{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:04:18Z","timestamp":1762160658677},"reference-count":68,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p>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\u03b2 expression and localization in rat fallopian tubes, suggesting a potential biological function of ER\u03b2 related to calcium-dependent ciliated beating. Here we provide for the first time insight into the less studied ER\u03b1 isoforms, which mediate estrogen-dependent production and secretion of IGFs in vivo. First, Western blot studies revealed that three ER\u03b1 isoforms were expressed in mouse fallopian tubes. Subsequent immunohistochemical analysis showed that ER\u03b1 was detected in all cell types, whereas ER\u03b2 was mainly localized in ciliated epithelial cells. Second, ER\u03b1 isoform levels were dramatically downregulated in mouse fallopian tubes by treatment with E<jats:sub>2<\/jats:sub>or PPT, an ER\u03b1 agonist, in a time-dependent manner. Third, the presence of ICI 182,780, an ER antagonist, blocked the E<jats:sub>2<\/jats:sub>- or PPT-induced downregulation of tubal ER\u03b1 isoform expression in mice. However, alteration of ER\u03b1 immunoreactivity following ICI 182,780 treatment was only detected in epithelial cells of the ampullary region. Fourth, changes in ER\u03b1 isoform expression were found to be coupled to multiple E<jats:sub>2<\/jats:sub>effects on tubal growth, protein synthesis, and secretion in mouse fallopian tube tissues and fluid. In particular, E<jats:sub>2<\/jats:sub>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 E<jats:sub>2<\/jats:sub>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\u03b1.<\/jats:p>","DOI":"10.1152\/ajpendo.00384.2007","type":"journal-article","created":{"date-parts":[[2007,9,12]],"date-time":"2007-09-12T03:48:40Z","timestamp":1189568920000},"page":"E1430-E1442","source":"Crossref","is-referenced-by-count":51,"title":["Dynamic regulation of estrogen receptor-\u03b1 isoform expression in the mouse fallopian tube: mechanistic insight into estrogen-dependent production and secretion of insulin-like growth 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