Hattori M A, Yoshino E, Shinohara Y, Horiuchi R, Kojima I
Department of Cell Biology, Gunma University, Japan.
J Mol Endocrinol. 1995 Dec;15(3):283-91. doi: 10.1677/jme.0.0150283.
It is well known that epidermal growth factor (EGF) induces down-regulation of LH receptors and desensitization to gonadotrophin stimulation in gonadal cells, including granulosa cells. In a previous study we showed that EGF receptor levels in rat granulosa cells were increased up to fourfold after 96 h of culture with human GH in the presence of FSH, and the present study has evaluated the action of EGF on these cells. The induced EGF receptors were identical in size to the pre-existing receptors as assessed by affinity labelling with 125I-EGF. After 48 h in culture, various amounts of EGF (0.5-10 ng) were added and the cells were cultured for a further 48 h. The addition of EGF caused down-regulation of LH receptors in cells expressing high levels of EGF receptors. However, this down-regulation was less than that in control cells. After the cells were washed, cAMP synthesis in response to human chorionic gonadotrophin (hCG) increased by two to three times the control value and this increase was closely correlated with an increase in EGF receptor content. However, stimulation with cholera toxin or forskolin showed no such augmentation, indicating that it may not be due to quantitative alterations in G proteins and their effector systems. Induction of EGF potentiation required long-term exposure to EGF, for at least more than 24 h. In addition, progesterone synthesis was sensitive to stimulation with lower doses of hCG. These findings indicate that the activation of hGH-induced EGF receptors may potentiate gonadotrophin action in granulosa cells.
众所周知，表皮生长因子（EGF）可诱导包括颗粒细胞在内的性腺细胞中促黄体生成素（LH）受体下调，并使其对促性腺激素刺激产生脱敏作用。在先前的一项研究中，我们发现，在促卵泡激素（FSH）存在的情况下，用人生长激素（hGH）培养大鼠颗粒细胞96小时后，其表皮生长因子受体水平增加了四倍，并且本研究评估了表皮生长因子对这些细胞的作用。通过用125I-表皮生长因子进行亲和标记评估，诱导产生的表皮生长因子受体在大小上与预先存在的受体相同。培养48小时后，加入不同量的表皮生长因子（0.5 - 10纳克），并将细胞再培养48小时。添加表皮生长因子导致表达高水平表皮生长因子受体的细胞中促黄体生成素受体下调。然而，这种下调程度小于对照细胞。细胞洗涤后，对人绒毛膜促性腺激素（hCG）的反应中，环磷酸腺苷（cAMP）合成增加至对照值的两到三倍，并且这种增加与表皮生长因子受体含量的增加密切相关。然而，用霍乱毒素或福斯高林刺激则未显示出这种增强作用，表明这可能不是由于G蛋白及其效应系统的数量改变所致。表皮生长因子增强作用的诱导需要长期暴露于表皮生长因子，至少超过24小时。此外，孕酮合成对较低剂量的人绒毛膜促性腺激素刺激敏感。这些发现表明，hGH诱导的表皮生长因子受体的激活可能增强颗粒细胞中促性腺激素的作用。
