The angiotensin AT(2) receptor is present in the human fetal adrenal gland throughout the second trimester of gestation

The aim of the present study was to characterize distribution and pharmacological properties of angiotensin II (Ang II) receptors in human fetal adrenals frozen immediately after removal. Autoradiographic studies indicate that Ang II receptors are present throughout the gland. Coincubations with DUP 753, a specific antagonist of the AT(1) receptor, and with PD 123319, a specific antagonist of the AT(2) receptor, reveal 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 gland. Binding of I-125-Ang II to membrane preparations is dose-dependent and saturable. Competition studies and Scatchard analysis reveal a homogenous population of high-affinity AT(2) binding sites (K-d = 0.68 +/- 0.1 nmol/L). Binding capacities decrease from 1080 +/- 304 fmol/mg protein 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 proportion of AT(1) receptors increases, indicating that culture conditions 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 differentiation of the human fetal adrenal gland.