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 E1430-42

Ämneskategorier

Fysiologi

DOI

10.1152/ajpendo.00384.2007

PubMed

17848632