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This version published online on May 18, 2006
Endocrinology, doi:10.1210/en.2006-0264
A more recent version of this article appeared on August 1, 2006
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Submitted on February 28, 2006
Accepted on May 3, 2006

IL-11 signalling components STAT3 and SOCS3 regulate human endometrial stromal cell differentiation

Evdokia Dimitriadis*, Chelsea Stoikos, Yee-Lee Tan, and Lois A. Salamonsen

Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, VIC 3168, Australia

* To whom correspondence should be addressed. E-mail: evdokia.dimitriadis{at}princehenrys.org.

The differentiation of endometrial stromal cells into decidual cells (decidualization) is critical for embryo implantation but the mechanisms remain poorly defined. Numerous paracrine agents including interleukin (IL)-11 promote human endometrial stromal cell (HESC) decidualization. IL-11 signaling is transduced by the signal transducers and activators of transcription (STAT) proteins. Suppressors of cytokine signaling (SOCS) proteins are stimulated in response to cytokine-inducible STAT phosphorylation, acting in a negative-feedback mechanism to hinder cytokine receptor activity. This study examined the role of IL-11 signal transduction components in HESC decidualization in an ex vivo model. Cells were induced to differentiate with estrogen (E)+medroxy-progesterone-acetate (P) or cAMP (assessed by prolactin secretion) and resulted in increased STAT3 and SOCS3. E+P maximally stimulated STAT3 while cAMP maximally stimulated SOCS3 during decidualization suggesting E+P and cAMP differentially regulated the signaling components. IL-11 stimulated the phosphorylation (p) of STAT3 and SOCS3 mRNA and protein. Antiprogestin (onapristone) added to decidualizing cells attenuated STAT3 protein but increased SOCS3 mRNA and protein suggesting regulation via both ligand dependent and independent progesterone-receptor pathways. SOCS3 overexpression in HESC reduced IL-11 induced pSTAT3 and retarded decidualization, indicating that SOCS3 is a critical regulator of differentiation. Immunoreactive pSTAT3 and SOCS3 were all present in decidualized stromal cells, epithelial cells and leukocytes in human endometrium. These data support a role for IL-11 via pSTAT3 and SOCS3 in initiating and progressing decidualization.


Key words: progesterone • cAMP • differentiation • interleukin 11 • STAT3 • SOCS3 • endometrial stromal cells




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