The angiotensin AT2 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 AT1 receptor, and with PD 123319, a specific antagonist of the AT2 receptor, reveal that Ang II receptors are mainly of the type 2. The AT1 receptors are detected after 16 weeks of gestation at the periphery of the gland. Binding of 125I-Ang II to membrane preparations is dose-dependent and saturable. Competition studies and Scatchard analysis reveal a homogenous population of high-affinity AT2 binding sites (Kd = 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 AT1 receptors increases, indicating that culture conditions induce expression of the AT1 receptor. These results differ from those obtained in adult glands, where autoradiographic studies reveal that the AT1 receptors are found mainly in zona glomerulosa and AT2 receptors mainly in the medulla. These data suggest that the AT2 receptors could be involved in the morphological or functional differentiation of the human fetal adrenal gland.
Breault
L
L
Service of Endocrinology, University of Sherbrooke, Quebec, Canada.
Lehoux
J G
JG
Gallo-Payet
N
N
D000311:Adrenal Glands / Q000196:embryology / Q000378:metabolism*; D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D001345:Autoradiography; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D019808:Losartan; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D014018:Tissue Distribution
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan