The role of SRC1 and SRC2 in steroid-induced SDF1 expression in normal and ectopic endometrium

Abstract

To compare the expression patterns of steroid receptor coactivators (SRCs) and steroid-induced stromal cell-derived factor 1 (CXCL12 (SDF1)) in normal and ectopic endometrium and to explore the roles of NCOA1 (SRC1) and NCOA2 (SRC2) in the steroid-induced CXCL12 expression in normal and ectopic endometrial stromal cells (ESCs). The NCOA1, NCOA2, NCOA3 (SRC3), and CXCL12 (SDF1)a mRNA levels in normal and ectopic endometrium were analyzed by quantitative real-time PCR. Steroid-induced CXCL12 expression was detected by the ELISA method and the chemotactic activity of conditioned supernatant to monocyte was assessed by the Boyden chamber method before and after the silencing of NCOA1 or NCOA2 with siRNA in normal and ectopic ESCs. The expression of NCOA1 and CXCL12 in ectopic endometrium was significantly greater than that in normal endometrium in the secretory phase. Progesterone (P 4 ) was able to significantly inhibit estradiol (E 2 )-stimulated CXCL12 expression in normal and ectopic ESCs. The inhibitory rate of P 4 in ectopic ESCs at 72 and 96 h was significantly lower than that in normal ESCs. Silencing of NCOA1 but not NCOA2 significantly reduced the E 2 -induced CXCL12 expression in normal and ectopic ESCs. The ability of P 4 to inhibit E 2 -induced CXCL12 expression and monocyte chemotaxis in normal and ectopic ESCs was significantly attenuated when NCOA2 was silenced. NCOA1 plays a necessary role in E 2 -induced CXCL12 expression and NCOA2 is required for P 4 to inhibit the E 2 -induced CXCL12 production in normal and ectopic endometrium.

Loss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration

“…26 Estradiol stimulates CXCL12 production and progesterone to inhibit this stimulation. 27,28 In vitro, AMD3100 blocked the CXCL12-mediated proliferative effects on epithelial cells. 29 Acute treatment of experimental endometriosis in mice with AMD3100 significantly decreases lesion volume and reduces BM cell trafficking to lesions.…”

NCOA1 (Nuclear receptor coactivator 1)

“…Endometriosis (EMS; ectopic endometrium) is an estrogen-dependent and inflammatory complex disease where immunological factors and angiogenesis play a pivotal role in its pathogenesis (Gazvani and Templeton, 2006;Rizner 2009). Shi et al showed that the expression of NCOA1 was greater in ectopic endometrium than that of normal endometrium, and NCOA1 was involved in the expression of stromal cell-derived factor 1 (SCDF1/CXCL12) whose expression was induced by estradiol (Shi et al, 2014).…”

Endometrial stromal cell attachment and matrix homeostasis in abdominal wall endometriomas

“…Unlike normal ESCs, progesterone did not alter increased expression of these matrix molecules in endometrioma-derived SCs. Some of this insensitivity to progesterone may be due to a number of factors including decreased PR levels, increased progesterone metabolism (Bulun et al, 2006(Bulun et al, , 2010 changes in cell-specific coactivators/repressors (Suzuki et al, 2010;Shi et al, 2014;Zelenko et al, 2012).…”