Search

It has been shown in vitrothat 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 17β-oestradiol (E), progesterone (P), E plus P (E+P) in concentrations 10t−10M, 10−8M, 10−7M, 10t−6M and 10−4M (Type I), ET1 in concentrations 10t−10M, 10−9M, 10−8M, 10−7M and 10t−6M (Type II) and E+ET1, P+ET1 and E+P+ET1 in concentrations ranging from 10−10M to 10−6M (Type III). Tissue exposure to E, P and E+P did not significantly alter the pattern of spontaneous myometrial motility. ET1 (10−6M) 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.

Leptin is a 16-kDa polypeptide, encoded in humans by the LEP gene. This protein is probably involved in the regulation of ovarian function, oocyte maturation and embryo development, and in the implantation process. During pregnancy, leptin is produced in the placenta; its values increase in the maternal blood particularly in the second trimester and decline postpartum. Leptin levels may be abnormally high in pregnancies complicated by conditions such as diabetes mellitus and pre-eclampsia. The role of leptin in fetal physiology has not been clarified, although cord blood values correlate significantly with birth weight. It is expected that further research will provide new insight into the physiological importance of leptin in the pregnant woman and fetus.

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 gxmin, n=6, group 2: 11.9+/-1.6 g x 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 x 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.