Expression of calcitonin gene-related peptide receptor components, calcitonin receptor-like receptor and receptor activity modifying protein 1, in the rat placenta during pregnancy and their cellular localization

Abstract

Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental function during pregnancy. The present study was aimed to investigate mRNA expression of CGRP-A receptor components, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) in the rat placenta. Immunohistochemical staining of rat placentas obtained on day 18 of pregnancy using polyclonal anti-CRLR and RAMP, antibodies revealed that labelling was specifically concentrated in the cytotrophoblast and syncytium in labyrinth, trophoblastic giant cells and basophilic cells in trophospongial cell layer, and endothelium and smooth muscle cells in fetal vessels. The intensity of staining was reduced in all these cells except in the syncytium in placentas obtained during labour. RT-PCR analysis showed that mRNA expression of CRLR and RAMP1 was significantly higher in the rat placenta from gestation day 17 to day 22, than during labour. During pregnancy, 17β-estradiol inhibits, while progesterone stimulates, placental mRNA and proteins for CRLR and RAMP1. Antiestrogen, ICI 182780, increased, whereas antiprogesterone, RU 486, inhibited the expression of both CRLR and RAMP1. In summary, we demonstrate the presence and cellular localization of CRLR and RAMP1 in the rat placenta. Elevated placental CRLR and RAMP, may be involved in CGRP-related increases in blood flow and therefore fetal growth and decreases at term labour may help minimize the blood loss.