Role of cortisol in the ontogenic control of pulmonary and renal angiotensin-converting enzyme in fetal sheep near term.

1. This study examined the ontogeny of angiotensin-converting enzyme (ACE) concentration in the lungs and kidneys of fetal, newborn and adult sheep, and investigated the effects of cortisol infusion on tissue and plasma ACE in the chronically catheterised ovine fetus. 2. Pulmonary and renal ACE in utero increased from 113 days of gestation towards term; peak tissue ACE concentrations were observed in fetuses studied at 143 days (term, 145 +/- 2 days). The high level of ACE seen in the fetal lungs close to term was maintained in the lambs and adult ewes whereas renal ACE decreased immediately after birth and rose to a maximal value in the adult ewes. In all groups of animals studied, higher mean concentrations of ACE were observed in the kidneys than in the lungs. Ontogenic increments in pulmonary and renal ACE in utero were coincident with the prepartum cortisol surge. In untreated and saline-infused fetuses, plasma cortisol correlated with both pulmonary (r = 0.83, P < 0.0001) and renal (r = 0.53, P < 0.01) ACE concentrations, irrespective of gestational age. 3. An intravenous infusion of cortisol (2-3 mg kg-1 day-1) at either 113 or 129 days raised plasma cortisol to the level seen near term and caused an increase in pulmonary ACE at both gestational ages. Pulmonary ACE concentration in the cortisol-infused fetuses at 129 days, but not at 113 days, was similar to that observed in the fetuses near term. In contrast, cortisol infusion had no effect on renal ACE concentration at either 113 or 129 days of gestation. Plasma ACE concentration was also increased by exogenous cortisol at 129 days. 4. Therefore, these findings suggest that the ontogenic rise in ACE concentration observed in the lungs of the sheep fetus near term is induced, at least in part, by the prepartum cortisol surge.