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Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis.
Am J Pathol 2012; 181(3):917-27AJ

Abstract

Immune-endocrine interplay may play a major role in the pathogenesis of endometriosis. In the present study, we have investigated the interaction between macrophage migration inhibitory factor (MIF), a major pro-inflammatory and growth-promoting factor markedly expressed in active endometriotic lesions, and estradiol (E(2)) in ectopic endometrial cells. Our data showed a significant increase of MIF protein secretion and mRNA expression in endometriotic cells in response to E(2). MIF production was blocked by Fulvestrant, an estrogen receptor (ER) antagonist, and induced by ERα and ERβ selective agonists propyl-pyrazole-triol (PPT) and diarylpropionrile (DPN), respectively, thus demonstrating a specific receptor-mediated effect. Cell transfection with MIF promoter construct showed that E(2) significantly stimulates MIF promoter activity. Interestingly, our data further revealed that MIF reciprocally stimulates aromatase protein and mRNA expression via a posttranscriptional mRNA stabilization mechanism, that E(2) itself can upregulate aromatase expression, and that inhibition of endogenous MIF, using MIF specific siRNA, significantly inhibits E(2)-induced aromatase. Thus, the present study revealed the existence of a local positive feedback loop by which estrogen acts directly on ectopic endometrial cells to upregulate the expression of MIF, which, in turn, displays the capability of inducing the expression of aromatase, the key and rate-limiting enzyme for estrogen synthesis. Such interplay may have a considerable impact on the development of endometriosis.

Authors+Show Affiliations

Laboratory of Reproductive Endocrinology, Research Center, Hospital of Saint-François of Assisi CHUQ, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22759564

Citation

Veillat, Véronique, et al. "Macrophage Migration Inhibitory Factor Is Involved in a Positive Feedback Loop Increasing Aromatase Expression in Endometriosis." The American Journal of Pathology, vol. 181, no. 3, 2012, pp. 917-27.
Veillat V, Sengers V, Metz CN, et al. Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis. Am J Pathol. 2012;181(3):917-27.
Veillat, V., Sengers, V., Metz, C. N., Roger, T., Leboeuf, M., Mailloux, J., & Akoum, A. (2012). Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis. The American Journal of Pathology, 181(3), pp. 917-27. doi:10.1016/j.ajpath.2012.05.018.
Veillat V, et al. Macrophage Migration Inhibitory Factor Is Involved in a Positive Feedback Loop Increasing Aromatase Expression in Endometriosis. Am J Pathol. 2012;181(3):917-27. PubMed PMID: 22759564.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis. AU - Veillat,Véronique, AU - Sengers,Valérie, AU - Metz,Christine N, AU - Roger,Thierry, AU - Leboeuf,Mathieu, AU - Mailloux,Jacques, AU - Akoum,Ali, Y1 - 2012/06/30/ PY - 2011/08/24/received PY - 2012/04/20/revised PY - 2012/05/14/accepted PY - 2012/7/5/entrez PY - 2012/7/5/pubmed PY - 2012/11/9/medline SP - 917 EP - 27 JF - The American journal of pathology JO - Am. J. Pathol. VL - 181 IS - 3 N2 - Immune-endocrine interplay may play a major role in the pathogenesis of endometriosis. In the present study, we have investigated the interaction between macrophage migration inhibitory factor (MIF), a major pro-inflammatory and growth-promoting factor markedly expressed in active endometriotic lesions, and estradiol (E(2)) in ectopic endometrial cells. Our data showed a significant increase of MIF protein secretion and mRNA expression in endometriotic cells in response to E(2). MIF production was blocked by Fulvestrant, an estrogen receptor (ER) antagonist, and induced by ERα and ERβ selective agonists propyl-pyrazole-triol (PPT) and diarylpropionrile (DPN), respectively, thus demonstrating a specific receptor-mediated effect. Cell transfection with MIF promoter construct showed that E(2) significantly stimulates MIF promoter activity. Interestingly, our data further revealed that MIF reciprocally stimulates aromatase protein and mRNA expression via a posttranscriptional mRNA stabilization mechanism, that E(2) itself can upregulate aromatase expression, and that inhibition of endogenous MIF, using MIF specific siRNA, significantly inhibits E(2)-induced aromatase. Thus, the present study revealed the existence of a local positive feedback loop by which estrogen acts directly on ectopic endometrial cells to upregulate the expression of MIF, which, in turn, displays the capability of inducing the expression of aromatase, the key and rate-limiting enzyme for estrogen synthesis. Such interplay may have a considerable impact on the development of endometriosis. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/22759564/Macrophage_migration_inhibitory_factor_is_involved_in_a_positive_feedback_loop_increasing_aromatase_expression_in_endometriosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(12)00422-1 DB - PRIME DP - Unbound Medicine ER -