Musicki B, Aten R F, Behrman H R
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
Endocrinology. 1990 Mar;126(3):1388-95. doi: 10.1210/endo-126-3-1388.
Protein kinase-C (PKC) has been suggested as a possible mediator of the antigonadotropic action of prostaglandin F2 alpha (PGF2 alpha) in luteal cells. To examine this possibility, we evaluated the effects of phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] in relation to those of PGF2 alpha on cAMP accumulation and ATP levels as well as on the subcellular distribution of PKC activity in rat luteal cell cultures. Treatment of luteal cells for 1 h with TPA or PGF2 alpha produced a dose-dependent inhibition of LH-stimulated cAMP accumulation. Maximal inhibition produced by PGF2 alpha was about 35% greater than that produced by TPA. Moreover, PGF2 alpha produced a further inhibition of LH action when the cells were maximally inhibited by TPA. Staurosporine, a PKC inhibitor, reversed inhibition of LH-dependent cAMP accumulation produced by TPA, but had no effect on the response to PGF2 alpha. Furthermore, cells in which PKC was persistently activated by prolonged TPA treatment lost their responsiveness to additional TPA, but continued to show inhibition of cAMP accumulation by PGF2 alpha. TPA also produced a dose-dependent decrease in cell levels of ATP in contrast to PGF2 alpha. Finally, TPA produced a rapid redistribution of PKC activity from the cytosolic to the particulate fraction, whereas PGF2 alpha produced only a slight redistribution. We conclude that the acute antigonadotropic action of PGF2 alpha in rat luteal cells occurs via mechanisms other than phorbol ester-sensitive PKC activation.
蛋白激酶 C（PKC）被认为可能是前列腺素 F2α（PGF2α）在黄体细胞中抗促性腺激素作用的介质。为了检验这种可能性，我们评估了佛波酯[12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）]与 PGF2α对大鼠黄体细胞培养物中 cAMP 积累、ATP 水平以及 PKC 活性亚细胞分布的影响。用 TPA 或 PGF2α处理黄体细胞 1 小时，会产生对促黄体生成素（LH）刺激的 cAMP 积累的剂量依赖性抑制。PGF2α产生的最大抑制作用比 TPA 产生的约大 35%。此外，当细胞被 TPA 最大程度抑制时，PGF2α会进一步抑制 LH 的作用。PKC 抑制剂星形孢菌素可逆转 TPA 对 LH 依赖性 cAMP 积累的抑制作用，但对 PGF2α的反应没有影响。此外，经长时间 TPA 处理使 PKC 持续激活的细胞对额外的 TPA 失去反应性，但对 PGF2α抑制 cAMP 积累的作用仍有反应。与 PGF2α相反，TPA 还使细胞内 ATP 水平呈剂量依赖性下降。最后，TPA 使 PKC 活性从胞质迅速重新分布到颗粒部分，而 PGF2α仅产生轻微的重新分布。我们得出结论，PGF2α在大鼠黄体细胞中的急性抗促性腺激素作用是通过不同于佛波酯敏感的 PKC 激活的机制发生的。
