Effects of endothelin-I on the function of the cultured granulosa sells

本研究旨在探讨内皮素-1(ET-1)对猪中、小卵泡颗粒细胞功能的直接影响。培养的猪颗粒细胞呈ET-I样免疫反应阳性(ET-1-LI)，Northern印迹分析证实这些细胞表达前ET-1的信使RNA。结合研究表明，存在非选择性的单一结合部位，主要包括ET_B亚型。刺激周期患者卵泡液中ET-1-LI水平升高。在短期孵育(2小时)中，ET-1促进基础孕酮和FSH刺激的孕酮分泌，而在长期孵育(48小时)中，ET-1抑制FSH和hCG刺激的孕酮积累。ET-1可显著增加细胞DNA合成。这些生物学作用是由ET-1诱导的，可能是通过cAMP-蛋白激酶A途径和细胞内钙动员-蛋白激酶C途径。结果提示，ET-1对猪颗粒细胞功能具有自分泌/旁分泌作用，人早孕蜕膜细胞可合成和释放ET-1，并具有与磷脂酰肌醇降解作用相偶联的ET-1受体。提示ET-1在人蜕膜细胞中可能具有潜在的自分泌和/或旁分泌功能。

This study was conducted to investigate whether endothelin-1 (ET-1) has direct effects on the functions of porcine granulosa cells harvested from small or medium follicles. The positive ET-I-like immunoreactivity (ET-1-LI) was observed in the cultured porcine granulosa cells, and Northern blot analysis demonstrated the expression of messenger RNA for prepro-ET-1 in these cells. THe binding study showed the presence of non-selective, single class of binding sites which included subtype of ET_B, predominantly. Increased ET-1-LI was detected in the human follicular fluid obtained from the patients in stimulated ovarian cycles. ET-1 stimulated basal and FSH-stimulated secretion of progesterone during short term incubation (2 hrs), while it inhibited FSH- and hCG-stimulated accumulation of progesterone during long-term incubation (48 hrs) of immature or moderately mature granulosa cells. ET-1 significantly increased DNA synthesis in the cells. These biological actions were induced by ET-1, probably via cAMP - protein kinase A pathway and intracellular calcium mobilization - protein kinase C pathway. The results suggest that ET-1 exerts autocrine/paracrine effects on the porcine granulosa cell functions.Furthermore, the present study also demonstrates that human decidual cells in the early pregnancy can synthsize and release ET-1, and possess specific receptors for ET-1 functionally coupled to phosphoinositide breakdown. This suggests that ET-1 may have its potential autocrine and/or paracrine function in human decidual cells.