Abstract
OBJECTIVES: The aim of this study was to investigate the effect of cortisol on growth-related genes in the ovine placenta. STUDY DESIGN: Ewes carrying singleton pregnancies were operated on between 112 and 116 days of gestation (115 ± 0.4, term = 147 days) and randomly assigned into three groups: six control animals, five ewes that were administered cortisol by continuous intravenous infusion (1 mg/kg/day, high cortisol), and five ewes that were adrenalectomized and replaced with 0.5-0.6 mg cortisol/kg/day and 3 μg aldosterone/kg/day to produce cortisol concentrations equivalent to pre-pregnancy values (low cortisol). At necropsy (130 ± 0.2 days of gestation), placental tissue was frozen and stored at -80 °C for mRNA analysis. MAIN OUTCOME MEASURES: To assess potential molecular mechanisms by which cortisol alters placental structure and function and fetal growth. RESULTS: Cortisol levels did not significantly affect 11β-hydroxysteroid dehydrogenase 1 and 2 enzymes, glucocorticoid receptor, mineralocorticoid receptor and angiotensin II receptor, type 1 (AT1R) expression levels. Gene expression levels of AT2R were increased in the high cortisol group for type B placentomes. There was little effect of cortisol on the insulin-like growth factor (IGF) axis. There was significantly more IGF-I mRNA in B versus A type and more IGFBP-2 mRNA in B and C type versus A type placentomes regardless of treatment (p < 0.05). CONCLUSIONS: These data suggest that cortisol increases placental AT2R expression at high concentrations whereas it has little effect on the placental IGF axis.