Thyroid hormone upregulates gene expression, synthesis and release of pro-epidermal growth factor in adult rat kidney

Attempts were made to elucidate whether thyroid hormone upregulates renal proepidermal growth factor (pro-EGF) gene expression, biosynthesis and release in adult rats which were rendered hypothyroid. Predominantly pro-EGF was detected in renal cortex, whereas pro-EGF and its degraded species were found in urine. We demonstrated that T₃ increased pro-EGF levels in renal cortex to 2.2 ± 0.17, 2.37 ± 0.19, 2.73 ± 0.25, and 3.10 ± 0.45 fold within day 1, 2, 4 and 8, respectively following treatment. Immunoreactive EGF, assessed by immunohistochemical methods, was confined in the distal convoluted tubule and thick ascending limb of Henle. T₃ markedly enhanced the density of irEGF in these nephrons. T₃ augmented the concentration of urinary irEGF to 2.1, 2.2, 2.8 and 3.6 fold within day 1, 2, 4 and 8 and the abundance of urine pro-EGF to 2.53 ± 1.39, 3.8 ± 0.70, 3.59 ± 1.48 fold within day 1, 2, 4, respectively. Moreover, we employed reverse transcriptase/ polymerase chain reaction method to analyze relative abundance of pro-EGF mRNA in kidneys of various thyroid states and found T₃ markedly increased pro-EGF mRNA levels after treatment of 1, 2 and 4 days. These results indicated that thyroid hormone augmented the gene expression, biosynthesis and excretion of pro-EGF in adult rat kidney.