成的行动)。这将通过以下方式实现 对蜕膜化子宫发育的研究 DCPG第4天的刺激。在这方面，子宫的水平 蛋白质和糖原将被用作可能的 地塞米松对子宫生长的拮抗作用。子宫孕酮 含量，外加胞浆和胞核的孕酮和雌激素受体 测量应该有助于了解摄取/受体的相互作用 参与其中。其次，DEX是否可以负面地干扰更多 DCPG期间的一般体温功能也将 已经确定了。要测试的端点是否与时间相关 地塞米松的治疗(一种可能的时间毒性效应)是 生物响应性和/或敏感性的重要性将 这一点也将受到考验。