Cortisol infusion decreases renin, but not PGHS-2, EP2, or Ep4 mRNA expression in the kidney of the fetal sheep at days 109-116

Renal prostaglandins (PG), renin, and cortisol are necessary for normal kidney development and function during fetal life. We examined the effects of cortisol infusion before completion of nephrogenesis (d 109-116 gestation; 2.0-3.0 mg hydrocortisone succinate/24 h) on the renal mRNA expression of PGHS-2, the PGE2 receptors, EP2 and EP4, and renin in fetal sheep. Cortisol infusion raised plasma cortisol levels to 42.8 +/- 6.0 nmol/L compared with saline infusion levels of 1.5 +/- 0.5 nmol/L (p < 0.001), but had no effect on fetal body weight, proportional kidney mass, or blood gases. Cortisol decreased significantly the relative expression of renin mRNA (saline: 0.93 +/- 0.06 units; cortisol: 0.32 +/- 0.03 units, p < 0.05), however it had no effect upon the expression of PGHS-2, EP2, or EP4 mRNA in fetal sheep kidney. Although there is substantial evidence that PGE2 acting through either the EP2 or EP4 receptor stimulates renin synthesis in the adult kidney, our results have demonstrated that before the completion of nephrogenesis, cortisol down-regulation of renin mRNA expression is independent of any change in the expression of PGHS-2, EP2, or EP4 mRNA expression. During nephrogenesis, the insensitivity of PGHS-2, EP2, and EP4 expression to down-regulation by cortisol may permit continued PG regulation of renal development and urine formation.Sarah J Williams, David M Olson, Dean B Zaragoza, Catherine L Coulter, Timothy G Butler, Jacob T Ross, and I Caroline Mcmille