PRODUCTION AND CHARACTERIZATION OF ENDOTHELIN RELEASED BY HUMAN ENDOMETRIAL EPITHELIAL-CELLS IN CULTURE

This study identified and characterized endothelin (ET) produced by hu man endometrial epithelial cells cultured under serum-free conditions, compared the ET released by cells derived from proliferative and secr etory phase endometrium, and examined the regulation of ET released by these cells. ET messenger RNA was detected in normal human endometriu m with maximal expression in the mid-late secretory phase. Immunoreact ive ET released into culture media by separated endometrial epithelial and stromal cells was almost entirely of epithelial cell origin, cons istent with the previous immunohistochemical findings. This was identi fied as ET-1 by reverse phase high-pressure liquid chromatography, and the fractionated conditioned media exhibited bioactivity similar to t hat of standard ET-1. Mean ET production was greater from cells derive d from proliferative phase endometrium cultured either in serum (P < 0 .02) or serum-free conditions (P < 0.02). Fetal calf serum stimulated ET-1 production from epithelial cells in a dose-responsive manner. ET production was also stimulated by transforming growth factor-beta 1 (2 , 5 and 10 ng/mL) and IL-1 alpha (10 and 100 IU/mL) under serum-free c onditions but always to a lesser extent than stimulation by serum. The production of ET in human endometrium underlines a potential role for ET in endometrial function.