Endothelin-1 gene expression and protein biosynthesis in human endometrium: potential modulator of endometrial blood flow.

We present evidence that endothelin-1 (ET-1) is produced by two distinct cell types (other than vascular endothelial cells) in human endometrial tissue. The supportive findings of this investigation are summarized as follows: 1) prepro-ET-1 mRNA is present in endometrial tissue and in separated endometrial stromal and glandular epithelial cells in culture; 2) immunoreactive ET is secreted into the medium of isolated endometrial stromal cells and glandular epithelium maintained in culture; and 3) the level of prepro-ET-1 mRNA in endometrial tissues obtained at the premenstrual-menstrual phase of the endometrial cycle is greater than that in tissues from the proliferative or early and midsecretory phases. We also found that transforming growth factor-beta and interleukin-1 alpha act to increase the levels of prepro-ET-1 mRNA in endometrial stroma cells in monolayer culture. We speculate that ET-1 derived from endometrial stromal cells may act on the adventitial surface of contiguous spiral arterioles of the endometrium to modulate endometrial blood flow.