LOCALIZATION OF THE ANGIOTENSIN-II AND ITS RECEPTOR SUBTYPE EXPRESSION IN HUMAN ENDOMETRIUM AND IDENTIFICATION OF A NOVEL HIGH-AFFINITY ANGIOTENSIN-II BINDING-SITE

Angiotensin (ANG) II is not only a potent vasoconstrictor but may also be involved in the regeneration of new blood vessels: In proliferativ e endometrium, ANG II-like immunoreactivity was detected in glandular epithelium and stroma with negligible staining around the vascular end othelium, In contrast, in secretory endometrium intense immunostaining was seen in the perivascular stromal cells around the endometrial spi ral arterioles with negligible staining of the other cell types. Quant itative receptor autoradiography using the nonselective radioligand [I -125]-ANG II and subtype selective competing compounds showed that end ometrium contained predominantly AT(2) receptors, with relatively low expression of AT(1) receptors and a novel non-AT(1)/non-AT(2) angioten sin II recognition site that was insensitive to AT(1) or AT(2) selecti ve ligands, Levels of specific [I-125]-ANG II receptor binding display ed cyclic changes during the menstrual cycle, reaching a maximum in ea rly secretory endometrium and then decreasing in mid to late secretory endometrium to levels seen in early to mid proliferative endometrium. In situ hybridization showed AT(1) receptor mRNA expression in the gl ands and in the endometrial blood vessels, The cyclic changes in ANG I I-like immunoreactivity together with expression of both the known and the novel AT receptor subtypes imply that this octopeptide may play a dual role both in the control of the uterine vascular bed and also in the regeneration of the endometrium after endometrial shedding, actin g as an angiogenic and mitogenic mediator.