Components of the renin-angiotensin system have been found in a variety of tissues during fetal and postnatal life and appear to be developmentally regulated. We postulated that hormonal changes associated with parturition participate in the regulation of renin, angiotensinogen (Ao) and angiotensin type 1 receptor (AT1) gene expression. Cortisol, which increases rapidly in fetal blood before delivery, has been shown to influence the maturation of various systems in the developing fetus. To test the hypothesis that an increase in cortisol regulates fetal renin. Ao, and AT1 mRNA gene expression, we used Northern blot analysis to study the effects of an intraperitoneal infusion of cortisol (3 mg/h, 1 mL/h) for 48 h on the expression of these genes in twin ovine fetuses (n = 10 pairs) at 130-d gestation (term 145 d); one twin in each pair served as a saline-treated control (0.9% NaCl, 1 mL/h). Plasma cortisol levels were significantly higher in cortisol-treated fetuses (113 +/- 23 nmol/dL) than in twin controls (4.6 +/- 0.8 nmol/dL). Cortisol infusion significantly decreased AT1 receptor mRNA levels in kidney and liver by 24 +/- 7% and 27 +/- 8%, respectively, when compared with controls (p < 0.05), whereas in contrast, increased mRNA levels (p < 0.05) in heart right atrium (91 +/- 23%) and ventricle (59 +/- 20%). Renin mRNA levels decreased in renal cortex by 77 +/- 13% (p < 0.05) in cortisol-treated animals compared with controls. Hepatic Ao mRNA levels decreased by 15 +/- 5% in response to cortisol (p < 0.05), whereas no significant effect was seen on renal Ao gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)