Colocalization of progesterone receptors A and B by dual immunofluorescent histochemistry in human endometrium during the menstrual cycle

The human progesterone receptor (PR) is expressed as two isoforms, PRA and PRE, that function as ligand-activated transcription factors. In vitro studies suggest that the isoforms differ functionally and that the relative levels in a target cell may determine the nature and magnitude of response to progesterone. However, it is not known whether the two isoforms are normally coexpressed in vivo. To understand the functional significance of relative PR isoform expression in normal physiology, it is essential to determine whether PRA and PRE are coexpressed in the same cell. This study reports the development of a dual immunofluorescent staining technique to demonstrate PRA and PRE proteins by single cell analysis in the same tissue section of human endometrium during the menstrual cycle. PRA and PRE are coexpressed in target cells of the human uterus. In the glands, PRA and PRE were expressed before subnuclear vacuole formation and glycogenolysis, implicating both isoforms in this process, whereas persistence of PRE during the midsecretory phase suggested its significance in glandular secretion. In the stroma, the predominance of PRA throughout the cycle implicates this isoform in postovulatory progesterone-mediated events. These results support the view that PRA. and PRE mediate distinct pathways of progesterone action in the glandular epithelium and stroma of the human uterus throughout the menstrual cycle.