In vitro effects of endothelin-1 on the contractility of myometrium obtained from pre- and postmenopausal women

Abstract

This study was conducted to evaluate the responsiveness of human nonpregnant myometrium to endothelin 1 (ET1) (10 10 M-10 6 M) and KCl (80 mM) in relation to the hormonal profile of the women, who were allocated into three groups: group 1, premenopausal follicular phase, n=14, group 2, premenopausal luteal phase, n=20, and group 3, postmenopausal women, n=12. At a concentration of 10 6 M, ET1 in both groups 1 and 2 induced very low ripples of high frequency (group 1: 80 14%, n=5, group 2: 314 63%, n=11; P<0·05 compared with the pretreatment frequency) which lasted significantly longer in group 2 (29 2 min, n=10, P<0·05) than in group 1 (20 2 min, n=5), increasing the basal tone (group 1: 57·9 6%, n=5, group 2: 64·4 4%, n=6), the amplitude of myometrial contractility (group 1: 1·2 0·07 g, n=5, group 2: 1·6 0·1 g, n=7, P<0·05) and the area under the contractility curve (AUC; group 1: 8·4 1·1 g min, n=6, group 2: 11·9 1·6 g min, n=11). In group 3, ET1 (10 6 M) created a sustained long-lasting contraction (initial phase: 43 6 min, n=6) characterized by the complete obliteration of spontaneous contractility with no ripples at all, and increasing significantly (P<0·05) the amplitude of myometrial contractility (2·8 0·5 g, n=6), the AUC (24·7 3·3 g min, n=6), as well as the basal tone (183·6 21%, n=6) compared with the two premenopausal groups. In all three groups KCl exposure induced an initial rise (mean amplitude value: 1·1 g) followed by a relaxation phase to the primal baseline level (mean duration value: 12 min). Addition of ET1 (10 6 M) to KCl (80 mM) induced a similar pattern of contractility to that evoked by ET1 alone which, compared with KCl alone lasted significantly longer (P<0·05) in all three groups (group 1: 20 2 min, n=6; group 2: 23 2 min, n=6; group 3: 35 3 min, n=5). In group 3, the percentage change in basal tone was significantly smaller following KCl than after the combination of KCl plus ET1 (149 16%, n=5; P<0·01), indicating a different mechanism of contractility between KCl and ET1. These results demonstrate for the first time differences in myometrial response to ET1 between pre-and postmenopausal women. It is suggested that KCl and ET1 affect uterine contractility through different mechanisms and that ovarian steroids may play a regulatory role in human uterine responsiveness to ET1.

What do we know about what happens to myometrial function as women age?

“…Of note also, contractility although low, is maintained well into post-menopause. This is consistent with an earlier in vitro study which had found spontaneous activity in post-menopausal women (Domali et al 2001). These latter authors also demonstrated responsiveness to endothelin 1, which could be modified by ovarian steroids.…”

“…One might assume that following the menopause, uterine activity ceases. However, rhythmical myometrial contractions have been seen by ultrasound examination in postmenopausal women (de Vries et al 1990) and one previous study has reported low levels of spontaneous activity in strips from human post-menopausal myometrium in vitro (Domali et al 2001). …”

Effect of Gonadal Hormones on Colonic Contractile Activity in Albino Rats

“…The amplitude of the spontaneous contractions was chosen because it expresses the contractile potential of each colonic strip. The change in basal tone was calculated using the formula: χ=β/α х 100 [19], where χ is the percentage change in the basal tone, α is the mean amplitude of the spontaneous colonic contractions, and β is the mean values of the distance of the lower parts of the induced contractions from the curve initial baseline.…”

Μηχανισμοί Συσταλτικής Ανταποκρισιμότητας Του Μυομητρίου Στη Δράση Της Προγεστερόνης Και Της Ενδοθηλίνης

“…Έτσι παρατηρείται µείωση της ανταπόκρισης του µυοµητρίου στην ωκυτοκίνης παρουσία οιστραδιόλης , όπως και µείωση της έντασης της ανταπόκρισης στη δράση της ΕΤ 1 παρουσία προγεστερόνης ωστόσο δεν έχουν διευκρινιστεί ακριβώς οι βιοχηµικές οδοί µέσω των οποίων πραγµατοποιούνται αυτές οι αλλαγές (Fu et al 1996, Phaneuf et al 1997,Fomin et al 1999, Domali et al 2001 Τα κριτήρια επιλογής των γυναικών για να συµπεριληφθούν στο πειραµατικό πρωτόκολλο ήταν:…”

“…Μελέτες που γίνανε σε µυοµήτριο προ και µετεµµηνοπαυσιακών γυναικών, έδειξαν ότι το ορµονικό προφίλ τροποποιεί τη συσταλτική ανταποκρισιµότητα του µυοµητρίου στη δράση της ΕΤ 1 (Domali et al 2001). Στην οµάδα της εµµηνόπαυσης η δράση της ΕΤ 1 είναι µεγαλύτερης διάρκειας και η προγεστερόνη έχει ανασταλτική δράση στην από την ΕΤ 1 προκαλούµενη συστολή.…”