Estrogen action is mediated via two subtypes of the estrogen receptor (ER), usually referred to as ERα and ERβ. We have previously compared the spatial and temporal expressions of ERα and ERβ proteins in human endometrium and reported that endothelial cells exclusively express ERβ. In the present study we have extended our investigations to compare the pattern of expression of wild-type (ERβ1) and a newly identified ERβ variant isoform (ERβcx/β2) that lacks the ability to bind steroids.

mRNAs encoding both ERβ1 and ERβcx/β2 receptors were identified in human endometrial extracts by RT-PCR. Quantitative TaqMan R-TPCR demonstrated that levels of total mRNAs were increased significantly premenstrually as circulating progesterone levels declined. ERβ1 and ERβcx/β2 proteins were identified within multiple cell types within the endometrium using isotype-specific monoclonal antibodies; immunoexpression of ERβcx/β2 appeared less intense than that of ERβ1 in endometrial glandular epithelium and endothelial cells. Immunoexpression of ERβ1 appeared unchanged throughout the menstrual cycle. In contrast, levels of ERβcx/β2-specific immunoreactivity were specifically reduced in gland cells within the functional layer, but not in those of the basal layer, in the midsecretory phase. It is possible that coexpression of ERβcx/β2 in cells containing ERβ1 and/or ERα may modulate the effects of estrogens on the endometrium.