Production of interleukin-1{alpha} by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1{alpha} released upon ovarian steroids withdrawal

Pretto, Chrystel;Gaide Chevronnay, Héloïse P.;Cornet, Patricia B;Galant, Christine;Henriet, Patrick;et.al.
(2008) Journal of Clinical Endocrinology and Metabolism — Vol. 93, n° 10, p. 4126-4134 (2008)

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Authors
  • Pretto, ChrystelUCLouvain
    Author
  • Gaide Chevronnay, Héloïse P.UCLouvain
    Author
  • Cornet, Patricia BUCLouvain
    Author
  • Galant, Christineorcid-logoUCLouvain
    Author
  • Delvaux, DenisUCLouvain
    Author
  • Courtoy, PierreUCLouvain
    Author
  • Marbaix, EtienneUCLouvain
    Author
  • Henriet, PatrickUCLouvain
    Author
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Abstract
Context: Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived interleukin-1alpha (IL-1alpha) is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown. Objective and design: Variations of endometrial IL-1alpha mRNA and protein along the menstrual cycle and during dysfunctional bleeding were determined using RT-PCR, in situ hybridization and immunolabeling. The mechanism of EP control was analyzed using culture of explants, laser capture microdissection and purified cells. Data were compared with expression changes of IL-1beta and IL-1 receptor antagonist. Results: IL-1alpha is synthesized by epithelial cells throughout the cycle but E and/or P prevent(s) its release. In contrast, endometrial stromal cells produce IL-1alpha only at menses and during irregular bleeding in areas of tissue breakdown. Stromal expression of IL-1alpha, like that of MMP-1, is repressed by P (alone or with E) but triggered by epithelium-derived IL-1alpha released upon EP withdrawal. Conclusions: Our experiments in cultured endometrium suggest that IL-1alpha released by epithelial cells triggers the production of IL-1alpha by stromal cells in a paracrine amplification loop to induce MMP-1 expression during menstruation and dysfunctional bleeding. All three steps of this amplification cascade are repressed by EP. Keywords. Interleukin-1; menstrual cycle; progesterone; estradiol; gene regulation; dysfunctional bleeding.
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Pretto, C., Gaide Chevronnay, H. P., Cornet, P. B., Galant, C., Delvaux, D., Courtoy, P., Marbaix, E., & Henriet, P. (2008). Production of interleukin-1{alpha} by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1{alpha} released upon ovarian steroids withdrawal. Journal of Clinical Endocrinology and Metabolism, 93(10), 4126-4134. https://doi.org/10.1210/jc.2007-2636 (Original work published 2008)