MOLECULAR, CELLULAR & PHYSIOLOGICAL CONTROL OF RENAL FUNCTION DURING DEVELOPMENT

尿钠排泄量升高的机制 胎儿的生命和在早产儿中还没有被仔细地阐明。 最近的研究表明，不成熟的人能力的变化 肾脏对钠的重新吸收直接依赖于肾脏的发育 几种膜转运蛋白。研究的目的是 研究分子、细胞和生理机制 离子跨肾小管转运的发育调控 胎膜在胎儿期和从胎儿期向 新生儿的生命。更具体地说，我们提议测试将军 肾小管细胞发育分化假说 与功能和丰度的重要变化有关 膜蛋白起交换器、泵或通道作用的膜蛋白 允许离子在管状膜上的传输，并 确定影响胎儿生命周期内这些变化的因素 在从胎儿到新生儿的过渡过程中。为了测试这位将军 假设，目前的提议是为了a)阐明肾脏 Na/H交换器、Cl-/碱交换器和Na/K-ATPase的成熟 从胎儿到新生儿的过渡过程中的活动，并确定 Na/H交换器的成熟先于Na/K-ATPase的升高 从胎儿到新生儿过渡期间的活动；b)测试 假设糖皮质激素和甲状腺激素起重要作用 钠/氢交换器、氯离子/碱交换器在肾脏成熟中的作用 Na，K-ATPase活性在胎儿和出生后发育及 确定这两种激素是否具有协同作用。 管状离子转运；c)检验甲状腺切除术 阻止或延缓近端肾小管离子转运的出生后成熟； 以及d)检验这样的假设：早产羊的不敏感 胎儿近端小管对血管紧张素II的离子转运机制 继发于血管紧张素受体饱和。

The mechanisms responsible for the high urinary sodium excretion during fetal life and in pre-term infants have not been carefully elucidated. Recent studies have suggested that changes in the ability of the immature kidney to reabsorb sodium are directly dependent on the development of several membrane-transporting proteins. Studies are designed to investigate the molecular, cellular, and physiological mechanisms regulating the development of ion transport across the renal tubular membranes during fetal life and during the transition from fetal to newborn life. More specifically, we are proposing to test the general hypothesis that the developmental differentiation of renal tubular cells is associated with important changes in the function and abundance of membrane proteins that function as exchangers, pumps, or channels and allow for the transport of ions across the tubular membranes, and to determine the factors influencing these changes during fetal life and during the transition from fetal to newborn life. To test this general hypothesis, the present proposal is designed a) to elucidate the renal maturation of Na+/H+ exchanger, Cl-/base exchanger, and Na+/K+-ATPase activity during the transition from fetus to newborn, and to determine if the maturation of Na+/H+ exchanger precedes the rise in Na+/K+-ATPase activity during the transition from fetus to newborn; b) to test the hypothesis that glucocorticoids and thyroid hormones play an important role in the renal maturation of Na+/H+ exchanger, Cl-/base exchanger, and Na+,K+-ATPase activity during fetal and postnatal development and to determine if there is synergistic action of these two hormones on proximal tubular ion transport; c) to test the hypothesis that thyroidectomy prevents or delays postnatal maturation in proximal tubular ion transport; and d) to test the hypothesis that the insensitivity of the pre-term sheep fetus proximal tubule ion transport mechanisms to angiotensin II is secondary to saturation of angiotensin receptors.