Hepatic angiotensinogen gene regulation in the fetal and pregnant rat.
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.
Everett
A D
AD
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908.
Chevalier
R L
RL
Gomez
R A
RA
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D014284:Triiodothyronine / Q000494:pharmacology
D012333:RNA, Messenger; D014284:Triiodothyronine; D000808:Angiotensinogen; D003907:Dexamethasone