Role of glucocorticoids in the maturation of renal cortical Na⁺-K⁺- ATPase during fetal life in sheep

Glucocorticoid levels increase greatly at the time of birth in humans and sheep, coinciding with an increased ability of the kidney to reabsorb sodium. Cortisol induces proximal tubule apical membrane Na⁺/H⁺ exchanger maturation in near-term fetal sheep. Proximal tubule salt transport is ultimately-dependent on Na⁺ pump activity, so we studied the effects of cortisol treatment on renal cortical Na⁺-K⁺-ATPase. We first looked at six 140 day gestation fetal sheep (term is 145) and compared their renal cortical Na⁺-K⁺-ATPase to that of six 1-day-old lambs. Na⁺-K⁺-ATPase activity increased 80% after birth. Then nine pairs of twin fetal sheep were chronically instrumented at 127 days gestation. After 72 h recovery, one twin was given a 48-h continuous intraperitoneal infusion of cortisol. Both twins were then killed, and their renal cortices were studied. Na⁺-K⁺-ATPase activity increased 122% with cortisol treatment; activity equaled that of 1- day-old lambs. Protein abundance of the α₁-subunit of the Na⁺-K⁺-ATPase increased 19%; the α₁-subunit increased 39% with cortisol treatment, mRNA abundance of the α₁-subunit increased 58%; the β₁-subunit increased 72%. These results indicate that cortisol matures Na⁺-K⁺-ATPase activity.