Involvement of the angiotensin II type 2 receptor in apoptosis during human fetal adrenal gland development

The aim of this study was to establish a link between the highly expressed angiotensin II (Ang II) type 2 receptor (AT(2)) in human fetal adrenal cell s and the proposed apoptotic activity in the center of the gland. There was an important increase in apoptotic DNA fragmentation with age in adrenal g lands of fetuses from 15-20 weeks gestation. Adrenal cells showing the char acteristic apoptotic internucleosomal DNA fragmentation were localized in t he central portion of the fetal zone. In cells cultured for 24 h, Ang II, v ia the AT(2) receptor, induced DNA fragmentation and cleavage of the DNA re pair enzyme, poly-(ADP-ribose) polymerase. Furthermore, characteristic memb rane blebbing was observed specifically on cells of the fetal zone. Immunof luorescence studies demonstrated that stimulation with Ang II or CGP 42112 (an agonist of the AT(2) receptor) strongly modified the actin network, now localized exclusively along the plasma membrane, with a predominance of la beling at the base of the bleb formation. This rearrangement of actin distr ibution was different in cells from the definitive zone, corroborating the observation that these cells express many more Ang II type 1 receptors (AT( 1)) than AT(2) receptors. Taken together, our data indicate that the AT(2) receptor is involved in the apoptotic process observed in the human fetal a drenal gland and could participate in the morphological changes occurring a fter birth, leading to involution of the fetal zone.