Rogers S A, Miller S B, Hammerman M R
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Am J Physiol. 1990 Sep;259(3 Pt 2):F474-9. doi: 10.1152/ajprenal.1990.259.3.F474.
To determine whether growth hormone (GH) directly stimulates insulin-like growth factor I (IGF I) gene expression in renal collecting duct, plasma membranes prepared from collecting ducts isolated from rat kidney, and collecting ducts themselves were incubated in presence and absence of GH. GH enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for GH-signal transduction. Inclusion of GH in suspensions of collecting ducts increased production of immunoreactive IGF I in a time-dependent and concentration-dependent manner. Production was stimulated significantly by addition of 10(-10), 10(-8), or 10(-6) M GH to suspensions for 2 h. IGF I produced in isolated collecting ducts was released into the suspending media. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M GH in vitro. IGF I of collecting duct origin was indistinguishable from recombinant human IGF I in terms of its size and receptor-binding characteristics. Our findings demonstrate a direct action of GH to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect the mechanism by which GH stimulates renal IGF I production in intact kidney.
为了确定生长激素（GH）是否直接刺激肾集合管中胰岛素样生长因子I（IGF I）的基因表达，将从大鼠肾脏分离的集合管制备的质膜以及集合管本身分别在有和没有GH的情况下进行孵育。GH增强了集合管质膜中的磷脂酶C活性，确立了GH信号转导的可能性。在集合管悬浮液中加入GH，以时间和浓度依赖的方式增加了免疫反应性IGF I的产生。向悬浮液中加入10^(-10)、10^(-8)或10^(-6) M GH 2小时，可显著刺激其产生。在分离的集合管中产生的IGF I被释放到悬浮培养基中。在体外与10^(-6) M GH孵育后，集合管中IGF I mRNA的水平增加了2.8倍。就其大小和受体结合特性而言，集合管来源的IGF I与重组人IGF I无法区分。我们的研究结果表明，GH在体外具有直接增强集合管IGF I基因表达的作用。这种增强作用可能反映了GH在完整肾脏中刺激肾IGF I产生的机制。
