Down regulation of P21-activated kinase 1 (Pak1) by progestin and its increased expression in the eutopic endometrium of women with endometriosis

Abstract

OBJECTIVE: P21-activated kinase 1 (Pak1) is a well characterized serine/threonine kinase integrating various signaling pathways that are vital to normal cell survival and function. This study was performed to evaluate whether sex steroids may regulate the expression of Pak1 in the endometrial cells as well as whether its expression is increased in the eutopic endometrium of women with endometriosis.DESIGN: Experimental laboratory study.MATERIALS AND METHODS: Following in vitro estradiol (E2) and/or medroxyprogesterone acetate (MPA) treatment of Ishikawa cells as well as endometrial stromal cells, Pak1 expression was analyzed utilizing Western blot analysis and immunocytochemistry. Immunohistochemistry was performed in 31 control subjects and 29 women with endometriosis and Pak1 immunoreactivity was evaluated semiquantitatively.RESULTS: Although in vitro E2 treatment did not have any effect on Pak1 protein level in Ishikawa cells and endometrial stromal cells, in vitro E2 plus MPA and MPA treatment led to significant decrease of Pak1 expression in both cells (P<0.05; P<0.05, respectively). Immunohistochemical staining also revealed that Pak1 expression is significantly decreased during the secretory phase in the glandular cells and the stromal cells within the control subjects (P<0.001). The immunoreactivity of Pak1 in gladular cells was significantly increased in the eutopic endometrium of women with endometriosis compared to the control subjects during the secretory phase (P<0.01), and the main increase was obvious during the mid-secretory phase (P<0.01).CONCLUSIONS: These findings suggest that Pak1 is downregulated by progesterone during the secretory phase in normal endometrium and increased expression of Pak1 during the secretory phase might lead to establishment of endometriosis. OBJECTIVE: P21-activated kinase 1 (Pak1) is a well characterized serine/threonine kinase integrating various signaling pathways that are vital to normal cell survival and function. This study was performed to evaluate whether sex steroids may regulate the expression of Pak1 in the endometrial cells as well as whether its expression is increased in the eutopic endometrium of women with endometriosis. DESIGN: Experimental laboratory study. MATERIALS AND METHODS: Following in vitro estradiol (E2) and/or medroxyprogesterone acetate (MPA) treatment of Ishikawa cells as well as endometrial stromal cells, Pak1 expression was analyzed utilizing Western blot analysis and immunocytochemistry. Immunohistochemistry was performed in 31 control subjects and 29 women with endometriosis and Pak1 immunoreactivity was evaluated semiquantitatively. RESULTS: Although in vitro E2 treatment did not have any effect on Pak1 protein level in Ishikawa cells and endometrial stromal cells, in vitro E2 plus MPA and MPA treatment led to significant decrease of Pak1 expression in both cells (P<0.05; P<0.05, respectively). Immunohistochemical staining also revealed that Pak1 expression is significantly decreased during the secretory phase in the glandular cells and the stromal cells within the control subjects (P<0.001). The immunoreactivity of Pak1 in gladular cells was significantly increased in the eutopic endometrium of women with endometriosis compared to the control subjects during the secretory phase (P<0.01), and the main increase was obvious during the mid-secretory phase (P<0.01). CONCLUSIONS: These findings suggest that Pak1 is downregulated by progesterone during the secretory phase in normal endometrium and increased expression of Pak1 during the secretory phase might lead to establishment of endometriosis.