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 plas ma. To understand why plasma ACE levels are elevated in children compa red 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 o f endothelial ACE, the abundance of ACE mRNA and the microsomal ACE co ncentration increased progressively and tripled during the first 3 mo. This large increase reflects, at least in part, development of the ca pillary network. In plasma, ACE levels rose dramatically a few days af ter birth and decreased toward adult values after the 14th day of life . Because the elevation of ACE in plasma was contemporary to thyroid m aturation, the effect of perinatal suppression of thyroid function by propylthiouracil was studied. Hypothyroidism slightly delayed the evol ution of ACE in lung but blunted the postnatal rise in plasma ACE leve l. 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 mal e germinal cells. In the intestine, ACE mRNA levels and ACE activity w ere very high at birth and then decreased dramatically during the next 2 wk. In the kidney, they were low and decreased further during growt h. In the testis, ACE mRNA level and ACE activity increased dramatical ly at puberty, with activation of the intragenic germinal ACE promoter and transcription of a shorter form of mRNA. Thus the regulation of A CE gene expression during postnatal development is organ specific.