Rogers S A, Miller S B, Hammerman M R
George M. O'Brien Kidney and Urological Disease Center, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Am J Physiol. 1995 Jan;268(1 Pt 2):F128-34. doi: 10.1152/ajprenal.1995.268.1.F128.
To define the role that thyroid hormones play in regulation of renal epidermal growth factor (EGF) production, we characterized the effect of triiodothyronine (T3) administration on renal EGF expression in adult rats. The action of T3 to regulate EGF production was examined under one condition in which renal EGF expression is known to be diminished, posthypophysectomy, and in pituitary-intact rats. Levels of mature EGF, EGF precursor, and EGF mRNA, reduced in kidneys of hypophysectomized rats compared with pituitary-intact animals, increased significantly following the administration of T3 to hypophysectomized rats. Thus replacement of thyroid hormone alone was sufficient to enhance renal EGF expression. Induction of a hyperthyroid state in normal rats by injection of T3 for 4 days increased levels of extractable immunoreactive mature EGF, EGF precursor present in renal membranes, and EGF mRNA measured in kidneys. Levels of EGF in circulation were undetectable under all experimental conditions. We conclude that T3 enhances the renal synthesis of EGF in both hypopituitary and pituitary-intact rats. Enhancement of renal EGF expression is one mechanism that must be considered to explain the actions of thyroid hormones on kidney.
为了确定甲状腺激素在调节肾脏表皮生长因子(EGF)产生中所起的作用,我们研究了在成年大鼠中给予三碘甲状腺原氨酸(T3)对肾脏EGF表达的影响。在垂体切除术后肾脏EGF表达已知会降低的一种情况下,以及在垂体完整的大鼠中,研究了T3调节EGF产生的作用。与垂体完整的动物相比,垂体切除的大鼠肾脏中成熟EGF、EGF前体和EGF mRNA的水平降低,而给予垂体切除的大鼠T3后这些水平显著升高。因此,单独补充甲状腺激素足以增强肾脏EGF的表达。通过注射T3 4天在正常大鼠中诱导甲状腺功能亢进状态,可增加可提取的免疫反应性成熟EGF、肾膜中存在的EGF前体以及肾脏中测量的EGF mRNA的水平。在所有实验条件下均未检测到循环中的EGF水平。我们得出结论,T3在垂体功能减退和垂体完整的大鼠中均增强肾脏EGF的合成。肾脏EGF表达的增强是解释甲状腺激素对肾脏作用时必须考虑的一种机制。