THE ENDOTHELIN-PARATHYROID HORMONE-RELATED PROTEIN VASOACTIVE PEPTIDESYSTEM IN HUMAN ENDOMETRIUM - MODULATION BY TRANSFORMING GROWTH-FACTOR-BETA

Endothelin-1 (ET-1), a potent vasoconstrictor, and parathyroid hormone -related protein (PTH-rP), a potent vasorelaxant, are present and synt hesized in human endometrium, The production of these vasoactive pepti des in stromal cells of the human endometrium is modulated by sex ster oid hormones, In addition, neutral endopeptidase 24.11 (also called en kephalinase), which degrades ET-1, is expressed in the stromal cells o f the endometrium, and the levels of this enzyme (mRNA, protein and sp ecific activity) are increased in response to progesterone/progestin. The sex steroid hormone-mediated regulation of vasoactive peptide form ation and action in the human endometrium is believed to serve a key r ole in modulating spiral artery tone/blood flow and thus endometrial b leeding, whether progestin induced or naturally occurring, Moreover, t he expression of ET-1, PTB-rP and enkephalinase is modulated by transf orming growth factor-beta, We hypothesize that the inappropriate expre ssion of ET-1, enkephalinase and PTH-rP in endometrial stromal cells d uring synthetic progestin administration may be one cause of abnormal endometrial development and erratic endometrial bleeding.