Giovanni Grandi1,2, Michael Mueller2,3, Nick Bersinger2,3, Andrea Papadia3, Konstatinos Nirgianakis2,3, Angelo Cagnacci1, Brett McKinnon4,5. 1. Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy. 2. Department of Clinical Research, University of Berne, Berne, Switzerland. 3. Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Berne, Switzerland. 4. Department of Clinical Research, University of Berne, Berne, Switzerland. brett.mckinnon@dkf.unibe.ch. 5. Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, Berne, Switzerland. brett.mckinnon@dkf.unibe.ch.
Abstract
PROBLEM: Endometriosis is an estrogen-dependent inflammatory disease. Progestins are a first-line treatment for endometriosis via activation of pituitary progesterone receptors and suppression of systemic estrogen: a less than optimal treatment. Increasing evidence is beginning to show that progestins may also influence local endometriotic cells, which may contribute to their clinical efficacy. METHOD OF STUDY: Endometrial stromal cells (ESC) isolated from women with endometriosis were cultured with TNF-α to simulate an inflammatory environment. ESC were treated with the progestins, medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), or dienogest (DNG) and cytokine mRNA production, protein secretion, and cell viability measured. RESULTS: DNG, NETA, and MPA suppressed the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1 from ESC. DNG and NETA only reduced the TNF-α-stimulated mRNA production. All three progestins suppressed TNF-α-stimulated ESC proliferation. CONCLUSION: Progestins may influence endometriotic stromal cells altering the inflammatory microenvironment and their clinical efficacy.
PROBLEM: Endometriosis is an estrogen-dependent inflammatory disease. Progestins are a first-line treatment for endometriosis via activation of pituitary progesterone receptors and suppression of systemic estrogen: a less than optimal treatment. Increasing evidence is beginning to show that progestins may also influence local endometriotic cells, which may contribute to their clinical efficacy. METHOD OF STUDY: Endometrial stromal cells (ESC) isolated from women with endometriosis were cultured with TNF-α to simulate an inflammatory environment. ESC were treated with the progestins, medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), or dienogest (DNG) and cytokine mRNA production, protein secretion, and cell viability measured. RESULTS:DNG, NETA, and MPA suppressed the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1 from ESC. DNG and NETA only reduced the TNF-α-stimulated mRNA production. All three progestins suppressed TNF-α-stimulated ESC proliferation. CONCLUSION: Progestins may influence endometriotic stromal cells altering the inflammatory microenvironment and their clinical efficacy.
Authors: Rebecca S Hornung; William L Benton; Sirima Tongkhuya; Lynda Uphouse; Phillip R Kramer; Dayna Loyd Averitt Journal: Front Integr Neurosci Date: 2020-05-08