Regulation of ACE gene expression and plasma levels during rat postnatal development.
Angiotensin I-converting enzyme (kininase II, ACE) is a transmembrane ectoenzyme of vascular endothelial cells that is also secreted in plasma. To understand why plasma ACE levels are elevated in children compared with adults, the age-related changes in ACE mRNA and enzyme levels were studied in 1-day- to 3-mo-old rats. In the lung, a rich source of endothelial ACE, the abundance of ACE mRNA and the microsomal ACE concentration increased progressively and tripled during the first 3 mo. This large increase reflects, at least in part, development of the capillary network. In plasma, ACE levels rose dramatically a few days after birth and decreased toward adult values after the 14th day of life. Because the elevation of ACE in plasma was contemporary to thyroid maturation, the effect of perinatal suppression of thyroid function by propylthiouracil was studied. Hypothyroidism slightly delayed the evolution of ACE in lung but blunted the postnatal rise in plasma ACE levels. A 3,5,3'-triiodothyronine injection to 14-day-old hypothyroid rats failed to alter ACE mRNA levels in the lung. Thus thyroid hormones are involved in the postnatal rise in plasma ACE levels but act probably on the posttranslational proteolytic pathway involved in ACE secretion by endothelial cells or on an unknown extrapulmonary ACE source. ACE gene expression is also developmentally regulated in epithelia and male germinal cells. In the intestine, ACE mRNA levels and ACE activity were very high at birth and then decreased dramatically during the next 2 wk. In the kidney, they were low and decreased further during growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Costerousse
O
O
Institut National de la Santé et de la Recherche Médicale Unité 367, Paris, France.
Allegrini
J
J
Huang
H
H
Bounhik
J
J
Alhenc-Gelas
F
F
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006728:Hormones / Q000097:blood; D007037:Hypothyroidism / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology
D006728:Hormones; D012333:RNA, Messenger; D014284:Triiodothyronine; D007703:Peptidyl-Dipeptidase A