Antagonistic interactions of transforming growth factors in the regulation of granulosa cell differentiation.
Antagonistic interactions of transforming growth factors in the regulation of granulosa cell differentiation.
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DOI：
10.1210/endo-119-4-1879
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发表时间：
1986-10
期刊：
影响因子：
4.8
通讯作者：
E. Adashi;C. Resnick
中科院分区：
文献类型：
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作者：
E. Adashi;C. Resnick
在体外原代培养中，研究了转化生长因子（tgf）在获取颗粒细胞芳香酶活性中的作用，这些颗粒细胞来自未成熟的二乙基苯乙烯酚处理的大鼠。通过产生放射免疫可测定的雌激素来评估，基础芳香酶活性可以忽略不计，TGF α或TGF β在10 ng/ml剂量水平下对其没有影响。虽然用FSH治疗会显著增加芳化程度，但同时用TGF β (0.01-10 ng/ml)治疗会导致FSH效果的剂量依赖性增强，明显的中位有效剂量为224 +/- (SE) 32 pg/ml（约9 pM），最大效果比单独用FSH诱导的效果高3.6倍。相比之下，TGF - α (0.01-10 ng/ml)联合治疗可导致FSH作用的剂量依赖性衰减，表观中位抑制剂量为330 +/- (SE) 40 pg/ml（约60 pM），最大抑制效果为91 +/- (SE) 2%。然而，用相同（10 ng/ml）最大有效剂量的两种tgf联合治疗，对fsh刺激的雌激素积累几乎没有影响，这表明这些肽的相互中和作用是相反的。进一步对TGF - β的拮抗作用进行评价，发现其具有剂量依赖性，最大有效剂量TGF - α (10 ng/ml)部分克服了较低浓度（小于0.3 ng/ml）而不较高浓度（大于1 ng/ml） TGF - β对芳香化酶活性的刺激，从而使TGF - β的剂量-反应曲线向右移动。TGF对颗粒细胞DNA含量、合成、电镀效率和活力均无显著影响。综上所述，这些发现表明，外源提供的皮摩尔浓度的TGF - α对颗粒细胞芳香化酶活性的获得具有有效但截然相反的影响，并且这两种多肽之间的相互作用本质上是拮抗的。我们的研究结果进一步表明，tgf的这些直接细胞分化作用可能代表了这些肽的内在新特性，不同于它们在细胞生长调节中的既定作用。
The role of transforming growth factors (TGFs) in the acquisition of granulosa cell aromatase activity was investigated in vitro in a primary culture of granulosa cells harvested from immature, diethylstilbestrol-treated rats. Basal aromatase activity, as assessed by the generation of radioimmunoassayable estrogen, was negligible, remaining unaffected by treatment with either TGF alpha or TGF beta applied by themselves at the 10 ng/ml dose level. Whereas treatment with FSH produced a substantial increase in the extent of aromatization, concurrent treatment with TGF beta (0.01-10 ng/ml) resulted in dose-dependent augmentation of the FSH effect with an apparent median effective dose of 224 +/- (SE) 32 pg/ml (ca. 9 pM), and a maximal effect 3.6-fold greater than that induced by FSH alone. In contrast, concomitant treatment with TGF alpha (0.01-10 ng/ml) resulted in dose-dependent attenuation of FSH action with an apparent median inhibitory dose of 330 +/- (SE) 40 pg/ml (ca. 60 pM), and a maximal inhibitory effect of 91 +/- (SE) 2%. However, combined treatment with identical (10 ng/ml) maximally effective doses of both TGFs had little or no effect on the FSH-stimulated accumulation of estrogen, suggesting mutual neutralization by the opposing actions of these peptides. Further evaluation of the antagonistic interaction of the TGFs revealed it to be dose-dependent in that maximally effective doses of TGF alpha (10 ng/ml) partially overcame the stimulation of aromatase activity brought about by relatively low (less than 0.3 ng/ml) but not higher (greater than 1 ng/ml) concentrations of TGF beta, thereby shifting the TGF beta dose-response curve to the right. Treatment with either TGF had no significant effect on granulosa cell DNA content or synthesis, plating efficiency or viability. Taken together, these findings suggest that picomolar concentrations of exogenously provided TGF alpha TGF beta exert potent but diametrically opposed effects on the acquisition of granulosa cell aromatase activity and that the interaction between these two peptides is antagonistic in nature. Our findings further suggest that these direct cytodifferentiative effects of the TGFs may represent intrinsic novel properties of these peptides distinct from their well-established role in the regulation of cellular growth.