THE ANGIOTENSIN AT(2) RECEPTOR IS PRESENT IN THE HUMAN FETAL ADRENAL-GLAND THROUGHOUT THE 2ND TRIMESTER OF GESTATION

The aim of the present study was to characterize distribution and phar macological properties of angiotensin II (Ang II) receptors in human f etal adrenals frozen immediately after removal. Autoradiographic studi es indicate that Ang II receptors are present throughout the gland. Co incubations with DUP 753, a specific antagonist of the AT(1) receptor, and with PD 123319, a specific antagonist of the AT(2) receptor, reve al that Ang II receptors are mainly of the type 2. The AT(1) receptors are detected after 16 weeks of gestation at the periphery of the glan d. Binding of I-125-Ang II to membrane preparations is dose-dependent and saturable. Competition studies and Scatchard analysis reveal a hom ogenous population of high-affinity AT(2) binding sites (K-d = 0.68 +/ - 0.1 nmol/L). Binding capacities decrease from 1080 +/- 304 fmol/mg p rotein at 14 weeks to 275 +/- 55 fmol/mg protein at 21 weeks. However, when fetal adrenal cells are prepared and cultured for 6 days, the pr oportion of AT(1) receptors increases, indicating that culture conditi ons induce expression of the AT(1) receptor. These results differ from those obtained in adult glands, where autoradiographic studies reveal that the AT(1) receptors are found mainly in zona glomerulosa and AT( 2) receptors mainly in the medulla. These data suggest that the AT(2) receptors could be involved in the morphological or functional differe ntiation of the human fetal adrenal gland.