Knecht M, Feng P, Catt K
Endocrinology. 1987 Apr;120(4):1243-9. doi: 10.1210/endo-120-4-1243.
Regulatory actions of transforming growth factor-beta (TGF beta) on granulosa cell function were analyzed in cells cultured from the ovaries of diethylstilbestrol-implanted rats. In the presence of a suboptimal concentration of FSH (5 ng/ml) that increased LH receptors by 100-fold during a 72-h culture, TGF beta augmented this response in a dose-dependent manner with a maximal effect at 16 pM. In contrast, the growth factor inhibited the LH receptor response to an optimal dose of FSH (50 ng) by up to 50% and was inactive in the absence of gonadotropin. TGF beta also enhanced the formation of cAMP by 5 ng FSH and partially inhibited the effects of higher FSH concentrations. However, the actions of TGF beta were more prominent on LH receptor induction than on cAMP production with either low or high amounts of FSH. In addition, TGF beta had little effect on cAMP production stimulated by cholera toxin or forskolin, but amplified the actions of these ligands as well as that of 8-bromo-cAMP on LH receptor expression. TGF beta also modulated the steroidogenic activity of the granulosa cells, with increased production of progesterone in response to 5-100 ng FSH. The bifunctional actions of TGF beta on FSH-induced LH receptor formation were observed throughout a 96-h culture period. However, the presence of the growth factor was not required for the first 24 h of culture, indicating that TGF beta alters the later events involved in LH receptor formation. TGF beta augmented the stimulatory actions of 5 ng FSH on LH receptors in the absence or presence of insulin, but its inhibitory effect on these receptors was only observed in cells treated with insulin. These results indicate that TGF beta modifies FSH action during granulosa cell development in a biphasic manner. TGF beta can exert stimulatory or inhibitory effects depending upon the concentration of FSH and the presence of insulin, and these are due to alterations in cAMP action as well as cAMP production. Autocrine and/or endocrine actions of TGF beta during granulosa cell differentiation may be involved in the processes of follicle selection and development.
在从己烯雌酚植入大鼠卵巢培养的细胞中，分析了转化生长因子-β（TGF-β）对颗粒细胞功能的调节作用。在亚最佳浓度的促卵泡激素（FSH，5 ng/ml）存在下，该浓度在72小时培养期间使促黄体生成素（LH）受体增加了100倍，TGF-β以剂量依赖方式增强了这种反应，在16 pM时达到最大效应。相反，生长因子抑制LH受体对最佳剂量FSH（50 ng）的反应高达50%，并且在无促性腺激素时无活性。TGF-β还增强了5 ng FSH诱导的环磷酸腺苷（cAMP）形成，并部分抑制了更高FSH浓度的作用。然而，无论FSH量低或高，TGF-β对LH受体诱导的作用比对cAMP产生的作用更显著。此外，TGF-β对霍乱毒素或福斯高林刺激的cAMP产生几乎没有影响，但增强了这些配体以及8-溴-cAMP对LH受体表达的作用。TGF-β还调节颗粒细胞的类固醇生成活性，对5-100 ng FSH的反应中孕酮产量增加。在整个96小时培养期内均观察到TGF-β对FSH诱导的LH受体形成的双功能作用。然而，培养的前24小时不需要生长因子存在，这表明TGF-β改变了LH受体形成过程中的后期事件。在存在或不存在胰岛素的情况下，TGF-β增强了5 ng FSH对LH受体的刺激作用，但其对这些受体的抑制作用仅在胰岛素处理的细胞中观察到。这些结果表明，TGF-β以双相方式改变颗粒细胞发育过程中的FSH作用。TGF-β可根据FSH浓度和胰岛素的存在发挥刺激或抑制作用，这是由于cAMP作用以及cAMP产生的改变所致。TGF-β在颗粒细胞分化过程中的自分泌和/或内分泌作用可能参与卵泡选择和发育过程。
