Hattori M A, Shinohara Y, Yoshino E, Kanzaki M, Kojima I, Horiuchi R
Institute of Endocrinology, Gunma University, Japan.
J Endocrinol. 1994 Jul;142(1):69-75. doi: 10.1677/joe.0.1420069.
The effect of human GH (hGH) on the regulation of epidermal growth factor (EGF) receptor was investigated during differentiation of FSH-treated rat granulosa cells, which has been reported to be mediated by a cAMP-dependent mechanism. By measuring the binding of [125I]iodo-EGF to the intact cells, FSH was shown to cause increases in the number of EGF binding sites after culture for 72 h. When granulosa cells were cultured with hGH, the number of FSH-induced EGF binding sites was augmented, with a half-maximal effect at about 10 micrograms hGH/l and a maximal stimulatory concentration of 100 micrograms/l. The stimulatory effect of hGH was absolutely dependent on insulin which by itself showed stimulatory effects on EGF binding sites. Scatchard analysis of EGF binding sites indicated that treatment with hGH increased the number of EGF binding sites (17,200 sites/cell after treatment with FSH; 31,700 sites/cell after FSH plus hGH), but did not alter the binding affinity. The augmentation was observed after culturing for 48 h and increased progressively with time, reaching 280% of the level after FSH treatment by 120 h. Although progesterone synthesis was increased by hGH, the markers of cell differentiation such as cAMP synthesis and LH binding sites were suppressed, indicating hGH inhibition of the cAMP-mediated signal. The action of hGH on the EGF binding sites was not accompanied by cell proliferation. These findings indicate that hGH has a novel action on the regulation of rat granulosa cell EGF binding sites and that the granulosa cell may possess both cAMP-dependent and -independent mechanisms for expression of EGF binding sites.
在促卵泡激素（FSH）处理的大鼠颗粒细胞分化过程中，研究了人生长激素（hGH）对表皮生长因子（EGF）受体调节的影响，据报道该过程由环磷酸腺苷（cAMP）依赖性机制介导。通过测量[125I]碘-EGF与完整细胞的结合，发现FSH在培养72小时后可使EGF结合位点数量增加。当颗粒细胞与hGH一起培养时，FSH诱导的EGF结合位点数量增加，在约10微克hGH/升时达到最大效应的一半，最大刺激浓度为100微克/升。hGH的刺激作用绝对依赖于胰岛素，胰岛素本身对EGF结合位点也有刺激作用。对EGF结合位点的Scatchard分析表明，hGH处理增加了EGF结合位点的数量（FSH处理后为17,200个位点/细胞；FSH加hGH处理后为31,700个位点/细胞），但未改变结合亲和力。培养48小时后观察到增加，并随时间逐渐增加，到120小时时达到FSH处理后水平的280%。尽管hGH增加了孕酮的合成，但细胞分化标志物如cAMP合成和促黄体生成素（LH）结合位点受到抑制，表明hGH抑制了cAMP介导的信号。hGH对EGF结合位点的作用不伴随细胞增殖。这些发现表明，hGH对大鼠颗粒细胞EGF结合位点的调节具有新作用，并且颗粒细胞可能具有cAMP依赖性和非依赖性机制来表达EGF结合位点。
