Soodak L K, Behrman H R
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
Endocrinology. 1988 Apr;122(4):1308-13. doi: 10.1210/endo-122-4-1308.
Adenosine markedly amplifies the response of isolated rat and human luteal cells to LH via an intracellular site of action that is associated with an increase in cell ATP levels. This effect of adenosine is maximal in midstage cells and minimal at the onset of functional regression in late stage luteal cells. The objective of the present studies was to evaluate the role of mitochondria in mediating the action of adenosine in isolated rat luteal cells and to assess whether mitochondrial function may be compromised in regressing luteal cells. The present studies show that adenosine produced a significant increase in luteal cell levels of ADP and ATP, but had no effect on cell levels of GTP. Since ADP stimulates oxidative phosphorylation, we evaluated the role of mitochondria in mediating the amplification of LH action by adenosine in luteal cells with two mitochondrial inhibitors, oligomycin and dinitrophenol. Both inhibitors markedly reduced, in a dose-dependent manner, LH-stimulated cAMP accumulation in the presence or absence of adenosine. In parallel, both inhibitors decreased basal and adenosine-elevated ATP levels in a dose-related manner. Although late stage luteal cells showed a marked reduction in adenosine amplification of LH-stimulated cAMP accumulation, no change in adenosine-dependent elevation of cell levels of ATP was seen. We conclude that amplification of LH action and elevation of ATP levels in midstage cells by adenosine requires an increase in oxidative phosphorylation that is stimulated by an increase in cell levels of ADP. However, attenuation of adenosine amplification of LH action in late stage luteal cells is not due to impaired ATP production.
腺苷通过与细胞ATP水平升高相关的细胞内作用位点，显著增强分离的大鼠和人黄体细胞对促黄体生成素（LH）的反应。腺苷的这种作用在中期细胞中最大，而在晚期黄体细胞功能衰退开始时最小。本研究的目的是评估线粒体在介导腺苷对分离的大鼠黄体细胞的作用中的作用，并评估线粒体功能在衰退的黄体细胞中是否可能受损。本研究表明，腺苷使黄体细胞中的ADP和ATP水平显著升高，但对细胞中的GTP水平没有影响。由于ADP刺激氧化磷酸化，我们用两种线粒体抑制剂寡霉素和二硝基酚评估了线粒体在介导腺苷对黄体细胞中LH作用的放大中的作用。在存在或不存在腺苷的情况下，两种抑制剂均以剂量依赖性方式显著降低LH刺激的cAMP积累。同时，两种抑制剂均以剂量相关方式降低基础和腺苷升高的ATP水平。尽管晚期黄体细胞中腺苷对LH刺激的cAMP积累的放大作用显著降低，但未观察到腺苷依赖性细胞ATP水平升高的变化。我们得出结论，腺苷对中期细胞中LH作用的放大和ATP水平的升高需要氧化磷酸化的增加，而氧化磷酸化的增加是由细胞中ADP水平的增加所刺激的。然而，晚期黄体细胞中腺苷对LH作用放大的减弱并非由于ATP产生受损。
