Ovarian hormones modulate monocyte chemotactic protein-1 expression in endometrial cells of women with endometriosis.
Endometriosis, a frequent oestrogen-dependent disease believed to result from an aberrant proliferation of endometrial tissue outside the uterine cavity, is associated with an increased expression of monocyte chemotactic protein-1 (MCP-1) in the intrauterine endometrium. This makes it plausible that migrating endometrial cells are intrinsically able to initiate monocyte chemoattraction and activation, a phenomenon which has been consistently observed in the peritoneal cavity of patients and recently in their eutopic endometrium. To elucidate the mechanisms involved in the regulation of MCP-1 expression in eutopic endometrial cells, we studied the effects of ovarian hormones and found that oestradiol (10(-9) and 10(-8) mol/l) markedly increased MCP-1 mRNA steady-state levels and protein secretion by endometrial cells in response to interleukin-1beta (IL-1beta) (0.1 ng/ml). The IL-1beta-induced MCP-1 expression was even higher following pretreatment of cells with both oestradiol (10(-9) mol/l) and progesterone (5x10(-8) mol/l). This did not seem to be due to increased MCP-1 mRNA stability, but rather to a higher level of gene transcription. Our results provide evidence that ovarian steroids regulate, indirectly, the synthesis and the secretion of a potent chemotactic and activating factor for monocytes/macrophages by endometrial cells of women with endometriosis and reveal a new mechanism for oestradiol action.
Boucher
A
A
Department of Obstetrics and Gynecology and Department of Medicine, Faculty of Medicine, Laval University, Quebec, Canada.
Mourad
W
W
Mailloux
J
J
Lemay
A
A
Akoum
A
A
D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*
D018932:Chemokine CCL2; D007375:Interleukin-1; D011374:Progesterone; D004958:Estradiol