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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/E1430    most recent 00384.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shao, R. Articles by Billig, H. Search for Related Content PubMed PubMed Citation Articles by Shao, R. Articles by Billig, H.

Dynamic regulation of estrogen receptor- isoform expression in the mouse fallopian tube: mechanistic insight into estrogen-dependent production and secretion of insulin-like growth factors

¹Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; ²Edison Biotechnology Institute, Konneker Research Laboratories, Ohio University, Athens, Ohio; and ³Centre for Cellular Imaging, Core facilities, and ⁴Division of Endocrinology, Department of Internal Medicine, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden

Submitted 19 June 2007 ; accepted in final form 3 September 2007

Estrogen receptors (ERs) are members of the nuclear receptor superfamily and are involved in regulation of fallopian tube functions (i.e., enhancement of protein secretion, formation of tubal fluid, and regulation of gamete transport). However, the ER subtype-mediated mechanisms underlying these processes have not been completely clarified. Recently, we identified ER expression and localization in rat fallopian tubes, suggesting a potential biological function of ER related to calcium-dependent ciliated beating. Here we provide for the first time insight into the less studied ER isoforms, which mediate estrogen-dependent production and secretion of IGFs in vivo. First, Western blot studies revealed that three ER isoforms were expressed in mouse fallopian tubes. Subsequent immunohistochemical analysis showed that ER was detected in all cell types, whereas ER was mainly localized in ciliated epithelial cells. Second, ER isoform levels were dramatically downregulated in mouse fallopian tubes by treatment with E₂ or PPT, an ER agonist, in a time-dependent manner. Third, the presence of ICI 182,780, an ER antagonist, blocked the E₂- or PPT-induced downregulation of tubal ER isoform expression in mice. However, alteration of ER immunoreactivity following ICI 182,780 treatment was only detected in epithelial cells of the ampullary region. Fourth, changes in ER isoform expression were found to be coupled to multiple E₂ effects on tubal growth, protein synthesis, and secretion in mouse fallopian tube tissues and fluid. In particular, E₂ exhibited positive regulation of IGF-I and IGF-II protein levels. Finally, using growth hormone receptor (GHR) gene-disrupted mice, we showed that regulation by E₂ of IGF production was independent of GH-induced GHR signaling in mouse fallopian tubes in vivo. These data, together with previous studies from our laboratory, suggest that the long-term effects of estrogen agonist promote IGF synthesis and secretion in mouse tubal epithelial cells and fallopian tube fluid via stimulation of ER.

estrogen receptor- isoforms; tubal epithelial cells