ENDOTHELIN IN THE HUMAN UTERUS DURING PREGNANCY

In this study we report the immunolocalization, binding and biological activity of endothelins in the human uterus. Since, in previous studies in the rabbit, sex steroids greatly affected uterine endothelin-1 (ET-1) immunolocalization and binding, we sought to compare results obtained in a relatively steroid-deprived uterus (postmenopausal women) with those obtained in late pregnancy. Two classes of ET receptors were identified in human pregnant and non-pregnant myometrium. One site (ET(B)) was a low capacity site (0.3 pM/mg protein) that bound with high affinity (0.1 nM), yet no selectivity, ET-1, ET-2, ET-3, sarafotoxin (SRTX) and vasoactive intestinal contractor (VIC). The second site (ET(A)) was six fold more concentrated than the former (1.9 pM/mg protein) and was relatively selective for ET-1, ET-2 and VIC but showed lower affinity for ET-3 and SRTX. Studies with human myometrial cells indicated that the ET(A) receptor mediates an increase in intracellular calcium, while the physiological function of the ET(B) receptor is still unclear. Homologous competition curves for ET-1 were used in order to study the ET receptor density (ET(A)+ET(B)) in individual myometrial samples. We found that the concentration of ET receptors did not change during different stages of labour or in postmenopausal women. We identified cells with intense positivity for ET-1 in human decidua. Similar cells were also present in pregnant myometrium, intimately associated with smooth muscle cells. Conversely, no staining for ET-1 was observed in non-pregnant myometrium. A paracrine role for ET-1 in the human uterus is suggested.