Negative regulation of angiotensinogen gene expression by glucocorticoids in fetal sheep liver.
The effect of glucocorticoids in regulating liver angiotensinogen gene expression was studied in chronically instrumented fetal sheep during the last trimester of gestation and was compared with the expression of other hepatic genes (prothrombin, factor IX, and albumin). Four sets of twins were studied at 118 d of gestation, and three sets were studied at 138 d of gestation (term, 145 d). One of each set of twins was infused intraperitoneally with cortisol (5 mumol.mL-1.h-1) for 48 h, whereas the other twin received the same volume (1 mL/h) of normal saline. Plasma cortisol concentration increased from 0.32 +/- 0.12 and 2.7 +/- 0.12 nmol/100 mL to 44.2 +/- 20.0 and 37.7 +/- 8.2 nmol/100 mL in 118- and 138-d fetuses, respectively, during the cortisol infusion; no changes were observed in fetuses infused with saline alone. At the end of the infusion period, the animals were anesthetized, the fetal liver was removed, and total cellular RNA was isolated and probed for angiotensinogen, prothrombin, factor IX, and albumin. The results demonstrated that cortisol infusion decreased angiotensinogen mRNA by 61% in 138-d fetuses and albumin mRNA expression by 2.4-fold in 118-d fetuses and by 3.4-fold in 138-d fetuses. On the other hand, cortisol had no effect on fetal factor IX gene expression but increased prothrombin mRNA levels by 65% in 118-d fetuses and 62% in 138-d fetuses. Taken together, our results suggest that, during fetal life, angiotensinogen gene expression is negatively regulated by glucocorticoids. This effect is not universal because cortisol increases fetal prothrombin gene expression.
Olson
A L
AL
Department of Pediatrics, University of Iowa, Iowa City 52242.
Robillard
J E
JE
Kisker
C T
CT
Smith
B A
BA
Perlman
S
S
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012756:Sheep
D012333:RNA, Messenger; D000808:Angiotensinogen; D006854:Hydrocortisone