Ciliated epithelial-specific and regional-specific expression and regulation of the estrogen receptor-β2 in the fallopian tubes of immature rats: a possible mechanism for estrogen-mediated transport process in vivo

Abstract

Several ERβ isoforms have been identified in human and rodent tissues, but it is unclear whether each isoform has distinctly different cellular targeting characteristics and physiological functions. We have investigated the intracellular localization and regulatory patterns for ERβ isoforms in rat fallopian tubes. Western blot analysis reveals that two ERβ isoforms corresponding to ERβ1 and ERβ2 are expressed in rat fallopian tubes. However, ERβ2 is the predominant form of ERβ in this tissue. High-resolution confocal imaging and immunohistochemical analysis provide ample evidence that ERβ expression is limited almost exclusively to the ciliated epithelial cells, in contrast to ERα, which is widely distributed. Furthermore, within the ciliated epithelial cells, ERβ is colocalized with β-tubulin IV at stem portion of the cilia. We show that ERβ2 protein expression is tightly regulated by E2 or DPN in a time-dependent manner without changes in ERβ1 expression. These estrogenic effects are inhibited by an ER antagonist, ICI 182,780. In addition, significant alteration of ERβ immunoreactivity is detected only histologically in the ampullary region. Since the cilia are considered an essential determinant of tubal transport, we further demonstrate that E2- or DPN-induced ERβ2 activation is associated with alterations in tubal protein expression crucial for the regulation of calcium-dependent ciliary beating. Given the coordinated regulation and interaction of ER and progesterone receptor in the cilia, we hypothesize that tubal ERβ2 may facilitate the estrogen-mediated transport process by processing protein-protein interaction under physiological and/or pathological conditions. We show for the first time that a previously unrecognized localization of ERβ isoform in rat fallopian tubes can combine with estrogen to individually control the expression of ER β-isoforms in normal target tissues.