GLUCOCORTICOID-STIMULATED UTILIZATION OF SUBSTRATES IN HEPATIC MITOCHONDRIA
GLUCOCORTICOID-STIMULATED UTILIZATION OF SUBSTRATES IN HEPATIC MITOCHONDRIA
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DOI：
10.1016/0003-9861(77)90466-0
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发表时间：
1977-01-01
影响因子：
3.9
通讯作者：
HAYNES, RC
中科院分区：
文献类型：
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作者：
WAKAT, DK;HAYNES, RC
给予大鼠糖皮质激素可通过随后分离的肝线粒体刺激底物的利用率。这种刺激存在于丙酮酸的羧化和脱羧化以及β-羟基丁酸酯和琥珀酸在状态3和去偶联条件下的氧化。这些效应是由皮质醇、曲安奈德和地塞米松产生的，但不是由脱氧皮质酮产生的。对类固醇的反应与给予胰高血糖素或三碘甲腺原氨酸[T3]后观察到的相似。丙酮酸脱羧化速率的刺激与丙酮酸羧化速率无关。类固醇在体内给药后刺激新陈代谢发生的时间以及达到最大刺激水平所需的时间各不相同。皮质醇-琥珀酸酯作用60min内和地塞米松或皮质醇作用90min内刺激作用明显。治疗2~4h后刺激最大。在地塞米松或皮质醇处理后，线粒体反应的剂量依赖性表现为丙酮酸羧化速率的增加。在测试的两种类固醇中，地塞米松在增加线粒体活性方面的效力大约是皮质醇的2000倍。高血糖素作用30min或T3作用20h的作用与糖皮质激素的刺激作用相加。丙酮酸羧化速率的增加是完全相加的，而底物的氧化大约是75%的相加。
Glucocorticoids administered to rats stimulate the rates of utilization of substrates by subsequently isolated hepatic mitochondria. This stimulation was observed in the carboxylation and decarboxylation of pyruvate and in the oxidation of .beta.-hydroxybutyrate and succinate during state 3 and uncoupled conditions. These effects were produced by cortisol, triamcinolone and dexamethasone, but not by deoxycorticosterone. Responses to the steroids were similar to those observed after glucagon or triiodothyronine [T3] administration. The stimulation of the rate of pyruvate decarboxylation occurred independently of the rate of pyruvate carboxylation. Steroids varied with respect to the time required after in vivo administration for stimulation of metabolism to occur, as well as for achievement of maximally stimulated levels. Significant stimulation was obtained within 60 min after treatment with cortisol-succinate and 90 min after dexamethasone or cortisol. Maximal stimulation was observed after 2-4 h of treatment. The dose dependency of the mitochondrial responses was observable in the increase in the rates of pyruvate carboxylation after dexamethasone or cortisol treatment. Of the 2 steroids tested, dexamethasone was approximately 2000-fold more potent than cortisol in increasing mitochondrial activity. The effects of 30 min of treatment with glucagon or 20 h with T3 were additive with the stimulation produced by glucocorticoids. Complete additivity was found in the increased rates of pyruvate carboxylation, while oxidation of substrates was approximately 75% additive.