Dynamic regulation of estrogen receptor-alpha isoform expression in the mouse fallopian tube: mechanistic insight into estrogen-dependent production and secretion of insulin-like growth factors.
Artikel i vetenskaplig tidskrift, 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 ERbeta expression and localization in rat fallopian tubes, suggesting a potential biological function of ERbeta related to calcium-dependent ciliated beating. Here we provide for the first time insight into the less studied ERalpha isoforms, which mediate estrogen-dependent production and secretion of IGFs in vivo. First, Western blot studies revealed that three ERalpha isoforms were expressed in mouse fallopian tubes. Subsequent immunohistochemical analysis showed that ERalpha was detected in all cell types, whereas ERbeta was mainly localized in ciliated epithelial cells. Second, ERalpha isoform levels were dramatically downregulated in mouse fallopian tubes by treatment with E(2) or PPT, an ERalpha agonist, in a time-dependent manner. Third, the presence of ICI 182,780, an ER antagonist, blocked the E(2)- or PPT-induced downregulation of tubal ERalpha isoform expression in mice. However, alteration of ERalpha immunoreactivity following ICI 182,780 treatment was only detected in epithelial cells of the ampullary region. Fourth, changes in ERalpha isoform expression were found to be coupled to multiple E(2) effects on tubal growth, protein synthesis, and secretion in mouse fallopian tube tissues and fluid. In particular, E(2) 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(2) 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 ERalpha.
Insulin-Like Growth Factor I
secretion
physiology
Mice
Knockout
Animals
Mice
antagonists & inhibitors
Protein Isoforms
pharmacology
biosynthesis
metabolism
Immunohistochemistry
Vascular Endothelial Growth Factor A
Female
biosynthesis
Microscopy
pharmacology
secretion
biosynthesis
Mice
Inbred BALB C
physiology
physiology
Mice
Western
Estradiol
Inbred C57BL
Fallopian Tubes
analogs & derivatives
Estrogen Receptor alpha
Insulin-Like Growth Factor II
secretion
Fluorescence
Estrogen Antagonists
Blotting
Författare
Ruijin Shao
Göteborgs universitet
Emil Egecioglu
Göteborgs universitet
Birgitta Weijdegård
Göteborgs universitet
John J Kopchick
Julia Fernandez-Rodriguez
Göteborgs universitet
Niklas Andersson
Göteborgs universitet
Håkan Billig
Göteborgs universitet
American Journal of Physiology - Endocrinology and Metabolism
0193-1849 (ISSN) 1522-1555 (eISSN)
Vol. 293 5 E1430-42Ämneskategorier
Fysiologi
DOI
10.1152/ajpendo.00384.2007
PubMed
17848632