Triiodothyronine stimulates renal epidermal growth factor expression in adult rat

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.