Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis. (September 2016)

• Record Type: Journal Article
• Authors: Grandi, Giovanni; Mueller, Michael D.; Papadia, Andrea; Kocbek, Vida; Bersinger, Nick A.; Petraglia, Felice; Cagnacci, Angelo; McKinnon, Brett
• Is Part Of: Journal of reproductive immunology. Volume 117(2016)
• Page Start: 30
• Page End: 38
• Publication Date: 2016-09
• Subjects: Endometriosis -- Progestin -- Inflammation -- Progesterone receptor -- Glucocorticoid receptor -- Mineralocorticoid receptor -- Membrane progesterone receptor -- Androgen receptor; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2016.06.004
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: Inflammation influences progestins targets of endometrial cells refluxed in ectopic sites. Inflammatory cytokines, like TNFα and IL-1β, can reduce the expression of progesterone receptors. The same cytokines can increase the expression of glucocorticoid receptors. These findings could contribute to the progesterone resistance observed in endometriosis. This findings may suggest the design of more targeted therapies with an effective local activity. 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.