Localization of the angiotensin II and its receptor subtype expression in human endometrium and identification of a novel high-affinity angiotensin II binding site.

Abstract

Angiotensin (ANG) II is not only a potent vasoconstrictor but may also be involved in the regeneration of new blood vessels. In proliferative endometrium, ANG II-like immunoreactivity was detected in glandular epithelium and stroma with negligible staining around the vascular endothelium. In contrast, in secretory endometrium intense immunostaining was seen in the perivascular stromal cells around the endometrial spiral arterioles with negligible staining of the other cell types. Quantitative receptor autoradiography using the nonselective radioligand [125I]-ANG II and subtype selective competing compounds showed that endometrium contained predominantly AT2 receptors, with relatively low expression of AT1 receptors and a novel non-AT,/non-AT2 angiotensin II recognition site that was insensitive to AT1 or AT2 selective ligands. Levels of specific ['"I]-ANG II receptor binding displayed cyclic changes during the menstrual cycle, reaching a maximum in early secretory endometrium and then decreasing in mid to late secretory endometrium to levels seen in early to mid proliferative endometrium. In situ hybridization showed AT1 receptor mRNA expression in the glands and in the endometrial blood vessels. The cyclic changes in ANG TI-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, acting as an angiogenic and mitogenic mediator. (J. Clin. Invest. 1995. 96:848-857.)

Differential expression of angiotensin II type 1 and type 2 receptors at the maternal–fetal interface: potential roles in early placental development

“…We have also described the expression of AGTR1 and AGTR2 in trophoblast subpopulations at the maternal-fetal interface, with AGTR1 primarily expressed by the differentiated trophoblasts:syncytiotrophoblast and cell column extravillous trophoblasts, and AGTR2 by proliferating villous cytotrophoblasts. AGTR2 is abundantly expressed in murine, porcine and bovine placenta (Grady et al 1991, Nielsen et al 1996, Schauser et al 1998, and it is the predominant receptor present in human cycling endometrium and myometrium (Tsuzuki et al 1994, Ahmed et al 1995. However, previous reports in the literature of its expression in human placenta are conflicting (Cooper et al 1999, Anton et al 2008, Williams et al 2010.…”

Autoantibody From Women With Preeclampsia Induces Soluble Fms-Like Tyrosine Kinase-1 Production via Angiotensin Type 1 Receptor and Calcineurin/Nuclear Factor of Activated T-Cells Signaling

“…33,34 Informed consent was obtained from the patients, and the study had the approval of the South Birmingham Ethical Committee. Five small fragments (15 to 20 mg wet weight) of placental villi were dissected from the placenta, teased apart, and placed in 24-well plates.…”

The potential role of angiotensin II in the vasculature

“…Evidence of a non-AT 1 , non-AT 2 receptor angiotensin II receptor has been obtained in human endometrial material. 51 The expression of this new subtype receptor is highest in the proliferative, angiogenic phase of the menstrual cycle. Le Noble et al 50 also proposed the existence of such a non-AT 1 , non-AT 2 receptor in the chick embryo chorio-allantois membrane.…”