Adrenocorticoid regulation of Na+, K+-ATPase in adult rat kidney: effects on post-translational processing and mRNA abundance

The mechanisms by which adreno-corticoid hormones regulate Na⁺, K⁺-ATPase in adult kidney were studied in adrenalectomized (Adx) rats. Five days after adrenalectomy, Na⁺, K⁺-ATPase activity was significantly reduced in the renal cortex homogenate (C = 13.0±0.8 vs. Adx = 7.1±0.7 μmol Pi mg^-1 protein h^-1) and in renal microsomes (C = 30.3 ± 1.9 vs Adx = 14.6 ± 1.3 μmol Pi mg^-1 protein h^-1). Glucocorticoid replacement treatment of adrenalectomized rats with betamethasone (20 μg kg^-1 body wt twice daily for 5 days) effectively counteracted the observed reduction in Na⁺, K⁺-ATPase activity. In cortical homogenate the protein level of α1 and β1 subunits measured in immunoblots was not significantly different in Adx and control rats, indicating that 5 days after adrenalectomy the α1 and β1 subunits were present in renal cortical cells to almost normal extent but could not be assembled into a transmembrane functional unit. In support of this conclusion we found that the protein level of both the α1 and β1 subunits was significantly lower (P < 0.001 for both subunits) in microsomes from Adx than in control rats. The mRNA abundance for α1 and β1 subunits were not lower in Adx as compared to control rats 1 and 5 days after surgery. However, if Adx rats were given a single dose of betamethasone (600 μg kg^-1 body wt), a significant 2-fold increase in both α1 and β1 mRNAs was observed (P < 0.05 for both subunits). These data suggest that glucocorticoids can upregulate the mRNA of both Na⁺, K⁺-ATPase subunits but that the low renal Na⁺, K⁺-ATPase activity in adult Adx rats is mainly due to loss of glucocorticoid regulation of the post-translational processing of the enzyme.