ROLE OF GLUCOCORTICOIDS IN THE MATURATION OF RENAL CORTICAL NA+ H+ EXCHANGER ACTIVITY DURING FETAL LIFE IN SHEEP/

We have studied the role of glucocorticoids in inducing the maturation in activity of the proximal tubule Na+/H+ exchanger that follows birt h. Renal cortical microvillus membrane vesicles were prepared from 132 -day gestation sheep fetuses (n = 8) that had received intraperitoneal cortisol (13 mu g . kg(-1). h(-1)) for the previous 48 h. Membrane ve sicles were also obtained from sham-operated twin controls (n = 8). Am iloride-sensitive uptake of Na-22(+) by these vesicles was measured, a nd Woolf-Augustinsson-Hofstee plots were used to determine the Michael is constant (K-m) and maximal velocity (V-max). There was no significa nt difference in K-m; however, the V-max was 61% higher in cortisol-tr eated fetuses. Posttreatment circulating cortisol levels were signific antly higher in the treated fetuses. Total RNA was collected from rena l cortex of the eight pairs of twins when killed. Renal cortex Na+/Hexchanger 3 (NHE3) mRNA levels were approximately fourfold higher in c ortisol-treated than in control fetuses. Although proximal tubule Na+/ H+ exchanger activity and renal cortex NHE3 mRNA levels increased sign ificantly in cortisol-treated fetuses, cortisol infusion did not stimu late renal sodium reabsorption in the fetus but rather produced a natr iuresis. These results demonstrate that glucocorticoids can induce an increase in both Na+/H+ exchanger activity and NHE3 mRNA levels during the last trimester of gestation in sheep. However, these changes are not associated with an increased ability of the fetal kidney to reabso rb sodium.