title: Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis.
abstract: Endometriosis is an estrogen-dependent disease characterised by the growth of endometrial epithelial and stromal cells outside the uterus creating a chronic inflammatory environment that further contributes to disease progression. The first choice treatment for endometriosis is currently progestin mediated hormone modulation. In addition to their progestogenic activity however, progestins also have the potential to bind to other nuclear receptors influencing their local activity on endometriotic cells. This local activity will be dependent on the steroid hormone receptor expression that occurs in endometrial cells in a chronic inflammatory environment. We therefore aimed to quantify receptors targeted by progestins in endometrial stromal cells after exposure to inflammation. Using primary endometrial stromal cells isolated from women with endometriosis we examined the mRNA and protein expression of the progesterone receptors A and B, membrane progesterone receptors 1 and 2, androgen receptors, mineralocorticoid receptors and glucocorticoid receptors after exposure to the inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). The results indicate that both cytokines reduced the expression of progesterone receptors and increased the expression of the glucocorticoid receptors in the endometrial stromal cells. The change in expression of progestin targets in endometrial stromal cells in an inflammatory environment could contribute to the progesterone resistance observed in endometriotic cells and ultimately influence the design of hormonal therapies aimed at treating this disease.
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grandi
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Effingerstrasse 102, Berne CH-3010, Switzerland; Department of Clinical Research, University of Berne, Murtenstrasse 35, Berne CH-3010, Switzerland.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mueller
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Effingerstrasse 102, Berne CH-3010, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Papadia
authors.affiliation: Department of Clinical Research, University of Berne, Murtenstrasse 35, Berne CH-3010, Switzerland.
authors.forename: Vida
authors.initials: V
authors.lastname: Kocbek
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Effingerstrasse 102, Berne CH-3010, Switzerland; Department of Clinical Research, University of Berne, Murtenstrasse 35, Berne CH-3010, Switzerland.
authors.forename: Nick A
authors.initials: NA
authors.lastname: Bersinger
authors.affiliation: Policlinico "Santa Maria delle Scotte", Department of Molecular and Development Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Cagnacci
authors.affiliation: Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Effingerstrasse 102, Berne CH-3010, Switzerland; Department of Clinical Research, University of Berne, Murtenstrasse 35, Berne CH-3010, Switzerland. Electronic address: brett.mckinnon@dkf.unibe.ch.
authors.forename: Brett
authors.initials: B
authors.lastname: McKinnon
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D004715:Endometriosis / Q000188:drug therapy / Q000276:immunology*; D004717:Endometrium / Q000473:pathology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D011247:Pregnancy; D011372:Progestins / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D053583:Interleukin-1beta; D011372:Progestins; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha
keywords: Androgen receptor; Endometriosis; Glucocorticoid receptor; Inflammation; Membrane progesterone receptor; Mineralocorticoid receptor; Progesterone receptor; Progestin