ABSTRACT. To determine whether expression of the hepatic angiotensinogen (Ao) gene is modulated by 1 ) ontogeny, 2) pregnancy, 3) glucocorticoids, or 4) triiodothyroxine (T3), time-dated pregnant Wistar-Kyoto rats were studied at different gestational ages (15, 17, and 20 d) without the influence of hormonal treatment or were given a daily intraperitoneal injection of dexamethasone (Dex) or T3 for 5 d (chronic Dex or T3) or a single injection of Dex (acute Dex). Maternal and fetal hepatic Ao mRNA levels were detected by dot and Northern blot analysis by using a full-length rat Ao cDNA. Fetal Ao mRNA levels were lower than in their maternal counterparts and lower than in adult rats of either sex. Maternal hepatic Ao mRNA levels were markedly diminished. mRNA levels were their lowest at 15 d of gestation and increased progressively as gestation advanced, reaching a peak at 20 d of gestation. Chronic Dex treatment resulted in a 190% increase in maternal and a 370% increase in the fetal hepatic Ao mRNA levels. Acute Dex treatment resulted in a 260% increase in maternal hepatic Ao mRNA levels with no change in the fetus. Hepatic Ao mRNA levels increased to the nonpregnant level with acute and chronic Dex treatment. Chronic T3 treatment resulted in a 20% increase in maternal hepatic Ao mRNA levels, without alteration of fetal Ao gene expression. We conclude that 1 ) the fetal and pregnant state results in a profound decrease in maternal and fetal hepatic Ao gene expression, 2) Ao gene expression is regulated by glucocorticoids in the term fetal and maternal liver, and 3) chronic T3 treatment results in a modest increase in maternal hepatic Ao gene expression. (Pediatr Res 30: 252-255,1991) Abbreviations Ao, angiotensinogen T3, L-triiodothyronine Dex, dexamethasone WKY, Wistar-Kyoto 32P, phosphorous 32All components of the circulating renin-angiotensin system are present in the adult, newborn, and maturing fetus (1-3). The prohormone Ao serves as substrate for the renin-angiotensin cascade and, as such, is the only known precursor of the vasoactive hormone angiotensin 11. We have recently demonstrated that angiotensinogen gene expression is developmentally regulated in a tissue-specific manner with hepatic angiotensinogen mRNA levels markedly lower in the fetus than in the newborn or adult (4). Whereas aspects of the regulation of angiotensinogen gene expression have been partially studied in the adult animal (5-8), the mechanisms regulating angiotensinogen gene expression in the fetal or pregnant rat have not been previously investigated.The present study was designed to investigate the response of the fetal and pregnant rat hepatic angiotensinogen gene to the pregnant state, glucocorticoid, and T3 administration. MATERIALS AND METHODSAnimal preparation. Twenty-nine time-dated pregnant WKY rats (Charles River Breeding Laboratories, Inc., Boston, MA) were housed at the University of Virginia Vivarium in opaque polypropylene cages with standard Rat Chow (Purina 5012; Ralston-Purina, St. Louis, MO) and tap water ava...