In vitro responsiveness of human post-menopausal myometrium to endothelin-1 and ovarian steroids

It has been shown in vitro that endothelin 1 (ET1) differentially affects the human myometrial contractility according to the hormonal profile of women. Our purpose was to test the hypothesis that ovarian steroids influence the ET1 induced myometrial contractility. We performed three types of experiments. Myometrial tissues were exposed to 17beta-oestradiol (E), progesterone (P), E plus P (E+P) in concentrations 10(-10)M, 10(-8)M, 10(-7)M, 10(-6)M and 10(-4)M (Type I), ET1 in concentrations 10(-10)M, 10(-9)M, 10(-8)M, 10(-7)M and 10(-6)M (Type II) and E+ET1, P+ET1 and E+P+ET1 in concentrations ranging from 10(-10)M to 10(-6)M (Type III). Tissue exposure to E, P and E+P did not significantly alter the pattern of spontaneous myometrial motility. ET1 (10(-6)M) induced a sustained long-lasting contraction, the initial part of which lasted 34 +/- 4 min, elevating the initial baseline by 190 +/- 20%. This was followed by ripples of gradually increasing amplitude with no regular contractions up to the end of the period of observation (120 min). Addition of P or E+P to ET1 markedly restricted (p<0.05) the elevation of initial baseline (P+ET1: 68 +/- 8%, P+E+ET1: 67 +/- 8%), and significantly shortened (p<0.01) the duration of the alterations (P+ET1: 21 +/- 3 min, P+E+ET1: 26 +/- 3 min). These results demonstrate the lack of any significant effect of E and P or their combinations on the pattern of spontaneous myometrial motility in post-menopausal women. However, P alone or in combination with E exerted an inhibitory action on ET1 -induced contractility on human post-menopausal myometrium. The physiological significance of these findings remains to be clarified.