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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/C140    most recent 00047.2009v1 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 PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Shao, R. Articles by Billig, H. PubMed PubMed Citation Articles by Shao, R. Articles by Billig, H.

RECEPTORS AND SIGNAL TRANSDUCTION

Downregulation of cilia-localized Il-6R by 17β-estradiol in mouse and human fallopian tubes

¹Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, and ²Centre for Cellular Imaging, Core Facilities, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; ³Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; and ⁴Center for Bone Research at the Sahlgrenska Academy, Sahlgrenska University Hospital and Sahlgrenska Academy, Gothenberg, Sweden

Submitted 23 January 2009 ; accepted in final form 30 April 2009

The action of interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6R and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6R is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17β-estradiol (E₂), but not progesterone (P₄), causes a time-dependent decrease in IL-6R expression, which is blocked by the estrogen receptor (ER) antagonist ICI-182,780. Exposure of different ER-selective agonists propyl-(1H)-pyrazole-1,3,5-triyl-trisphenol or 2,3-bis-(4-hydroxyphenyl)-propionitrile demonstrated an ER subtype-specific regulation of IL-6R in mouse fallopian tubes. In contrast to IL-6R, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6R and gp130 in IL-6 knockout mice was found to be normal; however, E₂ treatment increased IL-6R, but not gp130, in IL-6 knockout mice when compared with wild-type mice. Furthermore, expression levels of IL-6R, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings open the posibility that cilia-specific IL-6R may play a role in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6R in the fallopian tube.

estrogen; oocyte-cumulus complex transport