Fetal Expression of the Angiotensinogen Gene*

Abstract

To determine whether the angiotensinogen (Ao) gene is expressed in multiple organs of the fetal rat and the changes associated with maturation, fetal (15-20 days of gestation), newborn (1-10 days old), and adult (90 days old) rat tissues were subjected to Northern analysis and hybridization with a full length Ao complementary DNA (cDNA). Whereas Ao messenger RNA (mRNA) was undetectable in fetal livers, Ao sequences were readily detectable 1 h after birth and reached a peak at 24 h of birth. Levels remained elevated at 5 and 10 days after birth to decrease slightly at 90 days of postnatal life. Poly A+ enriched liver RNA was subjected to a similar analysis demonstrating that fetal liver Ao mRNA levels were 50-fold less than the corresponding adult levels. In contrast to the finding in the fetal liver, Ao mRNA was found in fetal brown fat, brains, and kidneys. We conclude that 1) Expression of the Ao gene is developmentally regulated in a tissue-specific manner; 2) Unlike the adult animal, the liver may not be the primary source of Ao in the fetus; 3) Alternate sources of Ao synthesis include fetal brown fat, brain, and kidneys.

Hepatic Angiotensinogen Gene Regulation in the Fetal and Pregnant Rat1

“…increase in Ao mRNA levels, as others have suggested, T3 may As we previously reported, hepatic A0 mRNA levels are lower act primarily in a permissive fashion to enhance the action of during fetal life than at any other time point during ontogeny, other hormones such as glucocorticoids (14). Further studies are increasing to adult levels dramatically within 24 h of birth (4). necessary to determine the effect of T3 on fetal A0 gene expresThe present study confirms and extends those observations, sion.…”

“…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)(6)(7)(8), the mechanisms regulating angiotensinogen gene expression in the fetal or pregnant rat have not been previously investigated.…”

Negative Regulation of Angiotensinogen Gene Expression by Glucocorticoids in Fetal Sheep Liver

“…Recently, h as previously described (16). The other twin (control) was angiotensinogen mRNA has been detected in fetal rats ( 1,4) and infused with the same volume of normal saline. The infusions in fetal sheep (5 Isolation of RNA and preparation of probes.…”

Furosemide Treatment, Angiotensin II, and Renal Growth and Development in the Rat

“…AngII is a renal growth factor, especially in the developing kidney (3)(4)(5). All of the components of the renin-angiotensin system are active in the fetus and neonate (6)(7)(8). Studies in vitro demonstrate that AngII stimulates proliferation and hypertrophy in vascular smooth muscle, mesangial, and proximal tubular cells (9)(10)(11)(12)(13)(14)(15)(16)(17).…”