Thyroid hormone upregulates Na,K-ATPase α and β mRNA in primary cultures of proximal tubule cells

In vivo studies have demonstrated that thyroid hormone regulates the activity of Na,K-ATPase in the mammalian kidney. However, it is still unclear whether upregulation of Na,K-ATPase by thyroid hormone is mediated through the direct action on renal tubule cells or through other mediators, such as an increase in glomerular filtration rate. Using primary cultures of rabbit renal proximal tubule cells, studies were undertaken to elucidate this problem. We found that Na,K-ATPase activity was increased by 26 ± 8%, 30 ± 9%, 39 ± 9% after 24-h treatment with T₃ of 10^-11, 10^-9, 10^-a7 M, respectively. We further demonstrated that 24-h incubation of T₃ (10^-7 M) enhanced α- and β-protein abundance by 44 ± 29% and 31 ± 16%, and α- and β-mRNA levels by 84 ± 27% and 65 ± 11%, respectively. The time course studies revealed that the significant increase in Na,K-ATPase activity, α- and β-protein and mRNA abundance didn't appear until 24-h of T₃ treatment. Our data indicate that thyroid hormone directly upregulates Na,K-ATPase in proximal tubule cells via a pretranslational mechanism.